Podcasts about qalys

In this episode, we explore the complex and often debated concept of value in prescription drugs. They discuss how different stakeholders—payers, manufacturers, providers, regulators, and patients—define value, and how methodologies like health technology assessments (HTA) and cost-effectiveness analyses shape drug pricing and access. With insights from leading experts, the conversation examines the controversies surrounding value-based pricing, including the role of real-world evidence, quality-adjusted life years (QALYs), and innovation incentives. Can we strike a balance between affordability, innovation, and patient access? And what does the future hold for value-based drug pricing in the U.S.? Tune in for a deep dive into one of the most critical issues in healthcare today. Daniel Ollendorf, Chief Scientific Officer and Director of HTA Methods and Engagement Lou Garrison, Professor Emeritus at University of Washington CHOICE Institute for Clinical and Economic Review (ICER) FDA GLP-1 Drugs Medicare Biosimilars Generics Versus Biosimilars PBMs (Pharmacy Benefit Managers) 340B Drug Pricing Program Questions or comments?Email us at comments@prescriptionforbetteraccess.com.Find us on social media! Follow us on X, LinkedIn, YouTube and Threads.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: The Pearly Gates, published by lsusr on May 30, 2024 on LessWrong. St. Peter stood at a podium before the Gates of Heaven. The gates were gold, built on a foundation of clouds. A line of people curved and winded across the clouds, beyond what would be a horizon if this plane of existence was positively-curved. Instead, they just trailed away into Infinity, away from the golden wall securing Heaven. The worthy would enter eternal paradise. The unforgiven would burn in Hell for just as long. Infinite judgment for finite lives. "Next please," said St. Peter. The foremost man stepped forward. He had freckles and brilliant orange hair. "Tell me about yourself," said St. Peter. "Me name's Seamus O'Malley, sure, and I was - or still am, begorrah - an Irish Catholic," said Seamus. "How did you die?" said St. Peter. "Jaysus, I went and blew meself to bits tryin' to cobble together an auld explosive to give those English occupiers a proper boot, so I did," said Seamus. "You were a good Catholic," said St. Peter, "You're in." Seamus entered the Pearly Gates with his head held high. "Next please," said St. Peter. A Floridian woman stepped forward. "My name is Megan Roberts. I worked as a nurse. I couldn't bear to tell people their family members were going to die. I poisoned them so they would die when a less empathetic nurse was on watch," said the nurse. "That's a grave sin," said St. Peter. "But it's okay because I'm a Christian. Protestant," said Megan. "Did you go to church?" said St. Peter. "Mostly just Christmas and Easter," said Megan, "But moments before I died, I asked Jesus for forgiveness. That means my sins are wiped away, right?" "You're in," said St. Peter. "Next please," said St. Peter. A skinny woman stepped forward. "My name is Amanda Miller. I'm an Atheist. I've never attended church or prayed to God. I was dead certain there was no God until I found myself in the queue on these clouds. Even right now, I'm skeptical this isn't a hallucination," said Amanda. "Were you a good person?" asked St. Peter. "Eh," said Amanda, "I donated a paltry 5% of my income to efficient public health measures, resulting in approximately 1,000 QALYs." "As punishment for your sins, I condemn you to an eternity of Christians telling you 'I told you so'," said St Peter, "You're in." "Next please," said St. Peter. A bald man with a flat face stepped forward. "My name is Oskar Schindler. I was a Nazi," said Oskar. "Metaphorical Nazi or Neo-Nazi?" asked St Peter. "I am from Hildesheim, Germany. I was a card-carrying member of the Nazi Party from 1935 until 1945," said Oskar. "Were you complicit in the war or just a passive bystander?" asked St. Peter. "I was a war profiteer. I ran a factory that employed Jewish slave labor to manufacture munitions in Occupied Poland," said Oskar. "Why would you do such a thing?" asked St. Peter. "The Holocaust," said Oskar, "Nobody deserves that. Every Jew I bought was one fewer Jew in the death camps. Overall, I estimate I saved 1,200 Jews from the gas chambers." St. Peter waited, as if to say go on. "I hired as many workers as I could. I made up excuses to hire extra workers. I bent and broke every rule that got in my way. When that didn't work, I bought black market goods to bribe government officials. I wish I could have done more, but we do what we can with the limited power we have," said Oskar, "Do you understand?" St. Peter glanced furtively at the angels guarding the Gates of Heaven. He leaned forward, stared daggers into Oskar's eyes and whispered, "I think I understand you perfectly." "Next please," said St. Peter. A skinny Indian man stepped forward. "My name is Siddhartha Gautama. I was a prince. I was born into a life of luxury. I abandoned my duties to my kingdom and to my people," said Siddhartha. St. Peter read from his scroll. "It says ...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: The Pearly Gates, published by lsusr on May 30, 2024 on LessWrong. St. Peter stood at a podium before the Gates of Heaven. The gates were gold, built on a foundation of clouds. A line of people curved and winded across the clouds, beyond what would be a horizon if this plane of existence was positively-curved. Instead, they just trailed away into Infinity, away from the golden wall securing Heaven. The worthy would enter eternal paradise. The unforgiven would burn in Hell for just as long. Infinite judgment for finite lives. "Next please," said St. Peter. The foremost man stepped forward. He had freckles and brilliant orange hair. "Tell me about yourself," said St. Peter. "Me name's Seamus O'Malley, sure, and I was - or still am, begorrah - an Irish Catholic," said Seamus. "How did you die?" said St. Peter. "Jaysus, I went and blew meself to bits tryin' to cobble together an auld explosive to give those English occupiers a proper boot, so I did," said Seamus. "You were a good Catholic," said St. Peter, "You're in." Seamus entered the Pearly Gates with his head held high. "Next please," said St. Peter. A Floridian woman stepped forward. "My name is Megan Roberts. I worked as a nurse. I couldn't bear to tell people their family members were going to die. I poisoned them so they would die when a less empathetic nurse was on watch," said the nurse. "That's a grave sin," said St. Peter. "But it's okay because I'm a Christian. Protestant," said Megan. "Did you go to church?" said St. Peter. "Mostly just Christmas and Easter," said Megan, "But moments before I died, I asked Jesus for forgiveness. That means my sins are wiped away, right?" "You're in," said St. Peter. "Next please," said St. Peter. A skinny woman stepped forward. "My name is Amanda Miller. I'm an Atheist. I've never attended church or prayed to God. I was dead certain there was no God until I found myself in the queue on these clouds. Even right now, I'm skeptical this isn't a hallucination," said Amanda. "Were you a good person?" asked St. Peter. "Eh," said Amanda, "I donated a paltry 5% of my income to efficient public health measures, resulting in approximately 1,000 QALYs." "As punishment for your sins, I condemn you to an eternity of Christians telling you 'I told you so'," said St Peter, "You're in." "Next please," said St. Peter. A bald man with a flat face stepped forward. "My name is Oskar Schindler. I was a Nazi," said Oskar. "Metaphorical Nazi or Neo-Nazi?" asked St Peter. "I am from Hildesheim, Germany. I was a card-carrying member of the Nazi Party from 1935 until 1945," said Oskar. "Were you complicit in the war or just a passive bystander?" asked St. Peter. "I was a war profiteer. I ran a factory that employed Jewish slave labor to manufacture munitions in Occupied Poland," said Oskar. "Why would you do such a thing?" asked St. Peter. "The Holocaust," said Oskar, "Nobody deserves that. Every Jew I bought was one fewer Jew in the death camps. Overall, I estimate I saved 1,200 Jews from the gas chambers." St. Peter waited, as if to say go on. "I hired as many workers as I could. I made up excuses to hire extra workers. I bent and broke every rule that got in my way. When that didn't work, I bought black market goods to bribe government officials. I wish I could have done more, but we do what we can with the limited power we have," said Oskar, "Do you understand?" St. Peter glanced furtively at the angels guarding the Gates of Heaven. He leaned forward, stared daggers into Oskar's eyes and whispered, "I think I understand you perfectly." "Next please," said St. Peter. A skinny Indian man stepped forward. "My name is Siddhartha Gautama. I was a prince. I was born into a life of luxury. I abandoned my duties to my kingdom and to my people," said Siddhartha. St. Peter read from his scroll. "It says ...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Should I donate my kidney or part of my liver?, published by Bob Jacobs on April 11, 2024 on The Effective Altruism Forum. I've been talking with my hospital about donating my kidney and it's been going rather well. However, one piece of unfortunate news they told me is that I can't donate both my kidney and a piece of my liver (and that I can't do this in another hospital either). So people that want to donate are faced with a dilemma of which one to choose. I asked the doctors whether they had literature on this, but unfortunately they didn't know of any that compared the two. I've looked at some papers, and the side effects for both kidney donation and liver donation seem to be negligible for the donor (way less than 1 QALY). That leaves us with the question of what has the bigger impact for the recipient. I've looked for papers that compared them directly, but couldn't really find anything. It seems like for kidneys: The average donation buys the recipient about 5 - 7 extra years of life (beyond the counterfactual of dialysis). It also improves quality of life from about 70% of the healthy average to about 90%. Non-directed kidney donations can also help the organ bank solve allocation problems around matching donors and recipients of different blood types. Most sources say that an average donated kidney creates a "chain" of about five other donations, but most of these other donations would have happened anyway; the value over counterfactual is about 0.5 to 1 extra transplant completed before the intended recipient dies from waiting too long. So in total, a donation produces about 10 - 20 extra quality-adjusted life years. Liver donation seems to generate less QALYs, though the estimates vary a lot. So I'm currently leaning towards donating my kidney. Does anyone have any more insights into this? Does anyone know of an analysis that compares the two? (If someone is/wants to write one, I'd be glad to help) Please share your thoughts. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: University groups as impact-driven truth-seeking teams, published by anormative on March 14, 2024 on The Effective Altruism Forum. A rough untested idea that I'd like to hear others' thoughts about. This is mostly meant as a broader group strategy framing but might also have interesting implications for what university group programming should look like. EA university group organizers are often told to "backchain" our way to impact: What's the point of your university group? "To create the most impact possible, to do the greatest good we can" What do you need in order to create that? "Motivated and competent people working on solving the world's most pressing problems" And as an university group, how do you make those people? "Find altruistic people, share EA ideas with them, provide an environment where they can upskill" What specific things can you do to do that? "Intro Fellowships to introduce people to EA ideas, career planning and 1-1s for upskilling" This sort of strategic thinking is useful at times, but I think that it can also be somewhat pernicious, especially when it naively justifies the status quo strategy over other possible strategies.[1] It might instead be better to consider a wide variety of framings and figure out which is best.[2] One strategy framing I want to propose that I would be interested in testing is viewing university groups as "impact driven truth-seeking teams." What this looks like An impact-driven truth-seeking team is a group of students trying to figure out what they can do with their lives to have the most impact. Imagine a scrappy research team where everyone is trying to figure out the answer to this research question - "how can we do the most good?" Nobody has figured out the question yet, nobody is a purveyor of any sort of dogma, everyone is in it together to figure out how to make the world as good as possible with the limited resources we have. What does this look like? I'm not all that sure, but it might have some of these elements: An intro fellowship that serves an introduction to cause prioritization, philosophy, epistemics, etc. Regular discussions or debates about contenders for "the most pressing problem of our time" More of a focus on getting people to research and present arguments themselves than having conclusions presented to them to accept Active cause prioritization Live google docs with arguments for and against certain causes Spreadsheets attempting to calculate possible QALYs saved, possible x-risk reduction, etc Possibly (maybe) even trying to do novel research on open research questions No doubt some of the elements we identified before in our backchaining are imporant too - the career planning and the upskilling Testing fit, doing cheap tests, upskilling, getting experience I'm sure there's much more that could be done along these lines that I'm missing or that hasn't been thought of yet at all Another illustrative picture - imagine instead of university groups being marketing campaigns for Doing Good Better, we could each be a mini-80,000 hours research team,[3] trying to start at first principles and building our way up, assisted by the EA movement, but not constrained by it. Cause prio for it's own sake for the sake of EA Currently, the modus operandi of EA university groups seems to be selling the EA movement to students by convincing them of arguments to prioritize the primary EA causes. It's important to realize that the EA handbook serves as an introduction to the movement called Effective Altruism [4] and the various causes that it has already identified as being impactful, not as an introductory course in cause prioritization. It seems to me that this is the root of much of the unhealthy epistemics that can arise in university groups.[5] I don't think that students in my proposed team should sto...

Initially, this conversation focuses on how cost-effectiveness issues relate to the MASLD Disease Burden. In the process, Zobair Younossi provides education on some of the metrics and concepts pivotal to drug value assessment.Roger Green starts off asking how the economics of treating MASH stack up against hypercholesterolemia at the birth of statins in the 1980s, where the medical benefit was clear but economic was harder to manage. Zobair proceeds to describe the process by which the cost effectiveness of drugs is measured, computation of Quality Adjusted Life Years, or QALYs, and how different countries vary in the level of QALYs they consider cost effective. He also notes that within the US, at least, we may be willing to accept five times greater cost per QALY than for another. He also points out that cost effectiveness grows as new therapeutic options include price competition into a market.Louise Campbell shares the specific US cost numbers from Zobair's article, which she describes as “frightening,” particularly given the rate of growth in the disease and society's lack of efficacy in shifting the curve on this. Zobair responds by saying that one goal of the article was to create awareness that regular surveillance of diabetic patients for MASLD could have a significant economic impact in the US. As the conversation winds down, Jörn Schattenberg comments that all this is a team effort and Zobair agrees heartily.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Saving the world sucks, published by Defective Altruism on January 10, 2024 on LessWrong. I don't want to save the world. I don't want to tile the universe with hedonium. I don't want to be cuckolded by someone else's pretty network-TV values. I don't want to do anything I don't want to do, and I think that's what (bad) EAs, mother Teresa, and proselytizing Christians all get wrong. Doing things because they sound nice and pretty and someone else says they're morally good suuucks. Who even decided that warm fuzzies, QALYs, or shrimp lives saved are even good axes to optimize? Because surely everyone doesn't arrive at that conclusion independently. Optimizing such universally acceptable, bland metrics makes me feel like one of those blobby, soulless corporate automata in bad tech advertisements. I don't see why people obsess over the idea of universal ethics and doing the prosocial thing. There's no such thing as the Universal Best Thing, and professing the high virtue of maximizing happiness smacks of an over-RLHFed chatbot. Altruism might be a "virtue", as in most people's evolved and social environments cause them to value it, but it doesn't have to be. The cosmos doesn't care what values you have. Which totally frees you from the weight of "moral imperatives" and social pressures to do the right thing. There comes a time in most conscientious, top-of-distribution kids' lives when they decide to Save the World. This is very bad. Unless they really do get a deep, intrinsic satisfaction from maximizing expected global happiness, they'll be in for a world of pain later on. After years of spinning their wheels, not getting anywhere, they'll realize that they hate the whole principle they've built their life around. That, deep down, their truest passion doesn't (and doesn't have to) involve the number of people suffering malaria, the quantity of sentient shrimps being factory farmed, or how many trillion people could be happy in a way they aren't 1000 years from now. I claim that scope insensitivity isn't a bug. That there are no bugs when it comes to values. That you should care about exactly what you want to care about. That if you want to team up and save the world from AI or poverty or mortality, you can, but you don't have to. You have the freedom to care about whatever you want and shouldn't feel social guilt for not liking the same values everyone else does. Their values are just as meaningful (or meaningless) as yours. Peer pressure is an evolved strategy to elicit collaboration in goofy mesa-optimizers like humans, not an indication of some true higher virtue. Life is complex, and I really doubt that what you should care about can be boiled down to something so simple as quality-adjusted life-years. I doubt it can be boiled down at all. You should care about whatever you care about, and that probably won't fit any neat moral templates an online forum hands you. It'll probably be complex, confused, and logically inconsistent, and I don't think that's a bad thing Why do I care about this so much? Because I got stuck in exactly this trap at the ripe old age of 12, and it fucked me up good. I decided I'd save the world, because a lot of very smart people on a very cool site said that I should. That it would make me feel good and be good. That it mattered. The result? Years of guilt, unproductivity, and apathy. Ending up a moral zombie that didn't know how to care and couldn't feel emotion. Wondering why enlightenment felt like hell. If some guy promised to send you to secular heaven if you just let him fuck your wife, you'd tell him to hit the road. But people jump straight into the arms of this moral cuckoldry. Choosing and caring about your values is a very deep part of human nature and identity, and you shouldn't let someone else do it for you. This advice proba...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Saving the world sucks, published by Defective Altruism on January 10, 2024 on LessWrong. I don't want to save the world. I don't want to tile the universe with hedonium. I don't want to be cuckolded by someone else's pretty network-TV values. I don't want to do anything I don't want to do, and I think that's what (bad) EAs, mother Teresa, and proselytizing Christians all get wrong. Doing things because they sound nice and pretty and someone else says they're morally good suuucks. Who even decided that warm fuzzies, QALYs, or shrimp lives saved are even good axes to optimize? Because surely everyone doesn't arrive at that conclusion independently. Optimizing such universally acceptable, bland metrics makes me feel like one of those blobby, soulless corporate automata in bad tech advertisements. I don't see why people obsess over the idea of universal ethics and doing the prosocial thing. There's no such thing as the Universal Best Thing, and professing the high virtue of maximizing happiness smacks of an over-RLHFed chatbot. Altruism might be a "virtue", as in most people's evolved and social environments cause them to value it, but it doesn't have to be. The cosmos doesn't care what values you have. Which totally frees you from the weight of "moral imperatives" and social pressures to do the right thing. There comes a time in most conscientious, top-of-distribution kids' lives when they decide to Save the World. This is very bad. Unless they really do get a deep, intrinsic satisfaction from maximizing expected global happiness, they'll be in for a world of pain later on. After years of spinning their wheels, not getting anywhere, they'll realize that they hate the whole principle they've built their life around. That, deep down, their truest passion doesn't (and doesn't have to) involve the number of people suffering malaria, the quantity of sentient shrimps being factory farmed, or how many trillion people could be happy in a way they aren't 1000 years from now. I claim that scope insensitivity isn't a bug. That there are no bugs when it comes to values. That you should care about exactly what you want to care about. That if you want to team up and save the world from AI or poverty or mortality, you can, but you don't have to. You have the freedom to care about whatever you want and shouldn't feel social guilt for not liking the same values everyone else does. Their values are just as meaningful (or meaningless) as yours. Peer pressure is an evolved strategy to elicit collaboration in goofy mesa-optimizers like humans, not an indication of some true higher virtue. Life is complex, and I really doubt that what you should care about can be boiled down to something so simple as quality-adjusted life-years. I doubt it can be boiled down at all. You should care about whatever you care about, and that probably won't fit any neat moral templates an online forum hands you. It'll probably be complex, confused, and logically inconsistent, and I don't think that's a bad thing Why do I care about this so much? Because I got stuck in exactly this trap at the ripe old age of 12, and it fucked me up good. I decided I'd save the world, because a lot of very smart people on a very cool site said that I should. That it would make me feel good and be good. That it mattered. The result? Years of guilt, unproductivity, and apathy. Ending up a moral zombie that didn't know how to care and couldn't feel emotion. Wondering why enlightenment felt like hell. If some guy promised to send you to secular heaven if you just let him fuck your wife, you'd tell him to hit the road. But people jump straight into the arms of this moral cuckoldry. Choosing and caring about your values is a very deep part of human nature and identity, and you shouldn't let someone else do it for you. This advice proba...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: It is called Effective Altruism, not Altruistic Effectiveness, published by Timon Renzelmann on December 21, 2023 on The Effective Altruism Forum. This post is a personal reflection on certain attitudes I have encountered in the EA community that I believe can be misleading. It is primarily based on intuition, not thorough research and surveys. It is not news that the EA community has an unbalanced demographic, with men in the majority. I have heard from several women what they dislike about the EA community and this post is what I have taken from those conversations. I think that if we can move more in the direction I'm describing, the EA community can become warmer and more welcoming to all genders and races (and also more effective at doing good). I'd like to note that I don't think what I'm about to describe is a widespread problem, but a phenomenon that may occur in some places. Most of my experiences with the EA community have been very positive. I meet mostly caring people with whom I can have interesting, sometimes controversial discussions. And I often meet people who are very willing to help. Now to the subject: Some women I have spoken to have described a "lack of empathy" in the group, or, more specifically, that EA people came across as "tech bros" who lacked humility and wouldn't help a stranger because it wouldn't be the most effective thing to do. In an introductory discussion group we ran (in our university group), one of the participants perceived some of EA's ideas as "cold-hearted" and was very critical of the abstract, sometimes detached way of trying to calculate how to do good most effectively. I believe that these impressions and experiences point to risks associated with certain EA-related ideas. The idea of optimization Firstly, the idea of optimising/maximising one's impact is fraught with risks, which have been described already here, here and here (and maybe elsewhere, too). To judge between actions or causes as more or less worthy of our attention can certainly seem cold-hearted. While this approach is valuable for triage and for prioritising in difficult situations, it also has a dark side when it justifies not caring about what we might normally care about. We should not discredit what might be judged as lesser goods just because some metric suggests it. It shouldn't lead us to lose our humility (impacts are uncertain and we are not omniscient) as well as our sense of caring. What kind of community are we if people don't feel comfortable talking about their private lives because they don't optimise everything, don't spend their free time researching or trying to make a difference? When people think that spending time volunteering for less effective non-profits might not be valued or even dismissed? What is the point of an ineffective soup kitchen, after all it is a waste of time in terms of improving QALYs? I have no doubt that even the thought of encountering such insensitive comments makes you feel uncomfortable. The following quote might appear to conflict with the goal of EA, but I think it doesn't and makes and important point. "There is no hierarchy of compassionate action. Based on our interests, skills and what truly moves us, we each find our own way, helping to alleviate suffering in whatever way we can." - Joseph Goldstein (2007) in A Heart Full of Peace What we are trying to do is called Effective Altruism, not Altruistic Effectiveness, and we should be trying to be altruistic in the first place, that is, good and caring people.[1] The idea of focusing on consequences I also think that an exaggerated focus on consequences can be misleading in a social context, as well as detrimental in terms of personal well-being. Even if one supports consequentialism, focusing on consequences may not be the best strategy for achieving the...

Good Day and welcome to IAQ Radio+ episode 715 this week we welcome Dr. Gigi Kwik Gronvall, and Dr. Richard Bruns to discuss the recently developed Model State Indoor Air Quality Act. Gigi Kwik Gronvall, PhD During the COVID-19 pandemic, she led the Center's ongoing efforts to track the development and marketing of molecular and antigen tests and serology tests, as well as the development of national strategies for COVID-19 serology (antibody) tests and SARS-CoV-2 serosurveys in the United States. She leads work on improving indoor air quality to reduce pathogen transmission, including guidance for K-12 schools, and is a public health advisor to the Baltimore City Public School system. She also has written about the scientific response to the COVID-19 pandemic, the contested origin of SARS-CoV-2, and the implications for national and international security. Dr. Gronvall is the author of Synthetic Biology: Safety, Security, and Promise. In the book, she describes what can be done to minimize technical and social risks and maximize the benefits of synthetic biology, focusing on biosecurity, biosafety, ethics, and US national competitiveness—important sectors of national security. Dr. Gronvall is also the author of Preparing for Bioterrorism: The Alfred P. Sloan Foundation's Leadership in Biosecurity. Through her description of major grants that represented the foundation's investments in civilian preparedness, public health law, law enforcement, air filtering in buildings, influenza preparedness, and business preparedness, she constructed, for a nontechnical audience, a chronicle of early gains in US efforts to confront the threat of bioterrorism. Dr. Gronvall is a member of the Department of State's International Security Advisory Board, which provides advice about arms control, disarmament, nonproliferation, and national security aspects of emerging technologies. She is a member of the Novel and Exceptional Technology and Research Advisory Committee (NExTRAC), which provides recommendations to the Director of the National Institutes of Health and is a public forum for the discussion of the scientific, safety, and ethical issues associated with emerging biotechnologies. As of 2023, she is a member of the National Academies' Forum on Microbial Threats. From 2010 to 2020, Dr. Gronvall was a member of the Threat Reduction Advisory Committee, which provided the Secretary of Defense with independent advice and recommendations on reducing the risk to the United States, its military forces, and its allies and partners posed by nuclear, biological, chemical, and conventional threats. During 2014-2015, she led a preparatory group that examined the US government response to the Ebola outbreak in West Africa as a case study for the Department of Defense's strategic role in health security and made recommendations for future Department of Defense actions in response to disease outbreaks. She served as the Science Advisor for the Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism from April 2009 until the Commission ended in February 2010. She has testified before Congress about the safety and security of high-containment biological laboratories in the United States and served on several task forces related to laboratory and pathogen security. Dr. Gronvall has investigated and presented policy recommendations on the governance of science to the Biological Weapons Convention in Geneva, Switzerland. In addition to being a life member of the Council on Foreign Relations, Dr. Gronvall is an Associate Editor of the journal Health Security (formerly Biosecurity and Bioterrorism). She is a founding member of the Center. Prior to joining the faculty, she worked at the Johns Hopkins University Center for Civilian Biodefense Strategies. She was a National Research Council Postdoctoral Associate at the US Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland. Dr. Gronvall received a PhD from Johns Hopkins University for work on T-cell receptor/MHC I interactions and worked as a protein chemist at the Memorial Sloan-Kettering Cancer Center. She received a BS in biology from Indiana University, Bloomington. Richard Bruns, PhD PhD Clemson University 2012 MS Clemson University 2009 BS Western Carolina University 2004 Particular research interests are using cost-benefit analysis to make the world's preparations for pandemics and emerging biological risks as effective as possible; and expanding the use of QALYs to better measure a variety of life states and social conditions, so that cost-benefit analysis can include and properly account for all expected side effects of public policies. Previously, Richard was a Senior Economist at the Food and Drug Administration, doing cost-benefit modeling of many FDA regulations and actions, including the Intentional Adulteration rule designed to harden food production facilities against terrorist attacks, the PHO GRAS determination aka ‘trans fat ban', and a variety of other rules relating to food and medical devices. Richard also did preliminary modeling on FDA's upcoming Nicotine Product Standard, a de facto ban on cigarettes that would cause many significant effects on public health and safety, as well as research to quantify and monetize the marginal per-unit effects of a variety of food contaminants, such as mycological toxins and arsenic in rice.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: 1/E(X) is not E(1/X), published by EdoArad on November 9, 2023 on The Effective Altruism Forum. When modeling with uncertainty we often care about the expected value of our result. In CEAs, in particular, we often try to estimate E[effectcost]. This is different from both E[costeffect]1 and E[effect]E[cost] (which are also different from each other). [1] The goal of this post is to make this clear. One way to simplify this is to assume that the cost is constant. So we only have uncertainty about the effect. We will also assume at first that the effect can only be one of two values, say either 1 QALY or 10 QALYs with equal probability. Expected Value is defined as the weighted average of all possible values, where the weights are the probabilities associated with these values. In math notation, for a random variable X, where x are all of the possible values of X.[2] For non-discrete distributions, like a normal distribution, we'll change the sum with an integral. Coming back to the example above, we seek the expected value of effect over cost. As the cost is constant, say C dollars, we only have two possible values: In this case we do have E[effectcost]=E[effect]E[cost], but as we'll soon see that's only because the cost is constant. What about E[costeffect]? which is not 1E[effectcost]=C211$QALY, a smaller amount. The point is that generally 1E[X]E[1X]. In fact, we always have 1E[X]E[1X] with equality if and only if X is constant.[3] Another common and useful example is when X is lognormally distributed with parameters μ,σ2. That means, by definition, that lnX is normally distributed with expected value and variance μ,σ2 respectively. The expected value of X itself is a slightly more complicated expression: Now the fun part: 1X is also lognormally distributed! That's because ln1X=lnX. Its parameters are μ,σ2 (why?) and so we get In fact, we see that the ratio between these values is ^ See Probability distributions of Cost-Effectiveness can be misleading for relevant discussion. There are arguably reasons to care about the two alternatives E[costeffect]1 or E[effect]E[cost] rather than E[effectcost], which are left for a future post. ^ One way to imagine this is that if we sample X many times we will observe each possible value x roughly P(X=x) of the times. So the expected value would indeed generally be approximately the average value of many independent samples. ^ Due to Jensen's Inequality. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: About 'subjective' wellbeing and cost-effectiveness analysis in mental health, published by LondonGal on July 30, 2023 on The Effective Altruism Forum. Hello everyone, I was first 'sucked in' to this forum when I was directed to a post I might find interesting - it was about a research organisation with EA endorsement that was straying into my area of work, mental health. I'm a UK doctor specialising in psychiatry, with some research experience. To be honest, I was baffled and a little frustrated by how far this organisation strayed from what I would expect from mental health research - hence the (perhaps overly) technical diatribe I launched into on a website I hadn't visited before, about an organisation I hadn't heard of prior. However, that's not usually my style, and once I took a step back from my knee-jerk reaction, I wanted to understand how people with the same goals could arrive at completely different conclusions. It's led me to do a lot of reading, and I wanted to see if I could try on a makeshift 'EA' hat, with most of my philosophy knowledge gained from The Good Place, no economics experience, and see where it went. What I wanted to understand: Where has the interest in 'wellbeing' arisen from, and what does it mean? What are 'subjective wellbeing' (SWB) measures, and are they useful? Are we at a point of putting monetary value on SWB (e.g. like QALYs) for the sake of cost-effectiveness analysis (CEA)? When people are in this space talking about mental health, are we talking the same language? Why are RCTs the 'best' evidence for subjective wellbeing? What would I come up with from my perspective of working within mental health for a way of comparing different interventions based on their intended effects on wellbeing? a. Spillover effects b. Catastrophic multipliers How does my guess stack up against existing research into wellbeing? How could my framework be helpful in practice? What would I be suggesting as research areas for maximal gains in wellbeing from my biased perspective? I'm aware this might be well-trodden ground in EA, which would make me embarrassingly late to the party, and consequently a complete bore. To lay my cards firmly on the table, I did approach these questions from the perspective that mental health is desperately underfunded, I spend a lot of time with patients who are severely affected by mental illness and therefore I'm biased towards seeing 'wellbeing' as an opportunity to rebalance this scale and acknowledge the impact mental illnesses have on people. I also feel the term 'mental health' is used in a way which is often confusing and occasionally unhelpful or stigmatising. This is not meant as an attempt to further an argument against any person or organisation; it will also not be high in tech-speak as this was the first lesson I learnt very quickly on my journey - while jargon is a useful shorthand for talking with people in the same field, as an outsider it is exhausting. This post does not reflect the attitudes or opinions of anyone but me - this is my personal quest for common ground and understanding, not a representation of 'UK psychiatry' - I'm speaking in an entirely personal capacity and, accordingly, I'm assuming I've gotten a lot of it completely wrong. To make this less self-indulgent, I've arranged this post to follow that question-and-answer format. For the sake of transparency, this was how this work came to be: I started with a long piece of writing about my concerns with assumptions made about mental health interventions in low- or middle-income country (LMIC) settings. I then did a quick Google on the WELLBY and wrote a lot about the idea of asking people to rate their 'satisfaction with life' on a scale from 0-10 which was essentially just entirely critical. I subsequently wrote out my concept of wellbei...

Bill Smith of the Pioneer Institute in Massachusetts joins Wayne and Tim to discuss his important new book “Rationing Medicine”, which focuses on an obscure economic concept called QALYs – or quality adjusted life years.  Government bureaucrats in Europe use QALYs to deny access to life saving medications for patients.  Some in the U.S. are pushing for the adoption of QALYs as a way to address high prescription drug costs.  Learn how QALYs would jeopardize health care innovation and harm patients.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Relative Value Functions: A Flexible New Format for Value Estimation, published by Ozzie Gooen on May 18, 2023 on The Effective Altruism Forum. Summary Quantifying value in a meaningful way is one of the most important yet challenging tasks for improving decision-making. Traditional approaches rely on standardized value units, but these falter when options differ widely or lack an obvious shared metric. We propose an alternative called relative value functions that uses programming functions to value relationships rather than absolute quantities. This method captures detailed information about correlations and uncertainties that standardized value units miss. More specifically, we put forward value ratio formats of univariate and multivariate forms. Relative value functions ultimately shine where single value units struggle: valuing diverse items in situations with high uncertainty. Their flexibility and elegance suit them well to collective estimation and forecasting. This makes them particularly well-suited to ambitious, large-scale valuation, like estimating large utility functions. While promising, relative value functions also pose challenges. They require specialized knowledge to develop and understand, and will require new forms of software infrastructure. Visualization techniques are needed to make their insights accessible, and training resources must be created to build modeling expertise. Writing programmatic relative value functions can be much easier than one might expect, given the right tools. We show some examples using Squiggle, a programming language for estimation. We at QURI are currently building software to make relative value estimation usable, and we expect to share some of this shortly. We of course also very much encourage others to try other setups as well. Ultimately, if we aim to eventually generate estimates of things like: The total value of all effective altruist projects; The value of 100,000 potential personal and organizational interventions; or The value of each political bill under consideration in the United States; then the use of relative value assessments may be crucial. Presentation & Demo I gave a recent presentation on relative values, as part of a longer presentation in our work at QURI. This features a short walk-through of an experimental app we're working on to express these values. The Relative Values part of the presentation is is from 22:25 to 35:59. This post gives a much more thorough description of this work than the presentation does, but the example in the presentation might make the rest of this make more sense. Challenges with Estimating Value with Standard Units The standard way to measure the value of items is to come up with standardized units and measure the items in terms of these units. Many health measure benefits are estimated in QALYs or DALYs Consumer benefit has been measured in willingness to pay Longtermist interventions have occasionally been measured in “Basis Points”, Microdooms and Microtopias Risky activities can be measured in Micromorts COVID activities have been measured in MicroCOVIDs Let's call these sorts of units “value units” as they are meant as approximations or proxies of value. Most of these (QALYs, Basis Points, Micromorts) can more formally be called summary measures, but we'll stick to the term unit for simplicity. These sorts of units can be very useful, but they're still infrequently used. QALYs and DALYS don't have many trusted and aggregated tables. Often there are specific estimates made in specific research papers, but there aren't many long aggregated tables for public use. There are very few tables of personal intervention value estimates, like the net benefit of life choices. Very few business decisions are made with reference to clear units of value. For example, “Whi...

The Quality Adjusted Life Year, or QALY, was invented at the UK's University of York by Prof Alan Williams in the 1970s. Some currently engaged in the bitter trench warfare of America's drug pricing debate think it's high time for another British invasion, and the US should fully embrace the UK's use of QALYs. In this Vital Health Podcast, we have a discussion with William Smith, a Senior Fellow at the Pioneer Institute, about his recently published book, “Rationing Medicine: Threats from European Cost-Effectiveness Models to America's Seniors and other Vulnerable Populations.” William makes a strong case that the use of QALY for cost-effectiveness assessments within Medicare and Medicaid would violate several key provisions of the Americans with Disabilities Act.See omnystudio.com/listener for privacy information.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: A flaw in a simple version of worldview diversification, published by NunoSempere on May 15, 2023 on The Effective Altruism Forum. Summary I consider a simple version of “worldview diversification”: allocating a set amount of money per cause area per year. I explain in probably too much detail how that setup leads to inconsistent relative values from year to year and from cause area to cause area. This implies that there might be Pareto improvements, i.e., moves that you could make that will result in strictly better outcomes. However, identifying those Pareto improvements wouldn't be trivial, and would probably require more investment into estimation and cross-area comparison capabilities.1 More elaborate versions of worldview diversification are probably able to fix this particular flaw, for example by instituting trading between the different worldview—thought that trading does ultimately have to happen. However, I view those solutions as hacks, and I suspect that the problem I outline in this post is indicative of deeper problems with the overall approach of worldview diversification. The main flaw: inconsistent relative values This section perhaps has too much detail to arrive at a fairly intuitive point. I thought this was worth doing because I find the point that there is a possible Pareto improvement on the table a powerful argument, and I didn't want to hand-wave it. But the reader might want to skip to the next sections after getting the gist. Deducing bounds for relative values from revealed preferences Suppose that you order the ex-ante values of grants in different cause areas. The areas could be global health and development, animal welfare, speculative long-termism, etc. Their values could be given in QALYs (quality-adjusted life-years), sentience-adjusted QALYs, expected reduction in existential risk, but also in some relative unit2. For simplicity, let us just pick the case where there are two cause areas: More undilluted shades represent more valuable grants (e.g., larger reductions per dollar: of human suffering, animal suffering or existential risk), and lighter shades represent less valuable grants. Due to diminishing marginal returns, I've drawn the most valuable grants as smaller, though this doesn't particularly matter. Now, we can augment the picture by also considering the marginal grants which didn't get funded. In particular, imagine that the marginal grant which didn't get funded for cause #1 has the same size as the marginal grant that did get funded for cause #2 (this doesn't affect the thrust of the argument, it just makes it more apparent): Now, from this, we can deduce some bounds on relative values: In words rather than in shades of colour, this would be: Spending L1 dollars at cost-effectiveness A greens/$ is better than spending L1 dollars at cost-effectiveness B reds/$ Spending L2 dollars at cost-effectiveness X reds/$ is better than spending L2 dollars at cost-effectiveness Y greens/$ Or, dividing by L1 and L2, A greens is better than B reds X reds is better than Y reds In colors, this would correspond to all four squares having the same size: Giving some values, this could be: 10 greens is better than 2 reds 3 reds is better than 5 greens From this we could deduce that 6 reds > 10 greens > 2 reds, or that one green is worth between 0.2 and 0.6 reds. But now there comes a new year But the above was for one year. Now comes another year, with its own set of grants. But we are keeping the amount we allocate to each area constant. It's been a less promising year for green, and a more promising year for red, . So this means that some of the stuff that wasn't funded last year for green is funded now, and some of the stuff that was funded last year for red isn't funded now: Now we can do the same comparisons as the last time: And when ...

A new book from Dr. Bill Smith of the Pioneer Institute outlines how quality-adjusted life-years (QALYs) discriminate against patients and threaten rare disease innovation; Antonio Ciaccia breaks down Ohio's lawsuit against PBMs and the issue of vertical integration; and Pat Carroll from Connecticut talks about how copay accumulator programs make it difficult for patients to afford care. Crapo, Wyden Release Legislative Framework to Address PBMs, Prescription Drug Supply Chain Yost Sues Express Scripts, Prime Therapeutics and 5 Others, Blaming Exorbitant Drug Prices on Their Collusion Rationing Medicine: Threats from European Cost-Effectiveness Models to America's Seniors and other Vulnerable Populations Patients Rising Stories

A movement founded at the University of Oxford in 2009 has now captured the imagination – and the wallets – of some of the brightest and most successful across elite Western academic and business circles. Effective altruism, a 21st-century data-driven take on the philosophy of utilitarianism, claims we must give our time and money only to those causes which can be proven to increase the greatest amount of pleasure to the most people. Why has this eccentric community grown so fast, has it become unmoored from its original intentions, and what perverse incentives arise when we try to distil ethics into an algorithm? This Economist article asking if effective altruism has lost its way is well worth a read: https://www.economist.com/1843/2022/11/15/the-good-delusion-has-effective-altruism-broken-bad Subscribe to the Matters of Life and Death podcast: https://pod.link/1509923173 If you want to go deeper into some of the topics we discuss, visit John's website: http://www.johnwyatt.com For more resources to help you explore faith and the big questions, visit: http://www.premierunbelievable.com

This is the Weight and Healthcare newsletter! If you like what you are reading, please consider subscribing and/or sharing!In part 1 we talked about a request that has been submitted for the World Health Organization (WHO) to add diet drugs (specifically GLP1 agonists like Novo Nordisk's Saxenda and Wegovy) to their list of “essential medicines.” We discussed who was making this request and the justification that they were using. In part 2 we took a deeper dive into the research that they used to try to support this request, and in this final installment, we will look at the research around efficacy, harm, and cost-effectiveness.First I'll offer a summary for each issue and then I'll give a breakdowns of the research that they cite.  Just a quick reminder that this request is asking the World Health Organization (WHO) to add these drugs to their list of “essential medications” globally.Before we get into the sections, I want to mention two overarching issues that are found throughout the entirety of this request and the studies that are used to support it.First, in general, a belief has been fomented (predominantly by those in the weight loss industry) that being higher-weight is so terrible then it's worth “throwing anything at the problem.” This leads to acceptance of poor, short-term, and/or incomplete data as “good enough” to foist recommendations onto higher-weight people, which means that part of weight stigma in healthcare is that higher-weight people are afforded less right to ethical, evidence-based medicine than thinner people.Second, is clinging to correlation (without any mechanism of causation) when it comes to weight, health, and health outcomes, including the abject failure to consider confounding variables. So throughout these studies “being higher-weight is associated with [health issue(s)]” stated uncritically in support of weight loss interventions. There is an utter failure to explore the idea that the reason for the outcome differences is not weight itself but, instead, exposure to weight stigma, weight cycling (which these medications actually perpetuate by their own admission,) and healthcare inequalities.  Issues with research supporting effectiveness, harms, and benefitsStudy Duration:This is the main issue. While there was one study that went up to 106 weeks, the vast majority of the studies are between 14 and 56 weeks. We know that these drugs can have significant, even life-threatening side effects (earning them the FDA's strongest warning.) 14-56 weeks is not not nearly enough time to capture the danger of long-term effects, or to capture long-term trends around weight loss/weight regain.Study PopulationMany of the studies included have small samples. Many have study populations are overwhelmingly white, which is a huge issue when making a global recommendations.Small effect and overlapMany of the studies show only a bit of weight loss (often 15lbs or less) and often there was overlap in weight lost between the treatment group and the placebo group. Even using the “ob*sity” construct that this request is based on, for many people, this amount of weight loss wouldn't even change their “class” of “ob*sity.”Failure to capture adverse eventsMuch of the research they use to support their claims of safety didn't actually capture individual adverse events or serious adverse events. Often they only captured subjects who reported leaving treatment due to side effects.Issues with research supporting cost effectivenessThe cost-effectiveness analyses they cite are based on Quality Adjusted Life Years (QALYs). This is a measurement of the effectiveness of a medical intervention to lengthen and/or improve patients' lives.The calculation for this is [Years of Life * Utility Value = #QALY]So if a treatment gives someone 3 extra years of life with a Health-Related Quality of Life (HRQL) score of 0.7, then the treatment is said to generate 2.1 [3 x 0.7] QALYs.This is a complicated and problematic concept that deserves its own post sometime in the future, but looking just at this request I think it's important to note that they are working on two main unproven assumptions:1. That being higher weight causes lower health-related quality of life and/or shorter life span (rather than any lower HRQL being related to experiences that higher-weight people have including weight stigma, weight cycling, healthcare inequalities et al.) 2. That this treatment induces weight loss and/or health benefits that increase the life span and/or health-related quality of life of those who take it.I don't believe either of these assumptions are proven by the material cited in the request to the WHO. Specifically, it's very possible that it's not living in a higher-weight body, but rather the experiences that higher-weight people are more likely to have (weight stigma, weight cycling, healthcare inequalities) that impact their HRQL.Further, the short-term efficacy data available (and Novo Nordisk's own admission about high rates of regain) fall far short of proving any assumptions about these drugs ability to actually improve or extend life. Further, the failure of the literature to adequately capture negative side effects of the drugs, both short and long-term, means that this calculation cannot be properly made.Incremental Cost-Effectiveness Ratio (ICER)ICER is how QALYs are turned into a monetary value. It is calculated by dividing the difference in total costs by the difference in the chosen measure of health outcome or effect.[(Cost of intervention A -Cost of Intervention B) / (Effectiveness of Intervention A – Effectiveness of Intervention B)]The result is a ratio of extra cost per extra unit of health effect of a more vs less expensive treatment which can then be measured in QALYs.Again, this is worthy of its own post because there are all kinds of ethical issues around things like how we value life, how we define “healthy” and the ethics of determining whether or not prolonging someone's life is “cost effective.” I'm not going to do a deep dive into that today, but I do want to note that it is a serious issue in these kinds of calculations.In this specific case, even if one was to get past the ethical issues, an accurate calculation is impossible to make on both of the measures of the equation.Cost of these drugs varies wildly between countries and sometimes within countries because, for example, Novo Nordisk is a for-profit corporation whose goal is to create as much profit as possible.  Per the WHO request letter, the monthly cost of liraglutide is $126 in Norway and $709 in the US. Semaglutide is $95 per 30 days in Turkey, but $804 per 30 days in US.When it comes to effectiveness of the treatment, again, there is virtually no long-term data. We do know that in Novo Nordisk's own studies, weight is regained rapidly and cardiometabolic benefits are lost when the drugs are discontinued and even when people stay on the drugs, weight loss levels off after about a year, at 68 weeks weight cycling begins, and at 104 weeks (when follow-up ended) weight was trending up. It's possible that these drugs are utterly ineffective over the long-term and/or that the prevalence of long-term side effects renders any treatment effects moot. We simply do not know.I do not think that this is a remotely appropriate basis from which to request that these drugs be declared globally essential by the WHO.Here are the citation breakdowns. These are not deep dives since there are enough issues with the research on a simple surface analysis.Breakdowns of evidence of comparative effectivenessEffects of liraglutide in the treatment of ob*sity: a randomised, double-blind, placebo-controlled study, Astrup et al.)This is a 20-week study funded by Novo Nordisk. It included 564 people on various doses of liraglutide and a placebo group who didn't get the drug and a group on orlistat. There were no more than 90-98 people in each group.The study explains “Participants on liraglutide lost significantly more weight than did those on placebo” by which they meant that those on the highest dose of liraglutide lose about 9.7lbs more than those on the placebo over the 20 weeks.III LEAD studiesThese are four studies that look at liraglutide in combination with other drugs for the treatment of Type 2 Diabetes that also included some information on weight changes. One was 52 weeks, the others were  26, the maximum amount of weight lost was only about 5lbs.   The first [Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU), Marre et al] was a study that looked at the efficacy of adding liraglutide or rosiglitazone 4 to glimiperide in subjects with Type 2 Diabetes to test effects on blood sugar and body size.The study followed 1041 adults for 26 weeks. The study found that those on .6mg of liraglutide gained 0.7kg, those on 1.2mg gained 0.3kg, and those on 1.8mg of liraglutide lost 0.2kg, while those on placebo lost 0.1kg.The second [Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care, 2009. 32(1): p. 84-90. Nauck, M., et al.,]looked at the efficacy of adding liraglutide to metformin therapy for those with Type 2 Diabetes. They found that over the 26-week study those on liraglutide lost 1.8 ± 0.2, 2.6 ± 0.2, and 2.8 ± 0.2 kg for 0.6, 1.2, and 1.8 mg doses. Those on placebo lost 1.5 ± 0.3kg.The third [Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet, 2009. 373(9662): p. 473-81. Garber, A., et al.,] This was a study of the comparative effectiveness of Liraglutide versus glimepiride for type 2 diabetes, with small weight loss as an ancillary finding. Those in the liraglutide group lost an average of 2kg.The final study [Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD), Zinman et al.]  was a 26-week study with 533 total subjects. The goal was to study the efficacy of liraglutide when added to metformin and rosiglitazone for people with type 2 diabetes. They found that those on liraglutide lost between 0.7 and 2.3kg (1.5lbs to 5.1lbs) in 26 weeks.Meta-Analyses and Systematic Review FindingsEfficacy of Liraglutide in Non-Diabetic Ob*se Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Barboza, J.J., et al., None of the included studies were more than 56 weeks and one was only 14 weeks. One had as many as 3731 subjects, but one had only 40. Some had body weight loss as a primary outcome, but some did not. Maximum doses ranged from 1.8 to 3.0mg. The mean body weight reduction was  3.35 kg (7.4lbs) but in one study there was no difference in weight loss. The maximum difference was 6.3kg (13.9lbs)They also refer to Iqbal et al which we discussed in part 2.Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. Vilsbøll, T., et al.The included studies are between 20 and 53 weeks long, and include some of the studies they already cited individually above. Of the 25 included studies only 3 had “ob*sity” as the main inclusion criteria, the rest were Type 2 Diabetes.The mean weight loss for those on the highest dose of the drug was between 0.2kg and 7.2kg. For those in the control group it was 2.9 kg, so there was actually overlap between the treatment and placebo groups.Summary of evidence of safety and harmsThey begin with the claim “The safety profile of GLP-1 receptor agonists is also well studied”To support this they cite: Efficacy and Safety of Liraglutide 3.0 mg in Patients with Overweight and Ob*se with or without Diabetes: A Systematic Review and Meta-Analysis, Konwar, M., et al.,This included 14 total studies, many of which the authors of the WHO request had cited individually and were included in other systematic reviews and meta-analyses above. The smallest study included 19 people, the largest included 2,487. The total number of subjects was 4,142.Their conclusion was “Liraglutide in 3.0 mg subcutaneous dose demonstrated significant weight reduction with a reasonable safety profile for patients with overweight or ob*sity regardless of diabetic status compared to placebo.”Their methodology says that they omitted studies from analysis due to “short duration.” They included studies that had a minimum of 12 weeks and a maximum of 56 weeks of follow-up.While they included 14 studies, only 11 of them actually included information about adverse events.In terms of adverse effects (AEs,) they found that the pooled estimate of nine studies in nondiabetic patients and two studies in diabetic patients revealed a significant proportion of patients experiencing the adverse events in liraglutide 3.0 mg group when compared with placebo., and the pooled estimate of the eleven studies showed that liraglutide 3.0 mg had higher risk of AEs compared to placebo.When it came to “serious adverse events” they found that there was a similar risk level between the drug and placebo groups, but remember that's for only 12 to 56 weeks, and Novo Nordisk is recommending that people take these drugs for the rest of their lives. A few months to a little over a year is not enough time to capture long-term serious adverse events.The efficacy and safety of liraglutide in the ob*se, non-diabetic individuals: a systematic review and meta-analysis. Zhang, P., et al.,This included five RCTs (which were included in various of the above systemic reviews and meta-analyses) ranging in follow-up from 14 to 56 weeks.The only adverse event information captured was the number of people who withdrew from treatment due to adverse events (which they found was similar between drug and placebo) and nausea (which was experienced more by people on the drug.)So, in addition to being short in duration, this was far from a comprehensive list of side effects. They made no attempt to capture serious adverse side effects and their short-term nature would have made this difficult anyway.Association of Pharmacological Treatments for Ob*sity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. Khera, R., et al.This looked at weight loss and adverse events with a number of different weight loss drugs. Interestingly liraglutide did not show the highest amount of weight loss but was associated with the highest odds of adverse event–related treatment discontinuation. It should also be noted that high drop-out rates of 30-45% plagued all of the trials which the study authors admit means that “studies were considered to be at high risk of bias.“Given that those who drafted the WHO request are asking that these drugs be considered essential globally, it is disappointing that they included this study and didn't bother to mention this issue in their written request.This included 28 RCTs (most of which were included in other citations above) and only 3 that included liraglutide. They didn't capture individual adverse events, but only “Discontinuation of Therapy Due to Adverse Events.” They only evaluated a year of data so, again, while it is likely that these studies would have captured common adverse events had they bothered to try, there isn't long enough follow-up to have any information about serious (possibly life-threatening) long-term adverse events.Association of Glucagon-like Peptide 1 Analogs and Agonists Administered for Ob*sity with Weight Loss and Adverse Events: A Systematic Review and Network Meta-analysis. Vosoughi, K., et al.,This study included 64 RCTs with durations from 12 to 160 weeks, with a median of 26 weeks. As is common in these studies, the majority of the sample (74.9%) was white.Like those above, they only looked at treatment discontinuation from adverse events, they did not capture specific adverse events (common or serious.) Of the seven GLP-1 drugs they tested, liraglutide was tied with taspoglutide for the highest discontinuation of treatment due to adverse events.The study authors also note that “Risk of bias was high or unclear for random sequence generation (29.7%), allocation concealment (26.6%), and incomplete outcome data (26.6%).”Breakdowns for Comparative Cost-effectiveness StudiesFirst, the WHO request authors themselves admit that when it comes to cost-effectiveness, “the analyses have generally been performed only for high-income countries.” This is significant since they are asking the WHO to consider these drugs essential for the entire world.It's also important to understand that none of the data looks at a comparison of cost effectiveness for weight-neutral health interventions to these drugs. Without that information there is no way to calculate actual “cost effectiveness” since it's possible that weight-neutral health interventions would have greater benefits with less risk and dramatically lower cost.  NICE's guidance:  Liraglutide for managing overweight and ob*sity Technology appraisal guidance [TA664]Published: 09 December 2020.Do recall that NICE is involved in the current scandal with Novo Nordisk for influence peddling.These guidelines are created based on a submission of evidence by Novo Nordisk. The committee's understanding of “clinical need” was based on the testimony of a single “patient expert” who “explained that living with ob*sity is challenging and restrictive. There is stigma associated with being ob*se.”Once again we see a rush to blame body size for any “challenges” and “restrictions” of living in a higher-weight body, accompanied by the immediate decision that those bodies should be subjected to healthcare interventions that risk their lives and quality of life in order to be made (temporarily, by Novo and NICE's own admission) thinner.  There did not seem to be a patient expert to discuss the weight-neutral options.It was not immediately apparent if the patient expert was provided/paid by Novo Nordisk, but they certainly forwarded their narrative that simply living in a higher-weight body is a disease requiring treatment.It should be noted that while the trial Novo Nordisk submitted covered a wider range of people, they specifically submitted for this recommendation only the subgroup of that population who were diagnosed with “ob*sity,”  pre-diabetes, and a “high risk of cardiovascular disease based on risk factors such as hypertension and dyslipidaemia.”So, even if we accept this guidance as true, the WHO Essential Medicines request applies to a population much wider than this and so this fails to justify the cost-effectiveness for that population.This guidance is also based on the costs associated with obtaining the drugs through a “specialist weight management service” since an agreement is in place for Novo Nordisk to give a discount to these services.In calculating the ICER per QALY gained, the recommendations note that “Because of the uncertainties in the modelling assumptions, particularly what happens after stopping liraglutide and the calculation of long-term benefits, the committee agreed that an acceptable ICER would not be higher than £20,000 per QALY gained”Again, this recommendation is based on a trial submitted by Novo Nordisk that included 3,721 people and lasted for three years, but only 800 met the criteria for this cost-effectiveness recommendation. The trial failed to show a significant reduction in cardiovascular events. Novo's calculation of risk reduction was based on surrogate outcomes, which NICE points out “introduces uncertainty because causal inference requires direct evidence that liraglutide reduces cardiovascular events. This was not provided in the company submission because of lack of long-term evidence.”The NICE committee admits “relying on surrogates is uncertain but accepted that surrogate outcomes were the only available evidence to estimate cardiovascular benefits.”I just want to point out that another option would be to refuse to experiment on higher-weight people without appropriate evidence.These cost-effectiveness calculations are based on someone using the drug for two years, with no actual data on reduction in cardiovascular events, and with the admitted assumption that “any weight loss returned to the base weight 3 years after treatment discontinuation.” Said another way, this committee decided that it was cost effective to spend up to £20,000 per QALY for people to take a weight loss drug with significant side effects for two years, with no direct evidence of reduced cardiovascular events, and with the acknowledgment that people will be gaining all of their weight back when they stop taking it.Those who wrote the request for WHO to consider these drugs “essential” chose to characterize this as “At the chosen threshold of £20,000 per quality-adjusted life year (QALY) gained, the report concluded that liraglutide is cost-effective for the management of ob*sity.” I do not think that is an accurate characterization of the findings.The request cites “A report by the Canadian Agency for Drugs and Technologies in Health (CADTH) found that compared to standard care, the ICER for liraglutide was $196,876 per QALY gained”For the US, they cite a study that found that to achieve ICERs between $100,000 and $150,000 perQALY or evLY gained, the health-benefit price benchmark range for semaglutide was estimated as $7500 - $9800 per year, which would require a discount of 28-45% from the current US net price.They also cite “Cost-effectiveness analysis of semaglutide 2.4 mg for the treatment of adult patients with overweight and ob*sity in the United States, Kim et al.Let's take a look at their conflict of interest disclosure (emphasis mine)“Financial support for this research was provided by Novo Nordisk Inc. The study sponsor [that means Novo Nordisk] was involved in several aspects of the research, including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication.Dr Kim and Ms Ramasamy are employees of Novo Nordisk Inc. Ms Kumar and Dr Burudpakdee were employees of Novo Nordisk Inc at the time this study was conducted. Dr Sullivan received research support from Novo Nordisk Inc for this study. Drs Wang, Song, Wu, Ms Xie, and Ms Sun are employees of Analysis Group, Inc, who received consultancy fees from Novo Nordisk Inc in connection with this study.”Given that, you probably won't be shocked to learn that this concluded that Novo Nordisk's drug, semaglutide, was cost-effective. The reason I bolded the text above is that this study is based on modeling – they are taking what is, by their own admission, a “new drug” and making predictions for 30 years. Everything was simulated based on trial data (you know, those trials that we've been discussing that often have horrendous methodology…) and “other relevant literature.” The construction of the modeling and the interpretation of the results was directed by the company who stands to benefit financially from the findings, and carried out by that company's employees and consultants.  Also, and I'll just quote again here since I don't think I can improve on their text “Cost-effectiveness was examined with a willingness-to-pay (WTP) threshold of $150,000 per QALY gained” I do not think that this WTP is based on a global assessment.In their (and by their I mean Novo Nordisk's) modeling they find that semaglutide was estimated to improve QALYs by 0.138 to 0.925 and incur higher costs by $3,254 to $25,086 over the 30-year time horizon vs comparators.And, again, this is without any kind of actual long-term data. I think that the best way to characterize this information is “back of the envelope calculations” at best.To sum up, I do not think that the research they cite comes anywhere close to proving that these drugs have levels of efficacy, safety, or cost-effectiveness that warrant their addition to the WHO list of essential medicines. I believe that if the WHO grants this request I think it will be an affront to medical science, it will cheapen the concept of “essential medicines,” and it will harm untold numbers of higher-weight people all over the world.Did you find this post helpful? You can subscribe for free to get future posts delivered direct to your inbox, or choose a paid subscription to support the newsletter and get special benefits! Click the Subscribe button below for details:Liked this piece? Share this piece:More research and resources:https://haeshealthsheets.com/resources/*Note on language: I use “fat” as a neutral descriptor as used by the fat activist community, I use “ob*se” and “overw*ight” to acknowledge that these are terms that were created to medicalize and pathologize fat bodies, with roots in racism and specifically anti-Blackness. Please read Sabrina Strings' Fearing the Black Body – the Racial Origins of Fat Phobia and Da'Shaun Harrison's Belly of the Beast: The Politics of Anti-Fatness as Anti-Blackness for more on this. Get full access to Weight and Healthcare at weightandhealthcare.substack.com/subscribe

This week, Jeremy is joined by Sara Van Geertruyden, executive director of the Partnership to Improve Patient Care, to talk about legislation moving through Congress that would extend prohibitions on the use of quality adjusted life years (QALYs) in drug pricing and access decisions.Read the National Council on Disabilities report finding QUALYs to be discriminatory at https://ncd.gov/sites/default/files/NCD_Quality_Adjusted_Life_Report_508.pdf This episode is brought to you by The ALS Association in partnership with CitizenRacecar.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Saving drowning children in light of perilous maximisation, published by calebp on April 2, 2023 on The Effective Altruism Forum. Last year Holden Karnofsky wrote the post, “EA is about maximization, and maximization is perilous”. You could read the post, but I suggest you just jump on board because Holden is cool, and morality is hard. Given that you now believe that maximisation of doing good is actually bad and scary, you should also probably make some adjustments to the classic thought experiment you use to get your friends on board with the new mission of “do the most good possible [a large but not too large amount of good] using evidence and reason”. A slightly modified drowning child thought experiment goes as follows Imagine that you are walking by a small pond, and you see five children drowning. You can easily save the child without putting yourself in great danger, but doing so will ruin your expensive shoes. Should you save the children? Obviously, your first instinct is to save all the children. But remember, maximisation is perilous. It's this kind of attitude that leads to atrocities like large financial crimes. Instead, you should just save three or four of the children. That is still a large amount of good, and importantly, it is not maximally large. But what should you do if you encounter just one drowning child? The options at first pass seem bleak – you can either: Ignore the child and let them drown (which many people believe is bad). Save the child (but know that you have tried to maximise good in that situation). I think there are a few neat solutions to get around these moral conundrums: Save the child with some reasonable probability (say 80%). Before wading into the shallow pond, whip out the D10 you were carrying in your backpack. If you roll an eight or lower, then go ahead and save the child. Otherwise, go about your day. Only partially save the child You may have an opportunity to help the child to various degrees. Rather than picking up the child and then ensuring that they find their parents or doing other previously thought as reasonable things, you could: Move the child to shallower waters so they are only drowning a little bit. Help the child out of the water but then abandon them somewhere within a 300m radius of the pond. Create a manifold market on whether the child will be saved and bid against it to incentivise other people to help the child. The QALY approach Save the child but replace them with an adult who is not able to swim (but is likely to have fewer years of healthy life left). Commit now to a policy of only saving children who are sufficiently old or likely to have only moderately healthy/happy lives. The King Solomon approach Cut the child in half and save the left half of them from drowning Using these approaches, you should be able to convey the optimal most Holden-approved amount of good. If you like, you can remember the heuristic “maximisation bad”. As well as other things like eradicating diseases. QALYs are quality-adjusted life years (essentially a metric for healthy years lived). Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: It's "The EA-Adjacent Forum" now, published by Lizka on April 1, 2023 on The Effective Altruism Forum. TL;DR: We're not really comfortable calling ourselves “EAs.” Moreover, we know that this is true for a lot of people in the EA community the eclectic group of people trying to make the world better who happen to use the Forum. So we're renaming the “Effective Altruism Forum” to be the "EA-Adjacent Forum" (“EA Forum” for short). We have some deep disagreements with EA Look, we run a forum focused on discussions about how to do the most good we can, and we work at the "Centre for Effective Altruism," but we're not really members of the EA community. We have some deep disagreements with many parts of the movement. (We don't even always agree with each other about our disagreements, we don't always think that the EA thing is the right thing (see also), and we even hosted an EA criticism contest to surface disagreements.) It's not just us We know that others who use the Forum also prefer to call themselves “EA-adjacent.” We're also somewhat worried that anything that someone posts on the EA Forum can be interpreted as representative of effective altruism. We think it's important to preserve nuance and be clear about the facts listed here, so we're rebranding. Impact of the rebrand, next steps It's already the case that “EA” often stands for “Ea-Adjacent,” and we don't think the rebrand will change much in terms of how the Forum will function. As always, we'd love to hear your feedback. You can comment here or contact us directly. (Thanks to [unnamed people] for suggesting this rebrand. We'd credit them directly, but some of them prefer to not associate so closely with EA.) The EA-Adjacent Forum team. Please note that not all teammates agree with everything written here (probably). Some example disagreements: 1) We disagree with a lot of people in the EA community about styling and font choices. 2) Most people in the EA community promote functional decision theory, but after spending many years making software for the forum, we've come to the conclusion that object-oriented decision theory is superior.3) We disagree with CEA about the spelling of “Centre” in “Centre for Effective Altruism.” It should be spelled “center” as Noah Webster intended.4) Many EAs appear to focus on scope sensitivity, but we think scope specificity is more neglected5) We think QALYs should be converted to their metric-system equivalent, such that 1 metric QALY is the amount of quality-adjusted life that can be supported by 1 joule of energy within a 1-cubic-meter box over 1 year at 0 degrees celsius. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.

For more than 40 years, the quality-adjusted life year (QALY) has been devaluing the lives of older adults and patients with chronic medical conditions. Yet, thanks to organizations like Patients Rising, we may finally put these discriminatory assessments to rest once and for all. In light of the recent QALY Ban Bill introduced to Congress, we're joined by returning guest, Co-Founder, and CEO of Patients Rising, Terry Wilcox, to break down the impact of QALYs on patients whose quality of life relies on access to critical treatments.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Shallow Investigation: Stillbirths, published by Joseph Pusey on March 13, 2023 on The Effective Altruism Forum. This topic has the potential to be deeply upsetting to those reading it, particularly to those who have personal experience of the topic in question. If you feel that I've missed or misunderstood something, or could have phrased things more sensitively, please reach out to me. Throughout the review, words like “woman” or “mother” are used in places where some people might prefer “birthing person” or similar. This choice reflects the language used in the available literature and does not constitute a position on what the most appropriate terminology is. This report is a shallow dive into stillbirths, a sub-area within maternal and neonatal health, and was produced as part of the Cause Innovation Bootcamp. The report, which reflects approximately 40-50 hours of research, offers a brief dive into whether a particular problem area is a promising area for either funders or founders to be working in. Being a shallow report, it should be used to decide whether or not more research and work into a particular problem area should be prioritised. Executive Summary Importance: This problem is likely very important (epistemic status-strong)- stillbirths are widespread, concentrated in the world's poorest countries, and decreasing only very slowly compared to the decline in maternal and infant mortality. There are more deaths resulting from stillbirth than those caused by HIV and malaria combined (depending on your personal definition of death- see below), and even in high-income countries stillbirths outnumber infant deaths. Tractability: This problem is likely moderately tractable (moderate)- most stillbirths are likely to be preventable, but the most impactful interventions are complex, facility-based, expensive, and most effective at scale e.g. guaranteeing access to high-quality emergency obstetric care Neglectedness: This problem is unlikely to be neglected (less strong)- although still under-researched and under-counted, stillbirths are the target of some of the largest organisations in the global health and development world, including the WHO, UNICEF, the Bill and Melinda Gates Foundation, and the Lancet. Many countries have committed to the Every Newborn Action Plan, which aims- amongst other things- to reduce the frequency of stillbirths. Key uncertainties Key uncertainty 1: Accurately assessing the impact of stillbirths, and therefore the cost-effectiveness of interventions aimed at reducing stillbirths, depends significantly on to what extent direct costs to the unborn child are counted. Some organisations view stillbirths as having negative effects on the parents and wider communities but do not count the potential years of life lost by the unborn child; others use time-discounting methods to calculate a hypothetical number of expected QALYS lost, and still others see it as completely equivalent to losing an averagely-long life. Differences in the weighting of this loss can alter the calculated impacts of stillbirth by several orders of magnitude and is likely the most important consideration when considering a stillbirth-reducing intervention Key uncertainty 2: Interventions which reduce the risk of stillbirth tend to be those which also address maternal and neonatal health more broadly; therefore, it is very difficult to accurately assess the cost-effectiveness of these interventions solely in terms of their impact on stillbirths, and more complex models which take into account the impacts on maternal, neonatal, and infant health are likely more accurate in assessing the overall cost-effectiveness of interventions. Key uncertainty 3: A large proportion of the data around interventions to reduce stillbirths comes from high-income countries, but most still...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Bill prohibiting the use of QALYs in US healthcare decisions?, published by gordoni on March 12, 2023 on The Effective Altruism Forum. Is anyone familiar with H.R. 485? It has been introduced in the House, but it is not yet law. According to the CRS "This bill prohibits all federal health care programs, including the Federal Employees Health Benefits Program, and federally funded state health care programs (e.g., Medicaid) from using prices that are based on quality-adjusted life years (i.e., measures that discount the value of a life based on disability) to determine relevant thresholds for coverage, reimbursements, or incentive programs". I think the motivation might be to prevent discrimination against people with disabilities, but it seems to me like it goes too far. It seems to me it would prevent the use of QALYs for making decisions such as is a particular cure for blindness worthwhile, and how might it compare to treatments for other diseases and conditions. Is anyone familiar with this bill and able to shed more light on it? Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.

Quality-adjusted life years — or QALYs — is a tool designed to help measure the cost effectiveness of drugs and other medical treatments. But detractors say the statistic discriminates against people with disabilities by undervaluing how much treatments help them. Ben Leonard talks with host Carmen Paun about the debate over the use of the statistic.

Ahead of Rare Disease Day, Congresswoman Cathy McMorris Rodgers (WA-05) joins the podcast to discuss new legislation that would ban the use of a discriminatory health care metric, quality adjusted life year, or QALY. Learn how the QALY hurts treatment access for patients with rare diseases and disabilities, and how a government ban on QALYs would create more equitable access to care. Plus, hear from Jean Baker, who shares her challenges getting coverage for her husband's rare form of cancer, anaplastic thyroid cancer. And our patient correspondents from the rare disease community talk about the health care issues that impact them. This is also our last Friday episode of the Patients Rising Podcast! You'll be able to catch the Patients Rising Podcast on Mondays, starting March 6th, in a brand new format. Hosts: Terry Wilcox, CEO, Patients RisingDr. Robert Goldberg, “Dr. Bob,” Co-Founder and Vice President of the Center for Medicine in the Public InterestGuests:Congresswoman Cathy McMorris Rodgers, Chair, House Energy and Commerce CommitteeJean Baker, Rare Disease Caregiver and Anaplastic Thyroid Cancer AdvocateMaggie Senese, Patient CorrespondentKaitlyn Trevathan, Patient CorrespondentTomisa Starr, Patient CorrespondentAvery Roberts and Kelly Berger, Patient CorrespondentLinks: Chairs Rodgers, Smith, and Reps. Burgess, Wenstrup Introduce Legislation to Ban QALYsContact your Representative and Urge Them to Ban the QALYRare Disease Day February 28, 2023 Health Technology Assessment Best Practices for Rare Disease DrugsNeed help?The successful patient is one who can get what they need when they need it. We all know insurance slows us down, so why not take matters into your own hands? Our Navigator is an online tool that allows you to search a massive network of health-related resources using your zip code so you get local results. Get proactive and become a more successful patient right now at PatientsRisingConcierge.orgHave a question or comment about the show, or want to suggest a show topic or share your story as a patient correspondent?Drop us a line: podcast@patientsrising.orgThe views and opinions expressed herein are those of the guest(s)/ author(s) and do not reflect the official policy or position of Patients Rising, nor do the views and opinions stated on this show reflect the opinions of a guest's current or previous employers.

Via new guidance and its Project Optimus, FDA is pushing companies to do dose-optimization studies instead of maximum-tolerated dose studies, BioCentury Executive Director Lauren Martz said on the latest BioCentury This Week podcast. Martz and colleagues discuss the burdens and benefits of the shift, in particular for biotechs. BioCentury's editors also assess new challenges and opportunities for FDA and regulated industry now that the agency is starting to implement PDUFA VII and mandates from the spending bill passed by Congress late last year, including clinical trials diversity, and analyze a move in the House of Representatives to ban the use by federal or state governments of quality-adjusted life years (QALYs) to make health coverage or pricing decisions.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: What I thought about child marriage as a cause area, and how I've changed my mind, published by Catherine Fist on January 31, 2023 on The Effective Altruism Forum. Summary: I have been working on a research project into the scale, tractability and neglectedness of child marriage. After 80 hours of research, I thought that there was a relatively strong case that effective altruist funding organisations that fund projects addressing international poverty should consider funding child marriage interventions. I then found a source that undermined a key premise: child marriage is clearly harmful across a number of health metrics. I describe in more detail my experience and findings below, and share some tips for those undertaking self-directed research projects to avoid making the mistakes I made (skip to ‘What I will do next time' for these). Context: I had no direct experience researching child marriage, but I was interested to learn about effective interventions and whether it had potential as a possible cause area. I studied Political Science and International Relations at University, as well as some subjects on development, gender and economics, I have also worked as a government evaluator. My goal was to do some preliminary research and determine if child marriage was large scale problem, tractable and neglected. If so, I would share this research with effective altruist funders. My model: In October last year, I started a self-directed research project into the scale, tractability and neglectedness of child marriage. I read and collected dozens of sources, analyzed data, contacted a top researcher, compared effective interventions, built a mental model of what the charitable space looked like and identified potential interventions for EA support. I came to the following findings, based on around 80 hours of research: Scale/importance Child marriage is a widespread practice that affects around 12 millions girls per year (UNICEF, 2022) Child marriage is a harmful practice that increases the risk of negative maternal and sexual health outcomes, domestic and sexual violence, and reduces the likelihood that a girl will complete school. This is the consensus position held by global development institutions (see meeting report from leading global institutions on child marriage UNFPA, 2019). Tractability There are cost effective interventions that work to prevent child marriage, e.g. the ‘cost per marriage averted' ranged between US$159 and US$732 in this study (Erulkar, Medhin and Weissman 2017). The effect of child marriage on quality adjusted or disability adjusted life years has not been quantified so it difficult to compare cost effectiveness with other interventions (EA Forum explainer on these metrics). Neglectedness Population Council is a research body focussed on running quasi-experimental programs and creating scalable interventions (Population Council, date unknown). The lead investigator into child marriage at Population Council informed me that it is not currently running programs to prevent child marriage because of lack of funding. Conclusion Effective altruist funding organisations focused on international health and poverty should consider funding effective interventions to prevent child marriage at a large scale. What broke my model Earlier this week, I decided it would be useful to try and quantify the harm of child marriage, or at least some of the harms, into commonly used metrics like quality adjusted or disability adjusted life years (QALYs or DALYs). I anticipated that this would be a key piece of information for EA funders, and it had not been done so far (finding 2b). In doing so, I came across a study that fundamentally challenged finding 1b: child marriage is an underlying cause of many harmful outcomes. Without strong evidence that child marri...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Replace Neglectedness, published by Indra Gesink on January 16, 2023 on The Effective Altruism Forum. for example with Leverage, as featured in Will MacAskill's What We Owe the Future. The second bullet point featured in the website introduction to effective altruism is the ITN framework. This exists to prioritize problems. The framework does so by considering the Importance — or scale, S — of a problem, as the number of people or quality-adjusted life years (QALYs) affected, multiplied with the Tractability, as the potential that this problem can be addressed, and Neglectedness, as the number of people already working to address this problem (ITN-framework, including Leverage). Tractibility is sometimes also called Solvability, and non-neglectedness crowdedness. Some criticisms and difficulties in interpreting the framework (1, 2, 3, 4) have preceded this forum post. The ITN framework can be interpreted - as also in the final paragraph of (1) - such that IT represents the potential that a problem can be addressed, while ITN considers the difference that any one individual can make to that problem, particularly the next individual. How much impact can the next individual make, choosing to work on this problem, on average? Why do I add “on average”? We are still ignoring the person's unique qualities, and instead more abstractly consider an average person. Adding “personal fit” as another multiplicative factor would make it personal as well. So “How much impact can the next individual make on this problem?” really asks for the marginal counterfactual impact. Respectively this is the amount of impact that this one individual adds to the total impact so far, which would not happen otherwise. The ITN-factor Neglectedness assumes that this marginal counterfactual impact is declining — strictly — as more individuals join the endeavor of addressing the particular problem. If this is true, then — indeed — a more neglected problem ceteris paribus — i.e. not varying factors I, T (or personal fit) simultaneously — always yields more impact when fewer individuals are already addressing it. This is however not always true, as also already pointed out in the criticisms referenced above. Consider the following string of examples. Suppose a partial civilizational collapse has occurred, and you consider whether it would be good to go and repopulate the now barren lands. The ITN-framework says that as the first person to do so you make the biggest difference. However, alone you cannot procreate, at least not without far-reaching technological assistance. In fact a sizable group of people deciding to do so might very well still be ineffective, by not bringing in sufficient genetic diversity. This is captured by a well-known term in population biology: the critical or minimally viable population size (to persist). Something similar operates to a lesser extent in the effectiveness of teams. I for example once found the advice to better not join a company as the sole data scientist, as you would not have a team to exchange ideas with. Working together, you become more effective, and develop more. Advocating for policies is another area that is important and where you need teams. Consider there being multiple equally worthwhile causes to protest for, but by the logic of the ITN-framework you always join the least populated protest. And no critical mass is obtained. Doesn't that seem absurd? See also (5). (And the third image in (3), depicting a one-time significant increase in marginal counterfactual impact, as with a critical vote to establish a majority. This graph is also called an indicator function). Effective altruists might similarly often find themselves advocating for policies which are neglected and that are thus not well known to the recipient of such advocacy. As opposed to max...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Do better, please ..., published by Rohit is a Strange Loop on January 15, 2023 on The Effective Altruism Forum. I am not a card carrying member of EA. I am not particularly A, much less E in that context. However the past few months have been exhausting in seeing not just the community, one I like, in turmoil repeatedly, while clearly fumbling basic aspects of how they're seen in the wider world. I like having EA in the world, I think it does a lot of good. And I think you guys are literally throwing it away based on aesthetics of misguided epistemic virtue signaling. But it's late, and I read more than a few articles, and this post is me begging you to please just stop. The specific push here is of course the Bostrom incident, when he clearly and highly legibly wrote black people have lower intelligence than other races. And his apology, was, to put it mildly, mealy mouthed and without much substance. If anything, in the intervening 25 years since the offending email, all he seems to have learnt to do is forget the one thing he said he wanted to do - to speak plainly. I'm not here to litigate race science. There's plenty of well reviewed science in the field that demonstrates that, varyingly, there are issues with measurements of both race and intelligence, much less how they evolve over time, catch up speeds, and a truly dizzying array of confounders. I can easily imagine if you're young and not particularly interested in this space you'd have a variety of views, what is silly is seeing someone who is so clearly in a position of authority, with a reputation for careful consideration and truth seeking, maintaining this kind of view. And not only is this just wrong, it's counterproductive. If EA wants to work on the most important problems in the world and make progress on them, it would be useful to have the world look upon you with trust. For anything more than turning money into malaria nets, you need people to trust you. And that includes trusting your intentions and your character. If you believe there are racial differences in intelligence, and your work forces you to work on the hard problems of resource allocation or longtermist societal evolution, nobody will trust you to do the right tradeoffs. History is filled with optimisation experiments gone horribly wrong when these beliefs existed at the bottom. The base rate of horrible outcomes is uncomfortably large. This is human values misalignment. Unless you have overwhelming evidence (or any real evidence), this is just a dumb prior to hold and publicise if you're working on actively changing people's lives. I don't care what you think about ethics about sentient digital life in the future if you can't figure this out today. Again, all of which individually is fine. I'm an advocate of people holding crazy opinions should they want to. But when like a third of the community seems to support him, and the defenses require contortions that agree, dismiss and generally be whiny about drama, that's ridiculous. While I appreciate posts like this, which speak about the importance of epistemic integrity, it seems to miss the fact that applauding someone for not lying is great but not if the belief they're holding is bad. And even if this blows over, it will remain a drag on EA unless it's addressed unequivocally. Or this type of comment which uses a lot of words but effectively seems to support the same thought. That no, our job is to differentiate QALYs and therefore differences are part of life. But guess what, epistemic integrity on something like this (I believe something pretty reprehensible and am not cowing to people telling me so) isn't going to help with shrimp welfare or AI risk prevention. Or even malaria net provision. Do not mistake "sticking with your beliefs" to be an overriding good, above believing w...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Carl Djerassi (1923–2014), published by Gavin on November 29, 2022 on The Effective Altruism Forum. Carl Djerassi helped invent the synthetic hormone norethindrone, one of the 500 most important medicines (actually top 50 by prescription count). A large supply is a basic requirement of every health system in the world. Norethindrone is important for two reasons. First, it treats menstrual disorders and endometriosis, together 0.3% of the global burden of disease. More famously, it was a component of The Pill. People mix up the timelines, which is why he is sometimes called the 'Father of the Pill'. But "neither Djerassi nor the company he works for, Syntex, had any interest in testing it as a contraceptive" and it was only used for birth control 12 years after. As usual in industrial chemistry, Djerassi got no royalties from the blockbuster medicine he helped develop - but, surprise ending! - he bought cheap shares in Syntex and got rich when it became one of the most important medicines in history for two reasons. He also synthesized the third-ever practical antihistamine, and applied new instruments in 1,200 papers on the structure of many important steroids. He also worked on one of the first AI programs to do useful work in science. Achievements Epistemic status: little better than a guess. Not many inventions are fully counterfactual; most simple, massively profitable things which get invented would have been invented by someone else a bit later. So the appropriate unit for lauding inventors is years saved. And if I put a number on that I'd just be making it up. Here are the numbers I made up: About 4 million US users, so maybe up to 94 million world users at present. No sense of the endometriosis / contraception split. Call it 600 million users, 10% endometriosis use case. For menstrual disorders: on the market 65 years and counting. Counterfactual: on the market 3 years before the next oral progestogen was. It was the first practical oral progestogen, so we should compare to the injectable alternatives About 1/6 of Americans hate needles so much that they refuse treatment. Attrition and missed doses for needle treatments is higher than pill treatments. Endometriosis is about 0.25 - 0.35 QALY loss. So if it's 30% effective, around $30 / QALY, an amazing deal. For easy contraception: on the market 59 years and counting. The big gains (besides autonomy) are averting unintended pregnancies, abortions, and pregnancy-related deaths. Modern cost-effectiveness in Ethiopia is $96 / QALY. There's probably some additive effect for endometriosis sufferers (who would want contraception anyway). A full account would guess the Pill's effect on the sexual revolution and cultural attitudes toward women. But I've reached my limit. (You might also consider the role of the Pill in the ongoing decline of church authority: "1980: In spite of the Pope's ruling against the Pill and birth control, almost 80% of American Catholic women use contraceptives, and only 29% of American priests believe it is intrinsically immoral.") How many years did he bring the invention forward? Call it 5. Then split the credit three ways with Luis Miramontes and George Rosenkranz. So (largely made-up numbers) it looks like millions of QALYs for the treatment overall, and tens of thousands counterfactually for Djerassi. Artist After surviving cancer, he decided to become a writer. I was very depressed, and for the first time thought about mortality. Strangely enough I had not thought about death before... I realized that who knows how long I would live? In cancer they always talk about five years: if one can survive five years then presumably the cancer had been extirpated. And I thought: gee, had I known five years earlier that I would come down with cancer, would I have led a different life during these...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: The elephant in the bednet: the importance of philosophy when choosing between extending and improving lives, published by MichaelPlant on November 18, 2022 on The Effective Altruism Forum. Michael Plant, Joel McGuire, and Samuel Dupret Summary How should we compare the value of extending lives to improving lives? Doing so requires us to make various philosophical assumptions, either implicitly or explicitly. But these choices are rarely acknowledged or discussed by decision-makers, all of them are controversial, and they have significant implications for how resources should be distributed. We set out two crucial philosophical issues: (A) an account of the badness of death, how to determine the relative value of deaths at different ages, and (B) locating the neutral point, the place on the wellbeing scale at which life is neither good nor bad for someone. We then illustrate how different choices for (A) and (B) alter the cost-effectiveness of three charities which operate in low-income countries, provide different interventions, and are considered to be some of the most cost-effective ways to help others: Against Malaria Foundation (insecticide-treated nets), GiveDirectly (cash transfers), and StrongMinds (group therapy for depression). We assess all three in terms of wellbeing-adjusted life years (WELLBYs) and explain why we do not, and cannot, use standard health metrics (QALYs and DALYs) for this purpose. We show how much cost-effectiveness changes by shifting from one extreme of (reasonable) opinion to the other. At one end, AMF is 1.3x better than StrongMinds. At the other, StrongMinds is 12x better than AMF. We do not advocate for any particular view. Our aim is simply to show that these philosophical choices are decision-relevant and merit further discussion. Our results are displayed in the chart below, which plots the cost-effectiveness of the three charities in WELLBYs/$1,000. StrongMinds and GiveDirectly are represented with flat, dashed lines because their cost-effectiveness does not change under the different assumptions. The changes in AMF's cost-effectiveness are a result of two varying factors. One is using different accounts of the badness of death, that is, ways to assign value to saving lives at different ages; these three accounts go by unintuitive names in the philosophical literature, so we've put a slogan in brackets after each one to clarify their differences: deprivationism (prioritise the youngest), the time-relative interest account (prioritise older children over infants), and Epicureanism (death isn't bad for anyone – prioritise living well, not living long). We also consider including two variants of the time-relative interest account (TRIA); on these, life has a maximum value at the ages of either 5 or 25. The other factor is where to locate the neutral point, the place at which someone has overall zero wellbeing, on a 0-10 life satisfaction scale; we assess that as being at each location between 0/10 and 5/10. As you can see, AMF's cost-effectiveness changes a lot. It is only more cost-effective than StrongMinds if you adopt deprivationism and place the neutral point below 1. 1. Introduction How should we compare the value of extending lives to improving lives? Let's focus our minds with a real choice. On current estimates, for around $4,500, you can expect to save one child's life by providing insecticide-treated nets (ITNs). Alternatively, that sum could provide a $1,000 cash transfer to four-and-a-half families living in extreme poverty ($1,000 is about a year's household income). The cost of both choices is the same, but the outcomes differ. Which one will do the most good? This is a difficult and discomforting ethical question. How might we answer it? And how much would different answers change the priorities? There are various m...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Speculation on Current Opportunities for Unusually High Impact in Global Health, published by johnswentworth on November 11, 2022 on LessWrong. Epistemic Status: armchair speculation from a non-expert. Short version: I expect things to get pretty bad in the Sahel region over the next year in particular. The area is an obvious target for global health interventions even in good times, and impact is presumably higher in bad times. A simple baseline intervention: fill a backpack with antibiotics, fly to the region, and travel around distributing the antibiotics. What's The “Sahel” Region? The Sahel is a semi-arid region along the southern edge of the Sahara desert. Think roughly Mali, Niger, Chad and Sudan. Bad How? Based on statistics on the Sahel, it's one of the few remaining regions on Earth where the population is near Malthusian equilibrium. Fertility is high, contraception is rare; about half the population is under age 16. Infant mortality is around 6-8%, and ~a quarter of children are underweight. (Source: CIA World Factbook entries on Mali, Niger, Chad and Sudan.) Being near Malthusian equilibrium means that, when there's an economic downturn, a substantial chunk of the population dies. Die How? Traditional wisdom says: war, famine, disease. In this case, I'd expect famine to be the main instigator. Empty bellies then induce both violence and weak immune systems. On priors, I'd expect infectious disease to be the main proximate killer. The Next Year In Particular? The global economy has been looking rough, between the war in Ukraine shocking oil and food markets, and continuing post-Covid stagflation. Based on pulling a number out of my ass without looking at any statistics, I'd guess deaths from violence, starvation, and disease in the Sahel region will each be up an order of magnitude this year/next year compared to a good year (e.g. the first-quartile best year in the past decade). That said, the intervention we'll talk about is probably decently impactful even in a good year. So What's To Be Done? Just off the top of my head, one obvious baseline plan is: Fill a hiking backpack with antibiotics (buy them somewhere cheap!) Fly to N'Djamena or take a ferry to Timbuktu Obtain a motorbike or boat Travel around giving away antibiotics until you run out Repeat Note that you could, of course, substitute something else for "antibiotics" - maybe vitamins or antifungals or water purification tablets or iron supplements or some mix of those is higher marginal value. There are some possibly-nonobvious considerations here. First, we can safely assume that governments in the area are thoroughly corrupt at every level, and presumably the same goes for non-government bureaucracies; trying to route through a local bureaucratic machine is a recipe for failure. Thus, the importance of being physically present and physically distributing things oneself. On the other hand, physical safety is an issue, even more so if local food insecurity induces local violence or civil war. (That said, lots of Westerners these days act like they'll be immediately assaulted the moment they step into a “bad neighborhood” at night. Remember, folks, the vast majority of the locals are friendly the vast majority of the time, especially if you're going around obviously helping people. You don't need to be completely terrified of foreign territory. But, like, don't be completely naive about it either.) Also, it is important to explain what antibiotics are for and how to use them, and there will probably be language barriers. Literacy in these regions tends to be below 50%, and presumably the rural regions which most need the antibiotics also have the lowest literacy rates. How Much Impact? I'm not going to go all the way to estimating QALYs/$ here, but. according to this source, the antibiotic impor...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Speculation on Current Opportunities for Unusually High Impact in Global Health, published by johnswentworth on November 11, 2022 on LessWrong. Epistemic Status: armchair speculation from a non-expert. Short version: I expect things to get pretty bad in the Sahel region over the next year in particular. The area is an obvious target for global health interventions even in good times, and impact is presumably higher in bad times. A simple baseline intervention: fill a backpack with antibiotics, fly to the region, and travel around distributing the antibiotics. What's The “Sahel” Region? The Sahel is a semi-arid region along the southern edge of the Sahara desert. Think roughly Mali, Niger, Chad and Sudan. Bad How? Based on statistics on the Sahel, it's one of the few remaining regions on Earth where the population is near Malthusian equilibrium. Fertility is high, contraception is rare; about half the population is under age 16. Infant mortality is around 6-8%, and ~a quarter of children are underweight. (Source: CIA World Factbook entries on Mali, Niger, Chad and Sudan.) Being near Malthusian equilibrium means that, when there's an economic downturn, a substantial chunk of the population dies. Die How? Traditional wisdom says: war, famine, disease. In this case, I'd expect famine to be the main instigator. Empty bellies then induce both violence and weak immune systems. On priors, I'd expect infectious disease to be the main proximate killer. The Next Year In Particular? The global economy has been looking rough, between the war in Ukraine shocking oil and food markets, and continuing post-Covid stagflation. Based on pulling a number out of my ass without looking at any statistics, I'd guess deaths from violence, starvation, and disease in the Sahel region will each be up an order of magnitude this year/next year compared to a good year (e.g. the first-quartile best year in the past decade). That said, the intervention we'll talk about is probably decently impactful even in a good year. So What's To Be Done? Just off the top of my head, one obvious baseline plan is: Fill a hiking backpack with antibiotics (buy them somewhere cheap!) Fly to N'Djamena or take a ferry to Timbuktu Obtain a motorbike or boat Travel around giving away antibiotics until you run out Repeat Note that you could, of course, substitute something else for "antibiotics" - maybe vitamins or antifungals or water purification tablets or iron supplements or some mix of those is higher marginal value. There are some possibly-nonobvious considerations here. First, we can safely assume that governments in the area are thoroughly corrupt at every level, and presumably the same goes for non-government bureaucracies; trying to route through a local bureaucratic machine is a recipe for failure. Thus, the importance of being physically present and physically distributing things oneself. On the other hand, physical safety is an issue, even more so if local food insecurity induces local violence or civil war. (That said, lots of Westerners these days act like they'll be immediately assaulted the moment they step into a “bad neighborhood” at night. Remember, folks, the vast majority of the locals are friendly the vast majority of the time, especially if you're going around obviously helping people. You don't need to be completely terrified of foreign territory. But, like, don't be completely naive about it either.) Also, it is important to explain what antibiotics are for and how to use them, and there will probably be language barriers. Literacy in these regions tends to be below 50%, and presumably the rural regions which most need the antibiotics also have the lowest literacy rates. How Much Impact? I'm not going to go all the way to estimating QALYs/$ here, but. according to this source, the antibiotic impor...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: $5k challenge to quantify the impact of 80,000 hours' top career paths, published by NunoSempere on September 23, 2022 on The Effective Altruism Forum. Motivation 80,000 hours has identified a number of promising career paths. They have a fair amount of analysis behind their recommendations, and in particular, they have a list of top ten priority paths. However, 80,000 hours doesn't quite have quantitative estimates of these paths' value. Although their usefulness would not be guaranteed, quantitative estimates could make it clearer: how valuable their top career paths are relative to each other how valuable their top career paths are relative to options further down their list at which level of personal fit one should switch between different career paths where the expected impact is coming from, and which variables we are most uncertain about eventually, whether certain opportunities are valuable in themselves or for the value of information or career capital that they provide etc. The Prize Following up on the $1,000 Squiggle Experimentation Challenge and the Forecasting Innovation Prize we are offering a prize of $5k for quantitative estimates of the value of 80,000 hours' top 10 career paths. Rules Step 1: Make a public post online between now and December 1, 2022. Posts on the EA Forum (link posts are fine) are encouraged.Step 2: Complete this submission form. Further details Participants can use units or strategies of their choice—these might be QALYs, percentage points of reduction in existential risk, basis points of the future, basis points of existential risk reduced, career-dependent units, etc. Contestants could also use some other method, like relative values, estimating proxies, or some original option. We are specifically looking for quantitative estimates that attempt to estimate some magnitude reasonably close to the real world, similar to the units above. So for example, assigning valuations from 0 to 5 stars would not fulfil the requirements of the contest, but estimates in terms of the units above would qualify. Participants are free to estimate the value of one, several, or all ten career paths. Participants are free to use whatever tool or language they want to produce these estimates. Some possible tooling might be: Excel, Squiggle, Guesstimate, probabilistic languages or libraries (e.g., Turing.jl, PyMC3, Stan), Causal, working directly in a popular programming language, etc. Participants can provide point estimates of impact, but they are encouraged to provide their estimates as distributions instead. Participants are free to estimate the impact of a marginal person, of a marginal person with a good fit, the average value, etc. Participants are welcome to provide both average and marginal value—for example, they could provide a function which provides an estimate of marginal value at different levels of labor and capital. We provide some examples of possible rough submissions in an appendix. We are also happy to comment on estimation strategies: feel free to leave a comment on this post or to send a message to Nuño Sempere using the EA forum message functionality. Judging The judges will be Nuño Sempere, Eli Lifland, Alex Lawsen and Sam Nolan. These judges will judge on their personal capacities, and their stances do not represent their organizations. Judges will estimate the quality and value of the entries, and we will distribute the prize amount of $5k in proportion to an equally weighted aggregate of those subjective estimates. To reduce our operational burden, we are looking to send out around three to five prizes. If there are more than five submissions, we plan to implement a lottery system. For example, a participant who would have won $100 would instead get a 10% chance of receiving $1k. Acknowledgements This contest is a project of...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: EA Culture and Causes: Less is More, published by Allen Bell on August 16, 2022 on The Effective Altruism Forum. Should there be a community around EA? Should EA aim to be one coherent movement? I believe in the basic EA values and think they are important values to strive for. However, I think that EA's current way of self-organizing – as a community and an umbrella for many causes – is not well suited to optimizing for these values. In this post I will argue that there are substantial costs to being a community (as opposed to being “just” a movement or a collection of organizations). Separately, I will argue that EA has naturally grown in scope for the past ten years (without much pruning), and that now may be a good time to restructure. In the following sections I will explore (potential) negative facets of EA as a community and as a large umbrella of causes: If the community aspect of EA becomes too dominant, then we will find ourselves with cult-like problems, such as: the incentive for people to stay in the community being stronger than the incentive to be truth-seeking. Currently, EA's goal is very broad: “do good better”. Originally, colloquially it meant something fairly specific: when considering where to donate, keep in mind that some (traditional) charities save much more QALYs per dollar than others. However, over the past ten years the objects of charity EA covers have vastly grown in scope e.g. animals and future beings (also see a and b). We should beware that we don't reach a point where EA is so broad (in values) that the main thing two EAs have in common is some kind of vibe: ‘we have similar intellectual aesthetics' and ‘we belong to the same group', rather than ‘we're actually aiming for the same things'. EA shouldn't be some giant fraternity with EA slogans as its mottos, but should be goal-oriented. I think most of these issues would go away if we: De-emphasize the community aspect Narrow the scope of EA, for example into: A movement focusing on doing traditional charities better; and an independent Incubator of neglected but important causes 1. Too Much Emphasis on Community In this section I will argue that a) EA is not good as a community and b) being a community is bad for EA. That is, there are high costs associated with self-organizing as a community. The arguments are independent, so the costs you associate with each argument should be added up to get a lower bound for the total cost of organizing as a community. Problems with Ideological Communities in General The EA-community is bad in the sense that any X-community is bad. EA in itself is good. Community in itself is good. However, fusing an idea to a community is often bad. Groups of people can lie anywhere on the spectrum of purpose vs people. On one extreme you have movements or organizations that have a purpose and people coordinating to make it happen. Think of a political movement with one narrow, urgent purpose. People in this movement form an alliance because they want the same outcome, but they don't have to personally like each other. On the other end of the extreme you have villages, in which people support each other but don't feel the urge to be on the same page as their neighbor ideologically. (They may find the guy who cares a lot about X a weirdo, but they accept him as one of them.) For an unexpected example, consider the Esperanto community. This community was founded on an idea, but today it is very much at the community end of the spectrum rather than the ideological one. Both extremes (main focus on ideology/purpose or on community/people) can be healthy. However, combining ideology with community tends to lead to dysfunctional dynamics. The ideology component takes a hit because people sacrifice epistemics and goal-directedness for harmony. At the same time, the ...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: To WELLBY or not to WELLBY? Measuring non-health, non-pecuniary benefits using subjective wellbeing, published by JoelMcGuire on August 11, 2022 on The Effective Altruism Forum. This essay was written for the Worldview Investigations category of Open Philanthropy's Cause Exploration Prizes by staff at the Happier Lives Institute Summary Open Philanthropy recognises the need to measure benefits beyond health and income. We think that subjective wellbeing is the best tool for the task. Subjective wellbeing (SWB) is measured by asking people to rate how they think or feel about their lives. We propose the wellbeing-adjusted life year (WELLBY), the SWB equivalent of the DALY or QALY, as the obvious framework to do cost-effectiveness analyses of non-health, non-pecuniary benefits. As our previous work has shown that using WELLBYs can change funding priorities by giving more weight to improving mental health, compared to DALYs or income measures; and they may reveal different priorities in other areas too. The advantages of SWB over alternatives are fourfold. (1) SWB captures and integrates the overall benefit to the individual from all of the instrumental goods provided by an intervention. This avoids the challenging problem of assigning moral weights to different goods, makes spillover effects easier to estimate, and clarifies the importance of philosophy. (2) SWB is based on self-reports by the affected individuals whereas Q/DALYs rely on flawed predictions about how good or bad we think a malady will be for ourselves or others. (3) Using SWB will reveal previously under-captured benefits, such as it has already done for psychotherapy. (4) Measures of subjective wellbeing already exist, are easy to collect, and widely (and increasingly) used in academia and policymaking across an extensive array of circumstances and populations of interest. Furthermore, subjective wellbeing measures are reliable and valid instruments and the existing evidence supports consistent use across people. Having said that, SWB is not without its disadvantages. (1) There is little research on the comparability between SWB scales across people. (2) We don't know where the ‘neutral point' lies on SWB scales. (3) We're unsure how to choose the best measure of SWB (e.g., life satisfaction or happiness) or how to convert between them. (4) There are very few cost-effectiveness analyses using WELLBYs. Fortunately, we think these issues can be resolved and we are actively working towards doing so. 1. The problem and a solution Open Philanthropy's mission is to help others as much as possible. Its human-focused Global Health and Wellbeing grantmaking aims to save lives, improve health, and increase incomes. However, Open Philanthropy recognises that measuring changes to health or income does not capture all the benefits experienced by the recipients. So, they ask, how should they account for the effects of injustice, discrimination, empowerment, and freedom? To that list, we could also add crime, loneliness, and corruption. Whilst the standardised health metrics, QALYs and DALYs, make it easier to compare different health states in the same units, the broader challenge is to find a common currency that allows sensible trade-offs between health, wealth, and non-health, non-wealth outcomes. How could this be done? We take it that Open Philanthropy is interested in funding interventions that improve wellbeing. Therefore, reducing discrimination (or injustice, etc.) is good mostly because it increases wellbeing, any other reason is secondary. But what is ‘wellbeing'? Philosophers have three main theories: (1) positive experiences, (2) satisfied desires, and (3) a multi-item ‘objective list' that includes ‘objective' goods such as knowledge, achievement, and love. Conspicuously absent from this list are wealt...

HEALTH NEWS   Cocoa flavanols may be able to reduce blood pressure Cool room temperature inhibited cancer growth in mice Smells experienced in nature evoke positive wellbeing Healthy lifestyle may buffer against stress-related cell aging, study says Zinc plus antioxidants: A cost-effective solution to macular degeneration? Passive exercise offers same brain health benefits as active movements, study finds Cocoa flavanols may be able to reduce blood pressure University of Surrey (UK), July 23, 2022 A recent study found that cocoa flavanols can effectively lower blood pressure in people with ideal blood pressure, but not when it was already low, as well as reduce arterial stiffness.  Researchers of the current study note that previous controlled clinical intervention studies have demonstrated the blood pressure-decreasing and arterial stiffness-reducing effects of cocoa flavanols (CF) in healthy humans. However, as these studies were in tightly controlled settings, the researchers wanted to see how well this intervention played out in real-life scenarios. The researchers used an n-of-1 study design, where a small number of participants were exposed to the same intervention or the placebo multiple times. They then compared the results for each individual as well as between individuals.  The study included eleven healthy adults who received alternating doses of cocoa flavanol capsules and placebo capsules for eight days.  The results showed that cocoa flavanols were effective in lowering blood pressure and reducing arterial stiffness.  One concern about using cocoa flavanols to lower blood pressure is the risk of the blood pressure dropping too low. However, in this study, researchers found that the cocoa had less impact when blood pressure was lower, indicating it was a potentially safe intervention.  Prof. Christian Heiss, study author and professor of cardiovascular medicine, explained to MNT:  “The study confirms that cocoa flavanols can lower blood pressure and improve arterial stiffness. The new thing is that it does so in the normal life of healthy people and only lowers it if it is ‘high' even in the ‘normal range.” Cool room temperature inhibited cancer growth in mice Karolinska Institutet, August 5, 2022 Turning down the thermostat seems to make it harder for cancer cells to grow, according to a study in mice by researchers at Karolinska Institutet in Sweden. The study, published in the journal Nature, found that chilly temperatures activate heat-producing brown fat that consumes the sugars the tumors need to thrive. Similar metabolic mechanisms were found in a cancer patient exposed to a lowered room temperature. "We found that cold-activated brown adipose tissue competes against tumors for glucose and can help inhibit tumor growth in mice," says Professor Yihai Cao at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and corresponding author. "Our findings suggest that cold exposure could be a promising novel approach to cancer therapy, although this needs to be validated in larger clinical studies." The study compared tumor growth and survival rates in mice with various types of cancer, including colorectal, breast and pancreatic cancers, when exposed to cold versus warm living conditions. Mice acclimatized to temperatures of 4 degrees Celsius had significantly slower tumor growth and lived nearly twice as long compared with mice in rooms of 30 degrees Celsius. They found that cold temperatures triggered significant glucose uptake in brown adipose tissue, also known as brown fat, a type of fat that is responsible for keep the body warm during cold conditions. At the same time, the glucose signals were barely detectable in the tumor cells. When the researchers removed either the brown fat or a protein crucial for its metabolism called UCP1, the beneficial effect of the cold exposure was essentially wiped out and the tumors grew at a pace on par with those that were exposed to higher temperatures. Similarly, feeding tumor-bearing mice with a high sugar drink also obliterated the effect of cold temperatures and restored tumor growth. "Interestingly, high sugar drinks seem to cancel out the effect of cold temperatureson cancer cells, suggesting that limiting glucose supply is probably one of the most important methods for tumor suppression," Yihai Cao says.   Smells experienced in nature evoke positive wellbeing University of Kent (UK), August 5, 2022 Smells experienced in nature can make us feel relaxed, joyful, and healthy, according to new research led by the University of Kent's Durrell Institute of Conservation and Ecology (DICE). Smells were found to play an important role in delivering well-being benefits from interacting with nature, often with a strong link to people's personal memories, and specific ecological characteristics and processes (e.g. fallen leaves rotting in the winter). Researchers found that smells affected multiple types of human well-being, with physical well-being noted most frequently, particularly in relation to relaxation, comfort and rejuvenation. Absence of smell was also perceived to improve physical well-being, providing a cleansing environment due to the removal of pollution and unwanted smells associated with urban areas, and therefore enabling relaxation. Relaxation reduces stress and lowers cortisol levels, which is often linked to a multitude of diseases, and so these findings could be particularly significant to public health professionals. The research, carried out in woodland settings across four seasons, also found that smells evoked memories related to childhood activities. Many participants created meaningful connections with particular smells, rather than the woodland itself, and associated this with a memorable event. This, in turn, appeared to influence well-being by provoking emotional reactions to the memory.   Healthy lifestyle may buffer against stress-related cell aging, study says University of California at San Francisco  July 29, 2022   A new study from UC San Francisco is the first to show that while the impact of life's stressors accumulate overtime and accelerate cellular aging, these negative effects may be reduced by maintaining a healthy diet, exercising and sleeping well.    "The study participants who exercised, slept well and ate well had less telomere shortening than the ones who didn't maintain healthy lifestyles, even when they had similar levels of stress," said lead author Eli Puterman, PhD, assistant professor in the department of psychiatry at UCSF. "It's very important that we promote healthy living, especially under circumstances of typical experiences of life stressors like death, caregiving and job loss."   In the study, researchers examined three healthy behaviors –physical activity, dietary intake and sleep quality – over the course of one year in 239 post-menopausal, non-smoking women. In women who engaged in lower levels of healthy behaviors, there was a significantly greater decline in telomere length in their immune cells for every major life stressor that occurred during the year. Yet women who maintained active lifestyles, healthy diets, and good quality sleep appeared protected when exposed to stress – accumulated life stressors did not appear to lead to greater shortening.    "This is the first study that supports the idea, at least observationally, that stressful events can accelerate immune cell aging in adults, even in the short period of one year. Exciting, though, is that these results further suggest that keeping active, and eating and sleeping well during periods of high stress are particularly important to attenuate the accelerated aging of our immune cells," said Puterman.  Zinc plus antioxidants: A cost-effective solution to macular degeneration? University of Washington and University College London, July 30, 2022 A formula supplement containing anti-oxidants plus zinc appears to be cost-effective in slowing the progression of the ‘wet' form of the most common degenerative eye disease, finds a new study in British Journal of Ophthalmology. The cost savings and effectiveness of the supplement in advanced (category 4) cases of neovascular (wet-form) Age Related Macular Degeneration (nAMD) are such that their use should be considered in public health policy, recommend the multi-centre study team on behalf of the UK Electronic Medical Record (EMR) AMD Research Team.  Category 4 individuals who already had nAMD in one eye, showed a cost saving of nearly €3250 (£3000) per patient over the lifetime of treatment, compared to those not given supplements. The Age Related Eye Disease Study (AREDS) formula supplements also increased quality-adjusted life years (QALYs) by 0.16. “AREDS supplements are a dominant cost-effective intervention for category 4 AREDS patients, as they are both less expensive than standard care and more effective, and therefore should be considered for public funding,” wrote lead researcher Dr. Adnan Tufail. The study examined the use of AREDS formulation 1 and formulation 2 supplements.  AREDS 1 contained 80milligrams (mg) zinc, 2 mg copper, 500 mg vitamin C, 15 mg beta-carotene, 400 IU vitamin E. AREDS 2 reduced the amount of zinc to 25 mg, excluded beta-carotene (due to potential higher cancer risk in smokers), and added 10 mg lutein, 2 mg zeaxanthin, 1000 mg omega-3 fatty acids (650 mg docosahexaenoic acid and 350 mg eicosapentaenoic acid). These findings are consistent with previous research demonstrating the effectiveness of AREDS supplementss. Consequently, the researchers advocate the use of supplements to reduce the necessity for ranibizumab injections, which is the standard NHS treatment for AMD.   Passive exercise offers same brain health benefits as active movements, study finds University of Western Ontario, August 4, 2022 A new study by kinesiology graduate students from Western has found passive exercise leads to increased cerebral blood flow and improved executive function, providing the same cognitive benefits as active exercise. Published in Psychophysiology, the study is the first to look at whether there would be benefits to brain health during passive exercise where a person's limbs are moved via an external force—in this case, cycle pedals pushed by a mechanically driven flywheel.  During a 20-minute session with healthy young adults, the team found an improvement in executive function of the same magnitude for both the passive and the active exercise conditions, without an increase in heart rate or diastolic blood pressure.  Executive function is a higher-order cognitive ability that allows people to make plans and supports the activities of daily living. People who have mild cognitive impairments, such as people experiencing symptoms of early-stage Alzheimer's, can find their executive function negatively affected.  Previous research has documented that active exercise, where a person activates their muscles of their own volition, can increase blood flow to the brain and improve executive function. Passive exercise also increases blood flow to the brain, but this is significantly less documented.   During passive exercise, a person's limbs move and their muscle receptors are being stretched. That information is sent to the brain, indicating that more blood is needed in the moving areas of the body and in connected regions of the brain. This increase in cerebral blood flow, while significantly less than with active exercise, produced executive function improvements of a similar magnitude—an exciting result for the researchers.  "The potential impact for people with limited or no mobility could be profound. If done regularly, the increase in blood flow to the brain and resultant improvement in executive function will, optimistically, become a compounding effect that has a significant impact on cognitive health and executive function," Heath explained. 

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Baby Cause Areas, Existential Risk, and Longtermism, published by Davidmanheim on May 25, 2022 on The Effective Altruism Forum. This is a considered personal view, and discusses my understanding of a consensus among many core members of the movement. Longtermism is a big new thing in effective altruism - so big, it seems to crowd out discussion of other topics. This can lead to understandable feelings of neglect and favoritism on the part of dedicated proponents of other priorities. It doesn't mean that other areas of effective altruism are less important1 or are being discarded, but as I recall from my childhood growing up with a younger brother, older siblings don't always appreciate the situation, even when they understand different people, and different cause areas, have different needs at different times. As almost everyone I'm aware of in effective altruism has made clear, there is tremendous value in improving global health and welfare, in reducing animal suffering, and in reducing extreme risks, all areas which effective altruism has long prioritized. And despite reasonable claims that each area deserves to be prioritized over the others, there are fundamental and unresolvable debates about the relative importance of different areas. Given that, moral and epistemic uncertainties should lead us to be modest about any conclusions. And according to at least some views about moral uncertainty, that means we should balance priorities across the cause areas which cannot be directly compared. Within each area of concern, of course, there are tremendous inequities and misallocation which Effective Altruism has only begun to address. Americans spend $60 billion per year on their pets, and at most, a few hundred million dollars on EA-oriented animal welfare. (In contrast to the $500 billion spent on animal agriculture!) Similarly, $10 trillion is spent on healthcare globally, but that overwhelmingly goes to rich countries spending on their citizenry, rather than increasing quality of life and buying QALYs in the poorest countries, focusing on the most vulnerable. There is a tremendous amount that can be done! But just like animal welfare is relatively neglected compared to spending on healthcare, existential risk reduction is neglected relative to both, and longtermist areas other than near-term existential risk are barely getting any funding at all, especially outside of EA circles. Neglectedness is one critical part of explaining what is happening - that is, because some areas are relatively neglected, there are far larger opportunities for impact. Existential risk reduction was, historically, the focus of far less spending than the other cause areas. In EA this was presumably due to less perceived and/or actual tractability, and globally was more likely due to the same poor prioritization we see elsewhere. But as people have made stronger arguments for both importance and for tractability, and have found clear ways to actually address the problems, they have become the focus of far more effort within EA. But because of these changes, organizations within EA are also less mature, and need more attention as an area to determine what is most effective. And that goes even more for longtermism. But these have not and will not displace other causes. Thankfully, we can keep putting money into GiveDirectly, Deworm the World, and various anti-malaria campaigns - and we have! And so have many, many non-EA donors - In 2021, GiveDirectly gave $10m/month, but USAID, the US government foreign aid program, has embraced the strategy, as had the UK's DFID. Not only have we started chipping away at the highest leverage paces to give, but neglectedness has been decreasing. Similarly, Effective Altruists have donated tens of millions to reduce the burden of malaria, but the world has s...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Impact is very complicated, published by Justis on May 22, 2022 on The Effective Altruism Forum. Epistemic status: gestural food for thought. This is a post to aggregate a bunch of boring or obvious observations that are easy to overlook. I don't expect anything to be new. But I do think difficulties gauging impact, in aggregate, form a sort of missing mood that we should be paying more attention to. At the end of the post, I'll touch on why. Let us count the ways Here are some factors that can make assessing impact complex: Some interventions are backed by scientific studies. Scientific studies vary in quality in many ways. They can be larger or smaller, more or less numerous, clearly biased or apparently unbiased, clearly significant or only marginally significant, randomized or non-randomized, observational or experimental, etc. Even for good studies, the same interventions may become better or worse over time as conditions in the world change, or may be very particular to certain places. Cash transfers, for example, might just work way better in certain parts of the world than others, and it may be hard to predict how or why in advance. Many interventions require many simultaneous layers of involvement. Suppose I give to the Against Malaria Foundation. I can say "I estimate I am saving a life per $5,000 I spend." But I read Peter Singer when I was 13, then Scott Alexander when I was 19, and I likely wouldn't have ended up donating much without these. I also couldn't give to AMF if it didn't exist, so I owe a debt to Rob Mather. And perhaps whoever told Scott Alexander about AMF. All these steps are necessary to actually "save a life", so we run the risk of massively overcounting if we give every person in the chain "full credit". But there's no objectively rigorous way to decide who gets how much of the credit! Just using counterfactuals doesn't work; it may be the case that all of us are required and a single person "out of the chain" breaks it down. But we can't all get all the credit! Plus many interventions, like in the AMF example, mostly are just reducing probabilities across large numbers of people anyway. What does it even mean for "my money" to "save life". Once the money all goes into a pool, whose money actually funds which nets anyway? And which nets prevent cases of malaria that would have been fatal? No way to answer these questions even in principle. Some (perhaps all) interventions rely on difficult-to-impossible philosophical questions to resolve. How should we weigh insect suffering? All we can do is guess - learning more facts about insects doesn't really get us over Nagel's "What is it like to be a bat?" hurdle. Empirical information, analogies, and intuition pumps all can help, but there are fundamental judgment calls at play. How to assess well being and weigh well being against survival is another example here where it's hard to boil down to numbers: there are lots of ways to do it (QALYs, seeing how much people would pay to avert various harms, natural experiments) but none is perfect and all involve their own judgment calls. Some interventions require certain thresholds being met or they don't actually accomplish anything. Donating to a political campaign that promises credibly to do something good might help bring about that good thing. But if the campaign fails, that donation accomplished basically nothing. Existential risk mitigation efforts (as such) only do any good if they work. If the world ends anyway, that effort didn't actually accomplish anything. Plenty of interventions can also backfire. Some interventions aim to increase or decrease probabilities. There are a lot of ways to mess this up. My least favorite arguments in intro EA messaging historically were things like: "even if the chance of [EVENT] is quite low, say 1%, then ...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Kidney stone pain as a potential cause area, published by Dan Elton on May 3, 2022 on The Effective Altruism Forum. This is a cross-post from my Substack (original post here). Note: At the Effective Altruism Global: San Francisco conference in 2017, Prof. Will MacAskill implored the audience to “keep EA weird”. As the EA movement grows, it's important to keep EA's original spirit of exploration alive. To help do that, I'm planning to write several articles on potential new — and weird — cause areas. Effective altruists want to figure out how to do the most good per dollar spent. “Good” is often cached out in terms of deaths prevented or quality-adjusted life years saved (QALYs). QALYs attempt to adjust life-years for different states of health. However, the very method of QALY calculation, which typically involves surveys asking about trade-offs, might have some blind spots. For instance, if a disease state is rare, than most likely the requisite survey data for it has never been collected. The surveys themselves may have blind spots too. Consider these points from Andrés Gómez Emilsson (emphasis mine): “Someone described the experience of having a kidney stone as ‘indistinguishable from being stabbed with a white-hot-glowing knife that's twisted into your insides non-stop for hours'. It's likely that the reason why we do not hear about this is because (1) trauma often leads to suppressed memories, (2) people don't like sharing their most vulnerable moments, and (3) memory is state-dependent (you cannot easily recall the pain of kidney stones .. you've lost a tether/handle/trigger for it, as it is an alien state-space on a wholly different scale of intensity than everyday life).” Andres Gomez Emilsson As Daniel Kahneman describes in his book Thinking Fast and Slow, the remembering self is different than the experiencing self. People have trouble describing and conceptualizing extreme events, either positive or negative. People also don't like thinking about extreme negative events generally, whether they experienced them or others did. I personally sometimes notice my brain flinching away when thinking about kidney stone pain, even though I haven't experienced it myself. In the first part of this post I'll go over the evidence for extreme pain events. Then, I'll focus on kidney stones. The main reason for focusing on kidney stone pain is that over the past two years I've worked off-an-on on automated deep learning based software for detecting and measuring kidney stones in CT scans (see my paper in Medical Physics). So I have some expertise on the subject. Currently I am working with a radiologist at Massachusetts General Hopsital who is an expert on stone disease, Prof. Avinash Kambadakone. Background - suffering focused ethics “In my opinion human suffering makes a direct moral appeal, namely, the appeal for help, while there is no similar call to increase the happiness of a man who is doing well anyway.” “Instead of the greatest happiness for the greatest number, one should demand, more modestly, the least amount of avoidable suffering for all.”— Karl Popper, The Open Society and Its Enemies (1945) The idea that we should focus on eliminating suffering over increasing pleasure is intuitive to many people. See this recent Twitter poll from Robin Hanson: So, I don't think I need to spend much time here convincing people that reducing suffering should take precedent over increasing happiness. Note what I have in mind here is what is called “weakly-negative utilitarianism” which is quite different than pure negative utilitarianism, which focuses only on eliminating suffering. Readers interested in diving further into these topics should check out Lukas Gloor's essay “The Case for Suffering-Focused Ethics”. Background - long-tailed distributions of pleasure and pain “...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: EA and Global Poverty. Let's Gather Evidence, published by Nathan Young on April 5, 2022 on The Effective Altruism Forum. There was a recent discussion on twitter about whether global development had been deprioritised within EA. This struck a chord with some (edit despite the claim in the twitter thread being false). So: What is the priority of Global poverty within EA, compared to where it ought to be? I am going to post some data and some theories. I'd like if people in the comments falsified them and then we'd know the answer. Some people seem to think that global development is lower priority than it should be within EA. Is this view actually widespread? Global poverty was held in very high esteem in 2020. Without further evidence we should assume it still is. In the 2020 survey, no cause area had a higher average rating (I'm eyeballing this graph) or a higher % of near top + top priority ratings. In 2020, global development was considered the highest priority by EAs in general. Global poverty gets the most money by cause area from Open Phil & GWWC according to/ The FTX future fund lists economic growth as one of its areas of interest (/) Theory: Elite EA conversation discusses global poverty less than AI or animal welfare. What is the share of cause areas among forum posts, 80k episodes or EA tweets? I'm sure some of this information is trivial for one of you to find. Is this theory wrong? Theory: Global poverty work has ossified around GiveWell and their top charities. Jeff Mason and Yudkowsky both made variations of this point. Yudkowsky's reasoning was that risktakers hadn't been in global poverty research anyway - it attracted a more conservative kind of person. I don't know how to operationalise thoughts against this, but maybe one of you can. Personally, I think that many people find global poverty uniquely compelling. It's unarguably good. You can test it. It has quick feedback loops (compared to many other cause areas). I think it's good to be in coalition with the most effective area of an altruistic space that vibes with so many people. I like global poverty as a key concern (even though it's not my key concern) because I like good coalitional partners. And Longtermist and global development EAs seem to me to be natural allies. I can also believe that if we care about the lives of people currently alive in the developing world and have AI timelines of less than 20 years, we shouldn't focus on global development. I'm not an expert here and this view makes me uncomfortable, but conditional on short AI timelines, I can't find fault with it. In terms of QALYs there may be more risk to the global poor from AI than malnourishment. If this is the case, EA would moves away from being divided by cause areas towards a primary divide of "AI soon" vs "AI later" (though deontologists might argue it's still better to improve people's lives now rather than save them from something that kills all of us). Feel fry to suggest flaws in this argument I'm going to seed a few replies in the comments. I know some of you hate it when I do this, but please bear with me. What do you think? What are the facts about this? endnote: I predict 50% that this discussion won't work, resolved by me in two weeks. I think that people don't want to work together to build a sort of vague discussion on the forum. We'll see. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Announcing the actual longtermist incubation program, published by GidonKadosh on April 1, 2022 on The Effective Altruism Forum. It is often discussed that EA is talent-constrained, and the movement is experimenting with ways to create new leaders for the most pressing cause areas. Since the launch of Naming What We Can, our linguistically-talented team conducted in-depth analysis in search of the most promising and neglected opportunities within this space. Our analysis shows that even though incubation programs are considered outside EA to be one the most promising ways to foster new talent, there is not a single incubation program within the EA ecosystem. Project Plan The first, and hardest part of the program, is finding strong applicants. The incubator participants would stay in the incubator facility for ~18 years and will be able to learn about EA and develop domain expertise. The new people incubated at our incubator will be called X-risk-Men. At some part of their growth, each X-risk-Man would realize they have an EA-superpower. Some will be super-forecasters. Others will be able to create QALYs out of thin air. In the most extreme cases, some might even be able to discuss Roko's Basilisk without putting everyone close to them in danger. When their incubation is over, the X-risk-Men will all be automatically accepted to Charity Entrepreneurship (or has been renamed by Naming What We Can - Charity Entreprenreurooshrimp) and start super-effective charities. As others have noted, “EA should focus on being a really good place for a relatively small group of unusual people to try to be extremely impactful”. And there is nothing weirder than superpowers, which definitely have not gone mainstream. Impact estimation Overall, we think the impact of the project will be net negative on expectation (see our Guesstimate model). That is because we think that the impact is likely to be somewhat positive, but there is a really small tail risk that we will cause the termination of the EA movement. However, as we are risk-averse we can mostly ignore high tails in our impact assessment so there is no need to worry. Call to Action In order to begin the incubation program, we need local EA groups to identify members with unusual talents or who are otherwise strange. We expect that very few EAs are strange, so this may be difficult, but with effort, we think that most EA groups (and maybe some EA orgs) can identify at least one such member and nominate them in a comment below. Once all members are chosen, we will secretly clone them and raise the clones in the new actual incubator. Many thanks to David Manheim, Guy Raveh, Omri Sheffer, Edo Arad, and Yuval Shapira for contributing to this new important project, as well as many members of EA Israel (some of them have actually been through the trials in the Israeli desert). Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Brain preservation to prevent involuntary death: a possible cause area, published by Andy McKenzie on March 22, 2022 on LessWrong. (Cross-posted at the Effective Altruism Forum) Previous EA discussions of this topic: here, here, here, and here. Note that these primarily focus on cryonics, although I prefer the term brain preservation because it is also compatible with non-cryogenic methods and anchors the discussion around the preservation quality of the brain. See here for more discussion of terminology. This post is split up into two sections: (a) Technical aspects, which discusses why I think preserving brains with methods available today may allow for revival in the future with long-term memories and personality traits intact. (b) Ethical aspects, which discusses why I think the field may be among the most cost-effective ways to convert money into long-term QALYs, given certain beliefs and values. In this post, I'm not discussing whether individuals should sign themselves up for brain preservation, but rather whether it is a good use of altruistic resources to preserve people and perform research about brain preservation. Technical aspects of brain preservation 1. What is the idea behind brain preservation? a. Brain preservation is the process of carefully preserving and protecting the information in someone's brain for an indefinite length of time, with the goal of reviving them if technologic and civilizational capacity ever progresses to the point where it is feasible and humane to do so. b. Our society's definition of death has shifted over time. It depends upon the available medical technology, such as CPR and artificial respiration. In the future, the definition of death will almost certainly be different than it is today. One possible improved definition of death would be when the information in the person's brain that they value is irreversibly lost, which is known as information-theoretic death. c. Pausing life without causing information-theoretic death could be done with a long-term preservation method that is not yet known to be reversible today, but which has the goal of preserving enough information in the brain so that it could potentially become reversible in the future with improvements in technology. This is brain preservation. d. With current methods, we can potentially preserve enough structure in the brain over the long term to retain the information for valued cognitive functions like long-term memories. There are multiple possible methods to attempt to accomplish this, each with upsides and downsides. e. Plausible methods for the revival of people following brain preservation include whole brain emulation or off-board molecular nanotechnology-based repair. 2. What in the brain is necessary to try to preserve? a. It is already possible to stop electrochemical neuronal activity (in humans) and biological time (in other animals) without loss of long-term memories. The cognitive functions that most people care about seem to be encoded by static structures in the brain. More on this here. b. Adequately preserving the brain alone would be enough to retain the information for long-term memories and core personality traits, because it is the only part of the body that is known to be irreplaceable without massive effects on this information. More on this here. c. Despite currently lacking complete models, we can use existing knowledge in neuroscience to evaluate the hypothetical process by which structural information for valued cognitive functions could be mapped in the future. More on this here. d. A wealth of evidence suggests engrams are encoded in neural structures distributed across the brain. More specifically, it seems to be the distributed activity of neuronal ensembles communicating through the biomolecule-annotated connectome that instant...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Brain preservation to prevent involuntary death: a possible cause area, published by Andy McKenzie on March 22, 2022 on LessWrong. (Cross-posted at the Effective Altruism Forum) Previous EA discussions of this topic: here, here, here, and here. Note that these primarily focus on cryonics, although I prefer the term brain preservation because it is also compatible with non-cryogenic methods and anchors the discussion around the preservation quality of the brain. See here for more discussion of terminology. This post is split up into two sections: (a) Technical aspects, which discusses why I think preserving brains with methods available today may allow for revival in the future with long-term memories and personality traits intact. (b) Ethical aspects, which discusses why I think the field may be among the most cost-effective ways to convert money into long-term QALYs, given certain beliefs and values. In this post, I'm not discussing whether individuals should sign themselves up for brain preservation, but rather whether it is a good use of altruistic resources to preserve people and perform research about brain preservation. Technical aspects of brain preservation 1. What is the idea behind brain preservation? a. Brain preservation is the process of carefully preserving and protecting the information in someone's brain for an indefinite length of time, with the goal of reviving them if technologic and civilizational capacity ever progresses to the point where it is feasible and humane to do so. b. Our society's definition of death has shifted over time. It depends upon the available medical technology, such as CPR and artificial respiration. In the future, the definition of death will almost certainly be different than it is today. One possible improved definition of death would be when the information in the person's brain that they value is irreversibly lost, which is known as information-theoretic death. c. Pausing life without causing information-theoretic death could be done with a long-term preservation method that is not yet known to be reversible today, but which has the goal of preserving enough information in the brain so that it could potentially become reversible in the future with improvements in technology. This is brain preservation. d. With current methods, we can potentially preserve enough structure in the brain over the long term to retain the information for valued cognitive functions like long-term memories. There are multiple possible methods to attempt to accomplish this, each with upsides and downsides. e. Plausible methods for the revival of people following brain preservation include whole brain emulation or off-board molecular nanotechnology-based repair. 2. What in the brain is necessary to try to preserve? a. It is already possible to stop electrochemical neuronal activity (in humans) and biological time (in other animals) without loss of long-term memories. The cognitive functions that most people care about seem to be encoded by static structures in the brain. More on this here. b. Adequately preserving the brain alone would be enough to retain the information for long-term memories and core personality traits, because it is the only part of the body that is known to be irreplaceable without massive effects on this information. More on this here. c. Despite currently lacking complete models, we can use existing knowledge in neuroscience to evaluate the hypothetical process by which structural information for valued cognitive functions could be mapped in the future. More on this here. d. A wealth of evidence suggests engrams are encoded in neural structures distributed across the brain. More specifically, it seems to be the distributed activity of neuronal ensembles communicating through the biomolecule-annotated connectome that instant...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Brain preservation to prevent involuntary death: a possible cause area, published by AndyMcKenzie on March 22, 2022 on The Effective Altruism Forum. Previous EA discussions of this topic: here, here, here, and here. Note that these primarily focus on cryonics, although I prefer the term brain preservation because it is also compatible with non-cryogenic methods and anchors the discussion around the preservation quality of the brain. See here for more discussion of terminology. This post is split up into two sections: (a) Technical aspects, which discusses why I think preserving brains with methods available today may allow for revival in the future with long-term memories and personality traits intact. (b) Ethical aspects, which discusses why I think the field may be among the most cost-effective ways to convert money into long-term QALYs, given certain beliefs and values. In this post, I'm not discussing whether individuals should sign themselves up for brain preservation, but rather whether it is a good use of altruistic resources to preserve people and perform research about brain preservation. Technical aspects of brain preservation 1. What is the idea behind brain preservation? a. Brain preservation is the process of carefully preserving and protecting the information in someone's brain for an indefinite length of time, with the goal of reviving them if technologic and civilizational capacity ever progresses to the point where it is feasible and humane to do so. b. Our society's definition of death has shifted over time. It depends upon the available medical technology, such as CPR and artificial respiration. In the future, the definition of death will almost certainly be different than it is today. One possible improved definition of death would be when the information in the person's brain that they value is irreversibly lost, which is known as information-theoretic death. c. Pausing life without causing information-theoretic death could be done with a long-term preservation method that is not yet known to be reversible today, but which has the goal of preserving enough information in the brain so that it could potentially become reversible in the future with improvements in technology. This is brain preservation. d. With current methods, we can potentially preserve enough structure in the brain over the long term to retain the information for valued cognitive functions like long-term memories. There are multiple possible methods to attempt to accomplish this, each with upsides and downsides. e. Plausible methods for the revival of people following brain preservation include whole brain emulation or off-board molecular nanotechnology-based repair. 2. What in the brain is necessary to try to preserve? a. It is already possible to stop electrochemical neuronal activity (in humans) and biological time (in other animals) without loss of long-term memories. The cognitive functions that most people care about seem to be encoded by static structures in the brain. More on this here. b. Adequately preserving the brain alone would be enough to retain the information for long-term memories and core personality traits, because it is the only part of the body that is known to be irreplaceable without massive effects on this information. More on this here. c. Despite currently lacking complete models, we can use existing knowledge in neuroscience to evaluate the hypothetical process by which structural information for valued cognitive functions could be mapped in the future. More on this here. d. A wealth of evidence suggests engrams are encoded in neural structures distributed across the brain. More specifically, it seems to be the distributed activity of neuronal ensembles communicating through the biomolecule-annotated connectome that instantiates long-term memory recall...

How does GiveWell's approach to charity differ from other charitable organizations? Why does GiveWell list such a small number of recommended charities? How does GiveWell handle the fact that different moral frameworks measure causes differently? Why has GiveWell increased its preference for health-related causes over time? How does GiveWell weight QALYs and DALYs? How much does GiveWell rely on a priori moral philosophy versus people's actual moral intuitions? Why does GiveWell have such low levels of confidence in some of its most highly-recommended charities or interventions? What should someone do if they want to be more confident that their giving is actually having a positive impact? Why do expected values usually tend to drop as more information is gathered? How does GiveWell think about second-order effects? How much good does the median charity do? Why is it so hard to determine how impactful charities are? Many charities report on the effectiveness of individual projects, but why don't more of them report on their effectiveness overall as an organization? Venture capitalists often diversify their portfolios as much as possible because they know that, even though most startups will fail, one unicorn can repay their investments many times over; so, in a similar way, why doesn't GiveWell fund as many projects as possible rather than focusing on a few high performers? Why doesn't GiveWell recommend more animal charities? Does quantification sometimes go too far?Elie Hassenfeld co-founded GiveWell in 2007 and currently serves as its CEO. He is responsible for setting GiveWell's strategic vision and has grown the organization into a leading funder in global health and poverty alleviation, directing over $500 million annually to high-impact giving opportunities. Since 2007, GiveWell has directed more than $1 billion to outstanding charities. Elie co-led the development of GiveWell's research methodology and guides the research team's agenda. He has also worked closely with donors to help them define their giving strategies and invest toward them. Prior to founding GiveWell, Elie worked in the hedge fund industry. He graduated from Columbia University in 2004 with a B.A. in religion.{% include partials/ukraine.md %}

Read the full transcriptHow does GiveWell's approach to charity differ from other charitable organizations? Why does GiveWell list such a small number of recommended charities? How does GiveWell handle the fact that different moral frameworks measure causes differently? Why has GiveWell increased its preference for health-related causes over time? How does GiveWell weight QALYs and DALYs? How much does GiveWell rely on a priori moral philosophy versus people's actual moral intuitions? Why does GiveWell have such low levels of confidence in some of its most highly-recommended charities or interventions? What should someone do if they want to be more confident that their giving is actually having a positive impact? Why do expected values usually tend to drop as more information is gathered? How does GiveWell think about second-order effects? How much good does the median charity do? Why is it so hard to determine how impactful charities are? Many charities report on the effectiveness of individual projects, but why don't more of them report on their effectiveness overall as an organization? Venture capitalists often diversify their portfolios as much as possible because they know that, even though most startups will fail, one unicorn can repay their investments many times over; so, in a similar way, why doesn't GiveWell fund as many projects as possible rather than focusing on a few high performers? Why doesn't GiveWell recommend more animal charities? Does quantification sometimes go too far?Elie Hassenfeld co-founded GiveWell in 2007 and currently serves as its CEO. He is responsible for setting GiveWell's strategic vision and has grown the organization into a leading funder in global health and poverty alleviation, directing over $500 million annually to high-impact giving opportunities. Since 2007, GiveWell has directed more than $1 billion to outstanding charities. Elie co-led the development of GiveWell's research methodology and guides the research team's agenda. He has also worked closely with donors to help them define their giving strategies and invest toward them. Prior to founding GiveWell, Elie worked in the hedge fund industry. He graduated from Columbia University in 2004 with a B.A. in religion.

Read the full transcript here. How does GiveWell's approach to charity differ from other charitable organizations? Why does GiveWell list such a small number of recommended charities? How does GiveWell handle the fact that different moral frameworks measure causes differently? Why has GiveWell increased its preference for health-related causes over time? How does GiveWell weight QALYs and DALYs? How much does GiveWell rely on a priori moral philosophy versus people's actual moral intuitions? Why does GiveWell have such low levels of confidence in some of its most highly-recommended charities or interventions? What should someone do if they want to be more confident that their giving is actually having a positive impact? Why do expected values usually tend to drop as more information is gathered? How does GiveWell think about second-order effects? How much good does the median charity do? Why is it so hard to determine how impactful charities are? Many charities report on the effectiveness of individual projects, but why don't more of them report on their effectiveness overall as an organization? Venture capitalists often diversify their portfolios as much as possible because they know that, even though most startups will fail, one unicorn can repay their investments many times over; so, in a similar way, why doesn't GiveWell fund as many projects as possible rather than focusing on a few high performers? Why doesn't GiveWell recommend more animal charities? Does quantification sometimes go too far?Elie Hassenfeld co-founded GiveWell in 2007 and currently serves as its CEO. He is responsible for setting GiveWell's strategic vision and has grown the organization into a leading funder in global health and poverty alleviation, directing over $500 million annually to high-impact giving opportunities. Since 2007, GiveWell has directed more than $1 billion to outstanding charities. Elie co-led the development of GiveWell's research methodology and guides the research team's agenda. He has also worked closely with donors to help them define their giving strategies and invest toward them. Prior to founding GiveWell, Elie worked in the hedge fund industry. He graduated from Columbia University in 2004 with a B.A. in religion.[Read more]

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Replacing micromarriages, published by Richard Ngo on March 11, 2022 on LessWrong. tl;dr micromarriages are ill-defined, and not analogous to micromorts. I recommend using QAWYs (Quality-adjusted Wife Years) instead, where 1 QAWY is an additional year of happy marriage. I once compiled a list of concepts which I'd discovered were much less well-defined than I originally thought. I'm sad to say that I now have to add Chris Olah's micromarriages to the list. In his words: “Micromarriages are essentially micromorts, but for marriage instead of death. A micromarriage is a one in a million chance that an action will lead to you getting married, relative to your default policy.” It's a fun idea, and sometimes helpful in deciding when to go to various events. But upon thinking about it more, I've realised that the analogy doesn't quite work. The key difference is that micromorts are a measure of acute risk - i.e. immediate death. For activities like skydiving, this is the main thing to worry about, so it's a pretty good metric. But most actions we'd like to measure using micromarriages (going to a party, say, or working out more) won't lead you to get married immediately - instead they flow through to affect marriages that might happen at some later point. So how can we measure the extent to which an action affects your future marriages, even in theory? One option is to track how it changes the likelihood you'll get married eventually. But this is pretty unhelpful. By analogy, if micromorts measured an action's effect on the probability that you'd die eventually, then all actions would have almost zero micromorts (with the possible exception of some life-extension work during the last few decades). Similarly, under this definition the micromarriages you gain from starting a new relationship could be mostly cancelled out by the fact that this relationship cuts off other potential relationships. An alternative is to measure actions not by how much they change the probability that you'll get married eventually, but by how much you expect them to causally contribute to an eventual marriage. The problem there is that many actions can causally contribute to a marriage (meeting someone, asking them out, proposing, etc) and there's no principled way of splitting the credit between them. I won't go into the details here, but the basic problem is the same as one which arises when trying to allocate credit to multiple contributors to a charitable intervention. E.g. if three different funders are all necessary for getting a project off the ground, in some sense they can all say that they “caused” the project to happen, but that would end up triple-counting their total impact. (In this case, we can use Shapley values to allocate credit - but the boundaries between different “actions” are much more arbitrary than the boundaries between different “agents”, making it harder to apply Shapley values to the micromarriage case. Should we count the action “skipping meeting someone else” as a contributor to the marriage? Or the action “turning your head to catch sight of them”? This is basically a rabbit-hole without end - and that's not even getting into issues of marriage identity across possible worlds.) Fortunately, however, there's another approach which does work. When thinking about mortality, the medical establishment doesn't just measure acute risks, but also another category of risk: chronic risks, like smoking. When smoking, you don't get a binary outcome after each cigarette, but rather a continual degradation of health. So chronic risks are instead measured in terms of the expected decrease in your lifespan - for example, with units of microlives, where one microlife is one millionth of an adult lifespan (about half an hour); or with quality-adjusted life years (QALYs), to adjust fo...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Replacing micromarriages, published by Richard Ngo on March 11, 2022 on LessWrong. tl;dr micromarriages are ill-defined, and not analogous to micromorts. I recommend using QAWYs (Quality-adjusted Wife Years) instead, where 1 QAWY is an additional year of happy marriage. I once compiled a list of concepts which I'd discovered were much less well-defined than I originally thought. I'm sad to say that I now have to add Chris Olah's micromarriages to the list. In his words: “Micromarriages are essentially micromorts, but for marriage instead of death. A micromarriage is a one in a million chance that an action will lead to you getting married, relative to your default policy.” It's a fun idea, and sometimes helpful in deciding when to go to various events. But upon thinking about it more, I've realised that the analogy doesn't quite work. The key difference is that micromorts are a measure of acute risk - i.e. immediate death. For activities like skydiving, this is the main thing to worry about, so it's a pretty good metric. But most actions we'd like to measure using micromarriages (going to a party, say, or working out more) won't lead you to get married immediately - instead they flow through to affect marriages that might happen at some later point. So how can we measure the extent to which an action affects your future marriages, even in theory? One option is to track how it changes the likelihood you'll get married eventually. But this is pretty unhelpful. By analogy, if micromorts measured an action's effect on the probability that you'd die eventually, then all actions would have almost zero micromorts (with the possible exception of some life-extension work during the last few decades). Similarly, under this definition the micromarriages you gain from starting a new relationship could be mostly cancelled out by the fact that this relationship cuts off other potential relationships. An alternative is to measure actions not by how much they change the probability that you'll get married eventually, but by how much you expect them to causally contribute to an eventual marriage. The problem there is that many actions can causally contribute to a marriage (meeting someone, asking them out, proposing, etc) and there's no principled way of splitting the credit between them. I won't go into the details here, but the basic problem is the same as one which arises when trying to allocate credit to multiple contributors to a charitable intervention. E.g. if three different funders are all necessary for getting a project off the ground, in some sense they can all say that they “caused” the project to happen, but that would end up triple-counting their total impact. (In this case, we can use Shapley values to allocate credit - but the boundaries between different “actions” are much more arbitrary than the boundaries between different “agents”, making it harder to apply Shapley values to the micromarriage case. Should we count the action “skipping meeting someone else” as a contributor to the marriage? Or the action “turning your head to catch sight of them”? This is basically a rabbit-hole without end - and that's not even getting into issues of marriage identity across possible worlds.) Fortunately, however, there's another approach which does work. When thinking about mortality, the medical establishment doesn't just measure acute risks, but also another category of risk: chronic risks, like smoking. When smoking, you don't get a binary outcome after each cigarette, but rather a continual degradation of health. So chronic risks are instead measured in terms of the expected decrease in your lifespan - for example, with units of microlives, where one microlife is one millionth of an adult lifespan (about half an hour); or with quality-adjusted life years (QALYs), to adjust fo...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Five steps for quantifying speculative interventions, published by NunoSempere on February 18, 2022 on The Effective Altruism Forum. Summary Currently, we can't compare the impact of speculative interventions in a principled way. When making a decision about where to work or donate, longtermists or risk-neutral neartermists may have to choose an organization based on status, network effects, or expert opinion. This is, obviously, not ideal. I propose a simple solution, if not an easy one. First, estimate the impact of an intervention in narrow units (such as micro-covids, or estimates of research quality). Then, convert those narrow units to more and more general units (such as QALYs, or percentage reduction in x-risk). Quantifying the value of speculative interventions to a standard similar to GiveWell's represents a lot of work on a messy problem. In this post, I'll break it down to these five steps: Create narrow units for specific types of interventions Use narrow units to evaluate interventions Create more general units, and conversion factors from narrow units to general units Resolve or quantify crucial considerations in order to generalize further Scale-up evaluations: do more evaluations, better, more cheaply, about more things. As we make progress on these subproblems, relative value comparisons would become more robust, principled and transparent, which would improve the quality of our decision-making around funding and prioritization. Decisions about where to work or where to donate might still be informed by some subjective factors (e.g., personal fit, value differences), but they would be more grounded in research and expected utility calculations. This proposal grew out of my frustrations with quantitatively evaluating longtermist organizations or EA projects more generally without a developed framework. Nobody has really been doing this kind of evaluation, so the infrastructure and know-how is just not there. It's not even clear what the bar for funding longtermist interventions should be–we don't know how much good "the last longtermist dollar" will accomplish. Without that key number, funders have to make grants to the best of their abilities by using heuristics and intuitions, which naturally has limitations. It has been argued that expected utility calculations can be misleading or counter-productive. But these calculations don't have to be perfect, they just have to be better than the alternative—whatever non-quantitative methods people would have used instead. It also doesn't matter in practice whether one can reach expected value calculations in all their glory, as long as the efforts towards quantification end up paying off (e.g., in terms of better decisions). So from my perspective, one of the most powerful tools in the EA arsenal has been left gathering dust, mostly for unclear reasons. In the short term, intuition or heuristics can fill in the gap. But in the long term, as EA moves billions of additional dollars, we will need to upgrade intuition-based human factors to auditable, scalable and more powerful evaluation methods. Step 1: Create narrow units for specific types of interventions The simplest and cheapest way to start seems with units tailored to one particular intervention or type of intervention. I'm going to call these “narrow units”, as opposed to more general (e.g., QALYs, which could denominate many types of interventions) or abstract ones (e.g., measures of “research value”). With narrow units, we can ask if a unit captures most of what we care about in an intervention, and evaluate a new unit on that metric. In the case of research at EA organizations, we care about how it directly influences decisions, but also about the further research it enables, the mentorship around it, the prestige that the authors attain, etc. A un...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: (briefly) RaDVaC and SMTM, two things we should be doing, published by Eliezer Yudkowsky on January 12, 2022 on LessWrong. Having not apparently the energy to write this longly, I write it shortly instead, that it be written at all. People sometimes go about saying now, in this community, that there is collectively enough money that we could potentially go do more things with it, if there were things worth doing. If that's true, I'd like to see us planting seed grains now for replacing the now-defunct state capacity of the USA and Earth, with respect to biodefense and ultra-high-leverage med R&D. As a poster child of a previous intervention I backed here, Seasonal Affective Disorder affects 0.5%-3% of the population and higher in countries at extreme latitudes. Call it a hundred million people at a guess. Standard lightboxes don't work very well for treating it. The Sun works great for treating it. Reason suggests trying more light. Earth, however, previously lacked the state capacity to investigate this obvious question of massive scope. I put a private funder in touch with a group that did a preliminary investigation; they need to run a larger study but preliminary results suggest that they may, in fact, need to use more light and that doing so might be effective. Again, that's for a problem that probably over a hundred million people have. So it's not very surprising that investigation of it bottlenecks on there being a single interested medical researcher, who writes Eliezer Yudkowsky as the person who posed that question, and gets funding arranged by that route. It was less than $100,000. This sort of thing seems obviously competitive to me with QALYs/$ or DALYs/$ on global poverty interventions. Really obviously competitive, actually. I will not argue the point further because I expect that most readers who can be persuaded found a glance at the numbers sufficient. EA's ability to do more things in this space, if it is not bottlenecked on money, is very likely bottlenecked on: good ideas to pursue; people who can pursue those ideas; and/or admin staff who can investigate grants, make them, and operate them. I suspect that people who can do these things are, at the very least, valuable. They should therefore be nurtured even in their earlier stages. If you ever want an apple tree that bears fruit, you may need to at some point plant a seed that doesn't have any apples on it right then, and invest effort into watering it in proportion to how many apples you hope for later, rather than how much this tiny sapling has proven itself right now. I think it was a huge, huge mistake that more money was not spent on AGI alignment when it was small and weird and unproven. The resulting damage was not something that could be fixed by any or all of the money that became available later. Someday I may write more about this. Anyways, don't do that. The Rapid Deployment Vaccine Collaborative, aka RaDVaC, is now past the small weird stage. They've pretty much proved themselves. They should be nurtured and scaled up to where they can start to replace US and Earth defunct state capacity to do the R&D that leads up to being able to rapidly design new vaccines that rapidly scale in production and deployment. If we can't give RaDVaC $2M I'd like to know what it's being spent on that's more important. Covid-19 was not very much of a pandemic and if Earth ran into a serious pandemic in its current state that would be a serious problem. Some weird person [correction: 2 weird people] wants to investigate whether the real driver of our massive planetwide obesity epidemic is lithium contamination, probably in water. If you are completely unfamiliar with the actual science on obesity you probably think that's dumb because obesity is caused by high-palatability foods. Read the first page lin...

Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: (briefly) RaDVaC and SMTM, two things we should be doing, published by Eliezer Yudkowsky on January 12, 2022 on LessWrong. Having not apparently the energy to write this longly, I write it shortly instead, that it be written at all. People sometimes go about saying now, in this community, that there is collectively enough money that we could potentially go do more things with it, if there were things worth doing. If that's true, I'd like to see us planting seed grains now for replacing the now-defunct state capacity of the USA and Earth, with respect to biodefense and ultra-high-leverage med R&D. As a poster child of a previous intervention I backed here, Seasonal Affective Disorder affects 0.5%-3% of the population and higher in countries at extreme latitudes. Call it a hundred million people at a guess. Standard lightboxes don't work very well for treating it. The Sun works great for treating it. Reason suggests trying more light. Earth, however, previously lacked the state capacity to investigate this obvious question of massive scope. I put a private funder in touch with a group that did a preliminary investigation; they need to run a larger study but preliminary results suggest that they may, in fact, need to use more light and that doing so might be effective. Again, that's for a problem that probably over a hundred million people have. So it's not very surprising that investigation of it bottlenecks on there being a single interested medical researcher, who writes Eliezer Yudkowsky as the person who posed that question, and gets funding arranged by that route. It was less than $100,000. This sort of thing seems obviously competitive to me with QALYs/$ or DALYs/$ on global poverty interventions. Really obviously competitive, actually. I will not argue the point further because I expect that most readers who can be persuaded found a glance at the numbers sufficient. EA's ability to do more things in this space, if it is not bottlenecked on money, is very likely bottlenecked on: good ideas to pursue; people who can pursue those ideas; and/or admin staff who can investigate grants, make them, and operate them. I suspect that people who can do these things are, at the very least, valuable. They should therefore be nurtured even in their earlier stages. If you ever want an apple tree that bears fruit, you may need to at some point plant a seed that doesn't have any apples on it right then, and invest effort into watering it in proportion to how many apples you hope for later, rather than how much this tiny sapling has proven itself right now. I think it was a huge, huge mistake that more money was not spent on AGI alignment when it was small and weird and unproven. The resulting damage was not something that could be fixed by any or all of the money that became available later. Someday I may write more about this. Anyways, don't do that. The Rapid Deployment Vaccine Collaborative, aka RaDVaC, is now past the small weird stage. They've pretty much proved themselves. They should be nurtured and scaled up to where they can start to replace US and Earth defunct state capacity to do the R&D that leads up to being able to rapidly design new vaccines that rapidly scale in production and deployment. If we can't give RaDVaC $2M I'd like to know what it's being spent on that's more important. Covid-19 was not very much of a pandemic and if Earth ran into a serious pandemic in its current state that would be a serious problem. Some weird person [correction: 2 weird people] wants to investigate whether the real driver of our massive planetwide obesity epidemic is lithium contamination, probably in water. If you are completely unfamiliar with the actual science on obesity you probably think that's dumb because obesity is caused by high-palatability foods. Read the first page lin...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Introducing Effective Self-Help, published by Ben Williamson on January 6, 2022 on The Effective Altruism Forum. Effective Self-Help (ESH) is a pilot initiative researching the most effective ways people can improve their wellbeing and productivity. This post explains what Effective Self-Help is, what I hope the project can achieve, and why I believe this work may be highly impactful. As this is a long post, I suggest reading the Summary section below and then skipping to whatever sections seem of greatest interest. Based on rough Fermi calculations made using Guesstimate, I estimate a mean impact per Effective Self-Help article of 180 hours of high-impact work and 4.2 QALYs. However, these numbers are very uncertain and best taken as an indication that ESH could be highly impactful and cost-effective, rather than a signal that it will be. Thank you to the many people who have discussed ideas, critiqued drafts, and provided invaluable insights in recent weeks. This project has received initial funding from the EA Infrastructure Fund. Summary Effective Self-Help is currently an ongoing series of articles on relevant topics posted to the EA Forum. I intend to develop the project into a home for the best guidance on how individuals can improve their wellbeing and productivity. The project is currently solely the work of me, Ben Williamson, with feedback, comments, and ideas from lots of other lovely people involved in EA. In the What is Effective Self-Help? section, I discuss how I think ESH can be unique as a self-help resource by combining several key components: Prioritisation: Highlighting the most effective interventions and how effective they are, rather than just listing interventions that may be effective. Research Quality: Providing more rigorous and well-rounded advice that combines the findings of scientific literature with more Bayesian forms of evidence. Presentation: Maximising engagement through curated recommendations and the use of digital media (video, audio, and interactive programmes). Breadth: Covering topics across the full breadth of wellbeing and productivity, rather than just specific domains of expertise. Practicality: A focus on enabling behaviour change by highlighting practical actions and tailoring content to maximise the success of habit adoption. Positive mental health: Looking at how to improve the wellbeing of people who are not struggling with mental health issues as well as those who are. Free Access: Avoiding any influence of paywalls, advertising, or affiliate marketing on the quality of advice provided and full access to advice. Under Why Effective Self-Help could be highly impactful, I envisage three main routes to impact which are discussed in greater depth in the ‘Theory of Change' sections. These are: Increasing the productivity of people doing high-impact work Helping a large audience make small improvements to their wellbeing Attracting new people to the EA community through an interest in self-improvement. I created Guesstimate models for the first two of these routes to impact, producing best-guess estimates that ESH could add 180 hours of productive work and 4.2 QALYs per article. However, these results are highly uncertain and best interpreted as an indication that ESH has the potential to be highly impactful if things go well, rather than a strong endorsement that it will be. Downside risks and arguments for ESH being ineffective discusses a range of ways in which Effective Self-Help could be of limited value or of active harm. The main downside risks discussed are that ESH could: Give advice that is of net harm by badly accounting for risks and side-effects Serve as a weak introduction to EA Make the EA community more insular. The main ways listed for how that Effective Self-Help could be of limited effectiveness are: S...

welcome to the nonlinear library, where we use text-to-speech software to convert the best writing from the rationalist and ea communities into audio. this is: Illegible impact is still impact, published by G Gordon Worley III on the effective altruism forum. Write a Review In EA we focus a lot on legible impact. At a tactical level, it's the thing that often separates EA from other altruistic efforts. Unfortunately I think this focus on impact legibility, when taken to extremes and applied in situations where it doesn't adequately account for value, leads to bad outcomes for EA and the world as a whole. Legibility is the idea that only what can easily be explained and measured within a model matters. Anything that doesn't fit neatly in the model is therefore illegible. In the case of impact, legible impact is that which can be measured easily in ways that a model predicts is correlated with outcomes. Examples of legible impact measures for altruistic efforts include counterfactual lives saved, QALYs, DALYs, and money donated; examples of legible impact measures for altruistic individuals include the preceding plus things like academic citations and degrees, jobs at EA organizations, and EA Forum karma. Some impact is semi-legible, like social status among EAs, claims of research progress, and social media engagement. Semi-legible impact either involves fuzzy measurement procedures or low confidence models of how the measure correlates with real world outcomes. Illegible impact is, by comparison, invisible, like helping a friend who, without your help, might have been too depressed to get a better job and donate more money to effective charities or filling a seat in the room at an EA Global talk such that the speaker feels marginally more rewarded for having done the work they are talking about and marginally incentives them to do more. Illegible impact is either hard or impossible to measure or there's no agreed upon model suggesting the action is correlated with impact. And the examples I gave are not maximally illegible because they had to be legible enough for me to explain them to you; the really invisible stuff is like dark matter—we can see signs of its existence (good stuff happens in the world) but we can't tell you much about what it is (no model of how the good stuff happened). The alluring trap is thinking that illegible impact is not impact and that legible impact is the only thing that matters. If that doesn't resonate, I recommend checking out the links above on legibility to see when and how focusing on the legible to the exclusion of the illegible can lead to failure. One place we risk failing to adequately appreciate illegible impact is in work on far future concerns and existential risk. This comes with the territory: it's hard to validate our models of what will happen in the far future, and the feedback cycle is so long that it may be thousands or millions of lifetimes before we get data back that lets us know if an intervention, organization, or person had positive impact, let alone if that impact was effectively generated. Another place we risk impact illegible is in dealing with non-humans since there remains great uncertainty in many people's minds about how to value the experiences of animals, plants, and non-living dynamic systems like AI. Yes, people who care about non-humans are often legible to each other because they share enough assumptions that they can share models and can believe measures in terms of those models, but outside these groups interventions to help non-humans can seem broadly illegible, up to interpreting these the interventions, like those addressing wild animal suffering, as being silly or incoherent rather than potentially positively impactful. Beyond these two examples, there's one place where I think the problems of illegible impact are especially neglected and that is easily tractable if we bother to acknowledge it. It's one EAs are already familiar with, though likely no...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Update from the Happier Lives Institute, published by ClareDonaldson, MichaelPlant on the AI Alignment Forum. Summary This post is an update on the progress and plans of the Happier Lives Institute (HLI), particularly focussing on our ongoing research and projects for the rest of 2020. Our last post on the forum was in June 2019, and our strategy has changed enough since then to warrant a new post. We welcome feedback on our plans. We are a research organisation searching for the most effective methods to improve global well-being. We are doing this by using subjective well-being (SWB) - self-reported happiness and life satisfaction - as the key measure of value in impact evaluation. We think there's a strong theoretical case that SWB is the best way to measure how people's lives go. As effective altruists haven't made much use of this approach, or the existing social science evidence on it, we are exploring what it would look like to do cause prioritisation in terms of SWB. Currently, our two main research projects are: (1) theoretical research into SWB and its measurement, (2) evaluating various life-improving interventions, e.g. cash transfers, in terms of SWB. Our secondary projects explore promising areas when viewed through the SWB lens: (3) evaluating promising mental health programmes, and (4) broad but shallow cause reports into pain, mental health, and positive education. While HLI is interested in mental health, we do not see ourselves as "the EA mental health org”, but as conducting global priorities research. Our three staff members are conducting projects 1 and 2; volunteers are working on projects 3 and 4. We have room for more funding in 2020. Our motivation Many people aligned with effective altruism (EA) aim to maximise well-being. A common approach in impact evaluation is to measure the changes in people's health or wealth and use these as proxies for well-being. For example: the use of disability-adjusted life years (DALYs) and quality-adjusted life years (QALYs) is fairly routine; GiveWell's cost-effectiveness model converts outcomes into the equivalent of doubling consumption and averting the deaths of under-5s. While health and wealth clearly contribute to well-being, few would accept they are, in the end, what ultimately matters (i.e. are intrinsically valuable). Hence, the further challenge is to determine how much impact those, as well as other goods, directly have on well-being, so we can make trade-offs between them. To do this, we could rely on the hypothetical or actual choices that either decision-makers or members of the public make (see some of GiveWell's recent discussion). However, there are several reasons to believe that human biases may lead individuals to make poor assessments (e.g. Wikipedia article on affective forecasting). We do not clearly choose what is best for us. An alternative is to ask people about their lives as they live them. Subjective well-being (SWB) is an umbrella term that includes self-reported life satisfaction and happiness data. We expect most readers would agree that well-being consists in happiness or life satisfaction, at least in part. Research into SWB is rising quickly in academia; over 170,000 books and articles have been published on the topic in the last 15 years (Diener et al., 2018). EA organisations have not (yet) made much use of the existing work on SWB to determine the priorities, and this may lead us to different and surprising conclusions. Therefore, we think that exploring the use of SWB in determining our priorities is a project with high expected value. At HLI, we plan to spend the bulk of our research time over the next year on projects that show how and why subjective well-being can be used to evaluate impact in areas already of interest to EAs, for instance, the effect on SWB from ca...

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: 2020 Top Charity Ideas - Charity Entrepreneurship, published by KarolinaSarek on the AI Alignment Forum. Write a Review This article was also published at Charity Entrepreneurship's blog. We're proud to announce our 2020 Top Charity Ideas! Each year Charity Entrepreneurship identifies highly effective interventions in chosen cause areas. Our Incubation Program gives participants the skills they need to start high-impact nonprofits based on our top intervention recommendations. Our 2020 research period focused on four cause areas: mental health, animal advocacy, family planning, and health & development policy. We began with several hundred ideas in each cause area. Progressive stages of our extensive research process whittled down to eight recommended ideas. Eighty-hour reports linked below illustrate how we came to recommend this year's top interventions. We also provide Incubation Program participants with implementation reports, which provide specific recommendations to map a path forward for a new charity. Our 2020 top recommendations are as follows (in no particular order): MENTAL HEALTH: 1. Guided self-help – Distributing workbooks to enable individuals to work independently on their mental health, supported by short weekly calls from lay health workers. HEALTH & DEVELOPMENT POLICY: 2. Lead paint regulation – Advocating for tighter regulation of lead paint to reduce the burden of lead exposure on human health and economic prosperity. 3. Alcohol regulation – Advocating for increased alcohol taxation to mitigate the harmful effects of consumption. ANIMAL ADVOCACY: 4. Shrimp welfare – Improving the welfare of farmed shrimp, e.g. through collaborating with Vietnamese farmers to better oxygenate the water, thus reducing chronic suffering for shrimp. 5. Feed fortification – Fortifying feed with micronutrients to combat deficiencies and improve the health of laying hens. 6. Ask research – Helping organizations and policy-makers decide what best to ask of the animal agriculture industry. (We explored this intervention during our 2019 research period and passed it on to 2020, as despite its promise it was not started.) FAMILY PLANNING: 7. Mass media campaigns – Broadcasting information about family planning to reduce misconceptions and empower women to make decisions about their fertility. 8. Postpartum family planning – Providing family planning guidance to women at pivotal moments for their health and fertility, such as after giving birth.The above reports are time-capped at eighty hours and follow the chronology of our research process. The reports begin with preliminary research and identifying crucial considerations. Next, we consult with experts. We then create a weighted factor model and a cost-effectiveness analysis. These two methodologies allow us to numerically quantify an intervention; by including both, we balance out their different strengths and weaknesses. Our final section brings together information gained throughout the research process. We have chosen to organize our reports in this way to increase transparency. Readers are able to follow the research as it unfolds and develops, and can see how an idea performs from multiple perspectives. For specific questions on the research process, reach out to Karolina Sarek at karolina@charityscience.com. MENTAL HEALTH Lead researcher: George Bridgwater george@charityscience.com Our four cause areas achieve impact in different ways, so we tailor our metrics accordingly. In this cause area, our cost-effectiveness analyses quantify impact using two metrics: the satisfaction with life scale (SWLS), and quality-adjusted life years (QALYs). We measure the expected number of incremental increases on the SWLS, and of QALYs per dollar spent. We use two metrics because of how difficult it is to capture subjective well-b...

welcome to the nonlinear library, where we use text-to-speech software to convert the best writing from the rationalist and ea communities into audio. This is: Logarithmic Scales of Pleasure and Pain: Rating, Ranking, and Comparing Peak Experiences Suggest the Existence of Long Tails for Bliss and Suffering, published by algekalipso on the effective altruism forum. TL;DR Based on: the characteristic distribution of neural activity, personal accounts of intense pleasure and pain, the way various pain scales have been described by their creators, and the results of a pilot study we conducted which ranks, rates, and compares the hedonic quality of extreme experiences, we suggest that the best way to interpret pleasure and pain scales is by thinking of them as logarithmic compressions of what is truly a long-tail. The most intense pains are orders of magnitude more awful than mild pains (and symmetrically for pleasure). This should inform the way we prioritize altruistic interventions and plan for a better future. Since the bulk of suffering is concentrated in a small percentage of experiences, focusing our efforts on preventing cases of intense suffering likely dominates most utilitarian calculations. An important pragmatic takeaway from this article is that if one is trying to select an effective career path, as a heuristic it would be good to take into account how one's efforts would cash out in the prevention of extreme suffering (see: Hell-Index), rather than just QALYs and wellness indices that ignore the long-tail. Of particular note as promising Effective Altruist careers, we would highlight working directly to develop remedies for specific, extremely painful experiences. Finding scalable treatments for migraines, kidney stones, childbirth, cluster headaches, CRPS, and fibromyalgia may be extremely high-impact (cf. Treating Cluster Headaches and Migraines Using N,N-DMT and Other Tryptamines, Using Ibogaine to Create Friendlier Opioids, and Frequency Specific Microcurrent for Kidney-Stone Pain). More research efforts into identifying and quantifying intense suffering currently unaddressed would also be extremely helpful. Finally, if the positive valence scale also has a long-tail, focusing one's career in developing bliss technologies may pay-off in surprisingly good ways (whereby you may stumble on methods to generate high-valence healing experiences which are orders of magnitude better than you thought were possible). Introduction Weber's Law Weber's Law describes the relationship between the physical intensity of a stimulus and the reported subjective intensity of perceiving it. For example, it describes the relationship between how loud a sound is and how loud it is perceived as. In the general case, Weber's Law indicates that one needs to vary the stimulus intensity by a multiplicative fraction (called “Weber's fraction”) in order to detect a just noticeable difference. For example, if you cannot detect the differences between objects weighing 100 grams to 105 grams, then you will also not be able to detect the differences between objects weighing 200 grams to 210 grams (implying the Weber fraction for weight perception is at least 5%). In the general case, the senses detect differences logarithmically. There are two compelling stories for interpreting this law: In the first story, it is the low-level processing of the senses which do the logarithmic mapping. The senses “compress” the intensity of the stimulation and send a “linearized” packet of information to one's brain, which is then rendered linearly in one's experience. In the second story, the senses, within the window of adaptation, do a fine job of translating (somewhat) faithfully the actual intensity of the stimulus, which then gets rendered in our experience. Our inability to detect small absolute differences between intense stimuli is not because we are not rendering such differences, but because Weber's law applies to the very intensity of experience. ...

welcome to the nonlinear library, where we use text-to-speech software to convert the best writing from the rationalist and ea communities into audio. T his is: Can my self-worth compare to my instrumental value?, published by C Tilli on the effective altruism forum. A personal reflection on how my experience of EA is similar to my experience of religious faith in that it provides a sense of purpose and belonging, but that I miss the assurance of my own intrinsic value and how that can make it difficult to maintain a stable sense of self-worth. Note: I realize that my experience of religion and faith is probably different from that of a lot of other people. My aim is not to get into a discussion of what religion does right or wrong, especially since I am no longer religious. I grew up with a close connection to my local church and was rather religious until my mid-late teenage years. I am now in my thirties and have been involved with the EA movement for a couple of years. To me, there are similarities between how I remember relating to faith and church and how I now relate to the EA philosophy and movement. For me, both provide (provided) a strong sense of purpose and belonging. There is a feeling that I matter as an individual and that I can have an important mission in life, that I can even be some kind of heroine. For both, there is also a supportive community (of course not always for everyone, but my experience has been mainly positive in both cases) that shares my values and understands and supports how this sense of mission affects many of my important life decisions. This is something that I find very valuable. However, in comparison to what my faith and church used to offer me, there is something lacking in the case of EA. I miss the assurance that I as a person have an intrinsic value, in addition to my instrumental value as a potential world-saviour. With faith, you are constantly reminded that God loves you, that God created you just as you are and that you are therefore, in a sense, flawless. There is a path for everyone, and you are always seen and loved in the most important way. This can be a very comforting message, and I feel it has a function to cushion the tough demands that come with the world-saving mission. The instrumental value you have through your mission to do good is in a way balanced by the assurance that no matter what, you also have infinite intrinsic value. With EA, I don't find any corresponding comforting thought or philosophy to rest in. If I am a well-off, capable person in the rich world, the QALYs I could create or save for others are likely to be much more than the QALYs I can live through myself. This seems to say that my value is mostly made up of my instrumental value, and that my individual wellbeing is less important compared to what I could achieve for others. I believe that if community members perceive that their value is primarily instrumental, this might damage their (our) mental well-being, specifically risking that many people might suffer burnouts. The idea that most of the impact is achieved by a few, very impactful people could also make the people who perceive themselves as having potential for high impact particularly vulnerable, since the gap between their intrinsic value or self-worth and their instrumental value would seem even wider. If the value of our work (the QALYs we can save) is orders of magnitude greater than the value of ourselves (the QALYs we can live), what does that mean? Can we justify self-care, other than as a means to improve ourselves to perform better? Is it possible then to build a stable sense of self-worth that is not contingent on performance? I have read several previous posts on EA's struggling with feelings of not achieving enough (In praise of unhistoric heroism, Doing good is as good as it ever was, Burnout and self-care), and to me this seems closely related to what I'm trying to address here. I'm not sure what can be done about this ...

welcome to the nonlinear library, where we use text-to-speech software to convert the best writing from the rationalist and ea communities into audio. This is: Health and happiness research topics—Part 1: Background on QALYs and DALYs, published by Derek on the effective altruism forum. Sequence contents Background on QALYs and DALYs The HALY+: Improving preference-based health metrics The sHALY: Developing subjective wellbeing-based health metrics The WELBY (i): Measuring states worse than dead The WELBY (ii): Establishing cardinality The WELBY (iii): Capturing spillover effects The WELBY (iv): Other measurement challenges Applications in effective altruism Applications outside effective altruism Conclusions Sequence summary Note: As many of the posts have not yet been completed, I may edit this summary to reflect the final content. This series of posts describes some of the metrics commonly used to evaluate health interventions and estimate the burden of disease, explains some problems with them, presents some alternatives, and suggests some potentially fruitful areas for further research.[1] It is primarily aimed at members of the effective altruism (EA) community who may wish to carry out one of the projects. Many of the topics would be suitable for student dissertations (especially in health economics, public health, psychology, and perhaps philosophy), but some of the most promising ideas would require major financial investment. Parts of the sequence—particularly the first and last posts—may also be worth reading for EAs with a general interest in evaluation methodology, global health, mental health, social care, and related fields. I begin by looking at health-adjusted life-years (HALYs), particularly the quality-adjusted life-year (QALY) and the disability-adjusted life-year (DALY). By combining length of life and level of health in one metric, these enable direct comparison across a wide variety of health conditions, making them popular both for evaluating healthcare programmes and for quantifying the burden of diseases, injuries, and risk factors in a population. I've also heard EAs using these concepts informally as a generic unit of value. However, HALYs have a number of major shortcomings in their current form. In particular, they: neglect non-health consequences of health interventions rely on poorly-informed judgements of the general public fail to acknowledge extreme suffering (and happiness) are difficult to interpret, capturing some but not all spillover effects are of little use in prioritising across sectors or cause areas This can lead to inefficient allocation of resources, in healthcare and beyond. Broadly, three alternative measures[2] could be developed in order to address these limitations: The HALY+: a tweaked version of the original QALY or DALY that captures some non-health outcomes and/or relies on more informed preferences. The sHALY: a “subjective wellbeing-based HALY” that retains the health-focused descriptive system but assigns weights to health states using experienced wellbeing rather than preferences. The WELBY: a wellbeing-adjusted life-year that can, in principle, capture the benefits of all kinds of intervention. A variation, the pWELBY, uses preferences to assign weights to each level of wellbeing. After introducing these metrics, this sequence of posts considers the additional research required to create them, and potential applications both within and outside EA. The importance, tractability, and neglectedness of each major project is briefly considered, though I do not attempt a formal priority ranking.[3] For individual researchers, my extremely tentative view is that work to establish the “dead point” (below which are states worse than dead) and lower bound on wellbeing scales is likely to have the greatest payoff—but, as with careers in general, the best choice of project is likely to depend heavily on personal fit. For well-funded research teams, including some large EA orga...

We use QALYs to judge how good treatments are and compare them to other treatments, but what are their limitations? Can we use the recent discussions about whether teenagers should be vaccinated against Covid to illustrate these things about QALYs? Listen to find out how successfully we've done this!

Researchers in the Effective Altruism movement often view their work through a utilitarian lens, so why haven't they traditionally paid much attention to the psychological research into subjective wellbeing (i.e., people's self-reported levels of happiness, life satisfaction, feelings of purpose and meaning in life, etc.)? Are such subjective measures reliable and accurate? Or rather, which such measures are the most reliable and accurate? What are the pros and cons of using QALYs and DALYs to quantify wellbeing? Why is there sometimes a disconnect between the projected level of subjective wellbeing of a health condition and its actual level (e.g., some people can learn to manage and cope with "major" diseases, but some people with "minor" conditions like depression or anxiety might be in a constant state of agony)? What are some new and promising approaches to quantifying wellbeing? The EA movement typically uses the criteria of scale, neglectedness, and tractability for prioritizing cause areas; is that framework still relevant and useful? How do those criteria apply on a personal level? And how do those criteria taken together differ conceptually from cost-effectiveness? How effective are psychological interventions at improving subjective wellbeing? How well do such interventions work in different cultures? How can subjective wellbeing measures be improved? How can philosophers help us do good better? Michael Plant is the Founder and Director of the Happier Lives Institute, a non-profit research institute that searches for the most cost-effective ways to increase global well-being. Michael is also a Research Fellow at the Wellbeing Research Centre, Oxford. He has a PhD in Philosophy from Oxford, and his thesis, entitled Doing Good Badly? Philosophical Issues Related to Effective Altruism, was supervised by Peter Singer and Hilary Greaves.

Read the full transcript here. Researchers in the Effective Altruism movement often view their work through a utilitarian lens, so why haven't they traditionally paid much attention to the psychological research into subjective wellbeing (i.e., people's self-reported levels of happiness, life satisfaction, feelings of purpose and meaning in life, etc.)? Are such subjective measures reliable and accurate? Or rather, which such measures are the most reliable and accurate? What are the pros and cons of using QALYs and DALYs to quantify wellbeing? Why is there sometimes a disconnect between the projected level of subjective wellbeing of a health condition and its actual level (e.g., some people can learn to manage and cope with "major" diseases, but some people with "minor" conditions like depression or anxiety might be in a constant state of agony)? What are some new and promising approaches to quantifying wellbeing? The EA movement typically uses the criteria of scale, neglectedness, and tractability for prioritizing cause areas; is that framework still relevant and useful? How do those criteria apply on a personal level? And how do those criteria taken together differ conceptually from cost-effectiveness? How effective are psychological interventions at improving subjective wellbeing? How well do such interventions work in different cultures? How can subjective wellbeing measures be improved? How can philosophers help us do good better?Michael Plant is the Founder and Director of the Happier Lives Institute, a non-profit research institute that searches for the most cost-effective ways to increase global well-being. Michael is also a Research Fellow at the Wellbeing Research Centre, Oxford. He has a PhD in Philosophy from Oxford, and his thesis, entitled Doing Good Badly? Philosophical Issues Related to Effective Altruism, was supervised by Peter Singer and Hilary Greaves. [Read more]

Read the full transcriptResearchers in the Effective Altruism movement often view their work through a utilitarian lens, so why haven't they traditionally paid much attention to the psychological research into subjective wellbeing (i.e., people's self-reported levels of happiness, life satisfaction, feelings of purpose and meaning in life, etc.)? Are such subjective measures reliable and accurate? Or rather, which such measures are the most reliable and accurate? What are the pros and cons of using QALYs and DALYs to quantify wellbeing? Why is there sometimes a disconnect between the projected level of subjective wellbeing of a health condition and its actual level (e.g., some people can learn to manage and cope with "major" diseases, but some people with "minor" conditions like depression or anxiety might be in a constant state of agony)? What are some new and promising approaches to quantifying wellbeing? The EA movement typically uses the criteria of scale, neglectedness, and tractability for prioritizing cause areas; is that framework still relevant and useful? How do those criteria apply on a personal level? And how do those criteria taken together differ conceptually from cost-effectiveness? How effective are psychological interventions at improving subjective wellbeing? How well do such interventions work in different cultures? How can subjective wellbeing measures be improved? How can philosophers help us do good better?Michael Plant is the Founder and Director of the Happier Lives Institute, a non-profit research institute that searches for the most cost-effective ways to increase global well-being. Michael is also a Research Fellow at the Wellbeing Research Centre, Oxford. He has a PhD in Philosophy from Oxford, and his thesis, entitled Doing Good Badly? Philosophical Issues Related to Effective Altruism, was supervised by Peter Singer and Hilary Greaves.

Researchers in the Effective Altruism movement often view their work through a utilitarian lens, so why haven't they traditionally paid much attention to the psychological research into subjective wellbeing (i.e., people's self-reported levels of happiness, life satisfaction, feelings of purpose and meaning in life, etc.)? Are such subjective measures reliable and accurate? Or rather, which such measures are the most reliable and accurate? What are the pros and cons of using QALYs and DALYs to quantify wellbeing? Why is there sometimes a disconnect between the projected level of subjective wellbeing of a health condition and its actual level (e.g., some people can learn to manage and cope with "major" diseases, but some people with "minor" conditions like depression or anxiety might be in a constant state of agony)? What are some new and promising approaches to quantifying wellbeing? The EA movement typically uses the criteria of scale, neglectedness, and tractability for prioritizing cause areas; is that framework still relevant and useful? How do those criteria apply on a personal level? And how do those criteria taken together differ conceptually from cost-effectiveness? How effective are psychological interventions at improving subjective wellbeing? How well do such interventions work in different cultures? How can subjective wellbeing measures be improved? How can philosophers help us do good better?Michael Plant is the Founder and Director of the Happier Lives Institute, a non-profit research institute that searches for the most cost-effective ways to increase global well-being. Michael is also a Research Fellow at the Wellbeing Research Centre, Oxford. He has a PhD in Philosophy from Oxford, and his thesis, entitled Doing Good Badly? Philosophical Issues Related to Effective Altruism, was supervised by Peter Singer and Hilary Greaves.

The quality-adjusted life-year (QALY) combines the expected effects on longevity and the expected effects on quality-of-life into a single standard measure. QALYs are often used as part of cost effectiveness analysis, particularly when analyzing the effectiveness of drugs.QALY as a measurement has received a lot of criticism. It's been criticized in concept or in the specifics of how it's defined or used. This criticism often forms the basis for opposition to price negotiations or any limitations on access to a particular drug. This kind of criticism can make it difficult to reach a consensus on processes that might yield negotiated or regulated drug prices.Leah Rand, a postdoctoral fellow at Harvard Medical School and Brigham and Women's Hospital, joins A Health Podyssey to talk about QALY, its criticism, and how to respond to that criticism.Rand and coauthor Aaron Kesselheim published in the September 2021 issue of Health Affairs a systematic literature review of critiques of QALYs and their relevance to drug health technology assessments. They identify three main categories of ethical and practical critiques of QALYS, including methodological concerns, criticisms of neutrality, and potential discrimination. Rand and Kesselheim conclude that understanding and addressing criticism of the QALY is essential for the move to value-based pricing.Listen as Health Affairs Editor-in-Chief Alan Weil interviews Leah Rand on the pros and cons of the Quality Adjusted Life Year measurement in health policy.Subscribe: RSS | Apple Podcasts | Spotify | Stitcher | Google Podcasts

A new study evaluates the cost-effectiveness of dapagliflozin in heart failure. Geoff and Jake continue the conversation from "Home Sweet Home (It's Where the Heart Is)" [Previous Episode] about the role of SGLT-2is in heart failure. This time the conversation is focused on the cost-effectiveness and QALYs. Is the price right for improved care?Redeem your CPE or CME credit here!We want your feedback! Share your feedback and experience with GameChangers! https://www.jotform.com/build/90155144694964References and resources: Parizo JT, Goldhaber-Fiebert JD, Salomon JA, et al. Cost-effectiveness of Dapagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction. JAMA Cardiol. Published online May 26, 2021. doi:10.1001/jamacardio.2021.1437Continuing Education Information:Learning Objectives: 1. Define QALY2. Discuss the cost-effectiveness of dapagliflozin in heart failure0.05 CEU | 0.5 HrsACPE UAN: 0107-0000-21-264-H01-PInitial release date: 7/20/21Expiration date: 7/20/2022Complete CPE & CME details can be found here.

The global burden of COVID-19 has predominantly been measured using metrics like case numbers, hospitalisations and deaths. But the long term health impacts are more difficult to capture. In this episode of Coronapod we discuss one way that public health experts are trying to get to grips with the problem using metrics such as disability adjusted life years (DALYs) and quality adjusted life years (QALYs).As new data suggests that COVID could leave millions with lasting disability or ill-health, we ask how changing the lens through which we asses the impacts of COVID could change public health policies, the perception of risk and even the behaviour of individuals.News Feature: The four most urgent questions about long COVIDComment: Count the cost of disability caused by COVID-19Subscribe to Nature Briefing, an unmissable daily round-up of science news, opinion and analysis free in your inbox every weekday. See acast.com/privacy for privacy and opt-out information.

In this episode, we talk with Andrés Gallegos, chairman of the National Council on Disability (NCD), about his recent commentary in Health Affairs, “Misperceptions of People with Disabilities Lead to Low-Quality Care: How Policymakers Can Counter the Harm and Injustice.” He shares insight on the impact of gaps in disability data, the underrepresentation of people with disabilities in leadership positions, disability cultural competency, and how quality-adjusted life years (QALYs) are barriers to equitable health care. Learn more about the National Council on Disability (NCD) here: https://ncd.gov/ Episode Transcript: https://documentcloud.adobe.com/link/track?uri=urn:aaid:scds:US:dd0c6a7f-ce43-42cc-ba90-744e2d55ab14  

Columnist Sarah Carey discusses the Irish wake, QALYs and Lough Crew

Rare Disease Day is February 28. New and exciting medical innovations and drug therapies for rare disease abound, but accessing those treatments is another challenge. Discriminatory healthcare metrics like quality-adjusted-life-years (QALYs) devalue rare disease patient lives, signaling that a patient’s life isn’t worth covering treatments and therapies. Dr. Bill Smith explains how QALYs are used and how it prevents patients from getting the life-saving care they need. Plus, Patients Rising Field Correspondent Kate speaks with Marni Cartelli, a rare disease patient living with complex regional pain syndrome, and Patient Correspondent Lillian Isabella celebrates Rare Disease Day by sharing her story of being diagnosed with PKU. Guest:William Smith, Ph.D. Visiting Fellow in the Life Sciences, The Pioneer InstituteDr. William S. Smith is The Pioneer Institute’s Visiting Fellow in the Life Sciences. Smith has 25 years of experience in government and in corporate roles, including senior staff positions on Capitol Hill, the White House Office of National Drug Control Policy, and the Massachusetts Governor’s office where he served under Governors Weld and Cellucci. He spent ten years at Pfizer Inc as Vice President of Public Affairs and Policy where he was responsible for Pfizer’s corporate strategies for the U.S. policy environment. He later served as a consultant to major pharmaceutical, biotechnology and medical device companies. Dr. Smith earned his Ph.D. in political science with distinction at The Catholic University of America.Links:William Smith, Ph.D.The Biden administration needs to look beyond ICER for evaluating drug therapiesInside Xavier Becerra’s quest for health care for immigrantsMaryland Senate overrides Hogan veto of bill that funds nation’s first drug affordability boardSenate Democrats push for public option as Biden weighs health-care reform plansMarni CartelliPatients Rising Concierge Patient Correspondent: Lillian IsabellaNeed help?The successful patient is one who can get what they need when they need it. We all know insurance slows us down, so why not take matters into your own hands. Our Navigator is an online tool that allows you to search a massive network of health-related resources using your zip code so you get local results. Get proactive and become a more successful patient right now at PatientsRisingConcierge.orgHave a question or comment about the show, want to suggest a show topic or share your story as a patient correspondent?Drop us a line: podcast@patientsrising.orgThe views and opinions expressed herein are those of the guest(s)/ author(s) and do not reflect the official policy or position of Patients Rising.

You know back in the olden days when a foot of measurement was actually the measure of your own foot? So, I might measure something and it’s, like, 19 feet. And then you measure the same exact thing and it’s 38 feet because you have tiny feet. This is the analogy that kept running through my mind as I was talking with Anna Kaltenboeck in this health care podcast about QALYs to measure the value of drugs. In this metaphor, QALYs are the ruler so that 1 foot of drug value is the same for everybody and all drugs. It’s very civilized as a concept if you think about it. QALY stands for quality-adjusted life year. The goal of a QALY is to figure out how much any given drug is worth to a society so that we, as a society, have a benchmark to evaluate the price of pharmaceutical products. QALYs are an apples to apples or a foot to foot way to compare the value of drugs for we the people. I mean, is this drug amazing and we should all pay a lot for it? Or is the drug more expensive than the current standard of treatment and it doesn’t confer any added benefit to patients? It’d be good to know that as a patient and as a payer and, frankly, as a pharma company. QALYs offer a framework for levelheaded discussions. It’s complicated. I’m gonna take the risk of oversimplifying, but here’s how I’d explain the three parts in a QALY measurement, which combines measure pharmaceutical value. The first part is, if relevant, how much additional survival can be expected with this drug? So, if it’s an oncology drug, for example, how much longer will the patient live? The second part of a QALY is, how does the drug make the patient feel? So, in an ideal world, survival is long and the patient feels super great. So, some economists and scientists get together and they do some math and they come up with the sum of these first two factors. Then the third part of a QALY calculation is the cold hard cash. How much is society willing to pay for this improvement in survival, in quality of life? This last part will depend based on the society (ie, the country) and also the condition. We’re willing to pay a lot for a drug that helps blind people see. We might be not so willing to pay a whole lot for a drug that lowers blood pressure marginally, for example. My guest in this health care podcast is Anna Kaltenboeck. She is a health economist and program director for the Drug Pricing Lab at Memorial Sloan Kettering. She knows a lot about QALYs. One last thing: ICER is the Institute for Clinical and Economic Review. It is an independent and nonprofit organization who creates a lot of these QALY assessments. Whether they succeed or not is something that is sometimes questioned, but the team over at ICER prides themselves in not working for Pharma and not working for payers in an effort to be as impartial as possible.   You can learn more at drugpricinglab.org.   Anna Kaltenboeck is the senior health economist and program director for the Center for Health Policy and Outcomes and the Drug Pricing Lab at Memorial Sloan Kettering Cancer Center (MSKCC). She focuses on the development and application of reimbursement methods for prescription drugs that reduce distortionary incentives in the supply chain and encourage pricing of treatments based on their value. Her work centers on developing an unbiased evidence base that characterizes the effect of federal policies on coverage and reimbursement decisions for branded specialty drugs and cell and gene therapies and identifying opportunities for policy changes that encourage affordability and access while maintaining incentives for innovation. Her current research interests include global comparisons of reimbursement policy and supply chain regulation, game theory in innovation decisions, and the effect of market concentration on pricing decisions. Ms. Kaltenboeck’s research and policy work is informed by her experience as a consultant for pharmaceutical clients. Prior to joining MSKCC, Ms. Kaltenboeck spent 10 years working for Analysis Group and IMS Consulting Group, where she conducted health economics and outcomes research and developed pricing and market access strategies for pharmaceutical and diagnostic products. She has published numerous articles in peer-reviewed journals and other press, including JAMA and Morning Consult, and speaks frequently on the topics of value-based pricing, economics of the supply chain, and reimbursement models. Ms. Kaltenboeck holds bachelor’s and master’s degrees in economics from Tufts University. 3:56 What is a QALY? 05:28 “You don’t get marks; it’s the treatment that gets the marks.” 09:13 What is willingness to pay? 10:52 “What we pay for drugs should be reflected in societal preference.” 12:29 Does Pharma fear the QALY? 15:38 “At the end of the day, the ideal here is simply to be able to quantify ‘This is what we’re going to pay for this additional benefit that we’re going to provide for patients.’” 17:09 “When you meet that price, patients should be getting access to that product.” 19:27 What are the significant advances being seen with QALYs and drug development? 21:23 “The challenge is when the price is so much higher than those benchmarks.” 22:27 How do we use the QALY as a tool? 25:56 Where does value-based pricing fall in the world of QALYs? You can learn more at drugpricinglab.org.   @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue What is a #QALY? @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue “You don’t get marks; it’s the treatment that gets the marks.” @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue What is willingness to pay? @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue “What we pay for drugs should be reflected in societal preference.” @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue Does Pharma fear the QALY? @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue “At the end of the day, the ideal here is simply to be able to quantify ‘This is what we’re going to pay for this additional benefit that we’re going to provide for patients.’” @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue “When you meet that price, patients should be getting access to that product.” @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue How do we use the QALY as a tool? @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue Where does value-based pricing fall in the world of QALYs? @a_kaltenboeck discusses #drugpricing and #patientadvocacy in this week’s #healthcarepodcast. #healthcare #podcast #digitalhealth #healthtech #healthvalue #drugvalue

A victory for patients in Oklahoma as the state bans a discriminatory healthcare metric. Quality-adjusted-life-years (QALYs) are used by numerous insurance companies to block coverage based on disability or age. Two mothers of children with spinal muscular atrophy (SMA) explain how QALYs impact their children’s access to affordable healthcare.  Guest:  Amanda Chaffin Amanda Chaffin is the mother of Kayden, a seven-year-old with spinal muscular atrophy (SMA). Amanda and her family reside in Norman, Oklahoma, where a ban on quality-adjusted-life-years was recently enacted.  Following Kayden’s diagnosis, Amanda faced immense challenges in securing the medical equipment he needed, which propelled her into the patient advocacy space. She works with Cure SMA, an organization that drives funding for SMA research and provides support for families affected by the genetic disease.  Kayden Chaffin made news headlines over the thousands of Christmas cards that strangers sent to him over the holidays.  Hosts: Terry Wilcox, Executive Director, Patients Rising Dr. Robert Goldberg, “Dr. Bob”, Co-Founder and Vice President of the Center for Medicine in the Public Interest. Kate Pecora, Field Correspondent  Links: Oklahoma QALY Ban Patients Anticipate Future Access to Care Troubles from COVID-19 Kayden’s Christmas Cards Cure SMA Patients Rising Concierge  Need help? The successful patient is one who can get what they need when they need it. We all know insurance slows us down, so why not take matters into your own hands. Our Navigator is an online tool that allows you to search a massive network of health-related resources using your zip code so you get local results. Get proactive and become a more successful patient right now at PatientsRisingConcierge.org Have a question or comment about the show, want to suggest a show topic or share your story as a patient correspondent? Drop us a line: podcast@patientsrising.org The views and opinions expressed herein are those of the guest(s)/ author(s) and do not reflect the official policy or position of Patients Rising.

Would you trade a month of your life to give a decade to a stranger?  What if it were four strangers? Or thirty?

Most of us want to help.  But it can be hard to know how to do it, and not all altruistic deeds are equal, and sometimes they can be harmful.  Sometimes glitzy charities satisfy the heart of a giver, but fail to deliver results.That’s the paradox: motivating people to give often demands glitz, but glitzy causes often don’t provide the improvement to people’s lives than their less glamorous charity counterparts.  GiveWell is a organization that quantitatively evaluates charities by the actions they accomplish.  Their current suggestions for effective charities include groups treating malaria, de-worming, and direct cash giving to the poorest people in the world.  These effective charities are able to accomplish more with less resources. GiveWell is a part of a philosophical and social movement called Effective Altruism.  EA practitioners look for ways to maximize the effect of donations or other charitable acts by quantifying the impacts of giving.  This approach has been called “robotic” and “elitist” by at least one critic. In 2014, a post showed up on effectivealtruism.org’s forum, written by Thomas Kelly and Josh Morrison.  The title sums up their argument well: Kidney donation is a reasonable choice for effective altruists and more should consider it. They lay out the case for helping others through kidney donation.  Kidney disease is a huge killer in the United States, with an estimated one in seven adults having the disease (though many are undiagnosed).  And those with failing kidneys have generally bad health outcomes, with many dying on the waitlist for an organ they never receive.  There’s currently about 100,000 people in the country on the kidney donation waitlist.  An editorial recently published in the Journal of the American Society of Nephrology estimated that 40,000 Americans die annually waiting for a kidney. The previously mentioned post on the EA forums attempts to calculate all the goods that kidney donation can do, namely adding between six and twenty good years to someone’s life.  Quantifying the “goodness” of a year is tricky, so EAs (and others) use a metric called “Quality Adjusted Life Years” or QALYs. The post also attempts to calculate the downsides to the donor, namely potential lost wages, potential surgery complications, and a bit of a decrease in total kidney function.  The post concludes that kidney donation is a “reasonable” choice.  By the EA standards, “reasonable” is pretty high praise; a month or so of suffering to give about a decade of good life to someone else, all with little long term risk to the donor.  On this episode, Jeff interviews Dylan Matthews, who donated his kidney back in 2016.  His donation was non-directed, meaning he didn’t specify a desired recipient.  This kind of donation is somewhat rare, comprising only about 3% of all kidney donations.  However, non-directed donations are incredibly useful due to the difficulty of matching donors to recipients, since most kidney donors can’t match with the people they’d like to give to. When someone needs a kidney transplant, it’s usually a family member that steps up.  However, organ matching is complicated, much moreso than simple blood-type matching.  So, long series of organ trades are arranged between donors and recipients.  It’s a very complicated math problem that economist Alvin E. Roth figured out, creating an algorithm for matching series of people together for organ transplants (and also matching students to schools and other complex problems).  This algorithm is so helpful that it won him a nobel prize.While the problem of matching donors to patients is difficult no matter what, it becomes much easier when a non-directed donor like Dylan can start a chain of donations.  Dylan started a donation chain that ultimately transferred four good kidneys to people in need.  And since Dylan’s donation was non-directed, the final recipient on his chain was someone without a family member to offer a kidney in return—someone who otherwise wouldn’t have had a chance to receive a new kidney. Dylan speaks about his kidney donation experience to break down something that he sees as a unhelpful misconception: the perception that organ donors must be somehow unusually saintly.  He argues that kidney donation is a normal way to help others, and an option that most can consider.If you’re interested in kidney donation, Dylan recommends the National Kidney Registry and Waitlist Zero. Dylan Matthews is a senior correspondent at Vox and the host of the podcast Future Perfect.  Jeff found out about Dylan from the podcast Rationally Speaking with Julia Galef. Also on this episode: Beth’s looking for help. She’s been thinking about some media she consumed as a kid that no else seems to remember or have even heard of. She’s tried Googling and checked various message boards, but hasn’t had any luck.The first is a movie (or maybe a TV show). In it, a time traveler, who is an older man, travels to the “future” (which at the time of Beth’s viewing was the mid-1990s.) The Time Traveler is stranded when his time machine breaks, but he is hopeful and friendly, and he ends up enlisting some neighborhood kids to help him find the parts he needs to repair his time machine. Eventually the kids are caught by their parents, who call the authorities. The police confiscate the time machine and take The Time Traveler into custody. As he’s being arrested, the once-jovial Time Traveler is distraught. He cries, “I want to go home, I just want to go home!” over and over.The second is a book. In this book, there’s a family of three or so kids, a mom, and a mean step-dad. The mom dies, and the kids are left with their mean step-dad. They grieve, and the step-dad gets meaner. Then there is an alien that gets into their house, possibly crawling down the chimney. The alien gets into one of the closets, and slowly starts taking over the house. The siblings find the alien in the closet and observe it. There is either a beep, or maybe a flashing light, that is beeping/flashing slowly, but gradually starts beeping/flashing more rapidly. They realize the alien doesn’t want to hurt them, it just needs to use their house to build a spaceship.  The house changes, getting stranger and stranger, and the beeping/flashing gets faster and faster. The kids realize the beep/flash is a timer, and that soon the house will blast off into outer space. Just as the house is about to take off, the siblings lock their mean step-dad in the closet, and he is whisked away in a spaceship that used to be their house.Do either of these sound familiar to you? They both made an impression on Beth, and she’d love to revisit them as an adult to see how her memory holds up.Please call, tweet, or email with any leads.  (765)374-5263, @HBMpodcast, and HBMpodcast@gmail.com respectively. Producer: Jeff EmtmanEditor: Bethany DentonMusic: The Black Spot

Most of us want to help. But it can be hard to know how to do it, and not all altruistic deeds are equal, and sometimes they can be harmful. Sometimes glitzy charities satisfy the heart of a giver, but fail to deliver results.That's the paradox: motivating people to give often demands glitz, but glitzy causes often don't provide the improvement to people's lives than their less glamorous charity counterparts. GiveWell is a organization that quantitatively evaluates charities by the actions they accomplish. Their current suggestions for effective charities include groups treating malaria, de-worming, and direct cash giving to the poorest people in the world. These effective charities are able to accomplish more with less resources. GiveWell is a part of a philosophical and social movement called Effective Altruism. EA practitioners look for ways to maximize the effect of donations or other charitable acts by quantifying the impacts of giving. This approach has been called “robotic” and “elitist” by at least one critic. In 2014, a post showed up on effectivealtruism.org's forum, written by Thomas Kelly and Josh Morrison. The title sums up their argument well: Kidney donation is a reasonable choice for effective altruists and more should consider it. They lay out the case for helping others through kidney donation. Kidney disease is a huge killer in the United States, with an estimated one in seven adults having the disease (though many are undiagnosed). And those with failing kidneys have generally bad health outcomes, with many dying on the waitlist for an organ they never receive. There's currently about 100,000 people in the country on the kidney donation waitlist. An editorial recently published in the Journal of the American Society of Nephrology estimated that 40,000 Americans die annually waiting for a kidney. The previously mentioned post on the EA forums attempts to calculate all the goods that kidney donation can do, namely adding between six and twenty good years to someone's life. Quantifying the “goodness” of a year is tricky, so EAs (and others) use a metric called “Quality Adjusted Life Years” or QALYs. The post also attempts to calculate the downsides to the donor, namely potential lost wages, potential surgery complications, and a bit of a decrease in total kidney function. The post concludes that kidney donation is a “reasonable” choice. By the EA standards, “reasonable” is pretty high praise; a month or so of suffering to give about a decade of good life to someone else, all with little long term risk to the donor. On this episode, Jeff interviews Dylan Matthews, who donated his kidney back in 2016. His donation was non-directed, meaning he didn't specify a desired recipient. This kind of donation is somewhat rare, comprising only about 3% of all kidney donations. However, non-directed donations are incredibly useful due to the difficulty of matching donors to recipients, since most kidney donors can't match with the people they'd like to give to. When someone needs a kidney transplant, it's usually a family member that steps up. However, organ matching is complicated, much moreso than simple blood-type matching. So, long series of organ trades are arranged between donors and recipients. It's a very complicated math problem that economist Alvin E. Roth figured out, creating an algorithm for matching series of people together for organ transplants (and also matching students to schools and other complex problems). This algorithm is so helpful that it won him a nobel prize.While the problem of matching donors to patients is difficult no matter what, it becomes much easier when a non-directed donor like Dylan can start a chain of donations. Dylan started a donation chain that ultimately transferred four good kidneys to people in need. And since Dylan's donation was non-directed, the final recipient on his chain was someone without a family member to offer a kidney in return—someone who otherwise wouldn't have had a chance to receive a new kidney. Dylan speaks about his kidney donation experience to break down something that he sees as a unhelpful misconception: the perception that organ donors must be somehow unusually saintly. He argues that kidney donation is a normal way to help others, and an option that most can consider.If you're interested in kidney donation, Dylan recommends the National Kidney Registry and Waitlist Zero. Dylan Matthews is a senior correspondent at Vox and the host of the podcast Future Perfect. Jeff found out about Dylan from the podcast Rationally Speaking with Julia Galef. Also on this episode: Beth's looking for help. She's been thinking about some media she consumed as a kid that no else seems to remember or have even heard of. She's tried Googling and checked various message boards, but hasn't had any luck.The first is a movie (or maybe a TV show). In it, a time traveler, who is an older man, travels to the “future” (which at the time of Beth's viewing was the mid-1990s.) The Time Traveler is stranded when his time machine breaks, but he is hopeful and friendly, and he ends up enlisting some neighborhood kids to help him find the parts he needs to repair his time machine. Eventually the kids are caught by their parents, who call the authorities. The police confiscate the time machine and take The Time Traveler into custody. As he's being arrested, the once-jovial Time Traveler is distraught. He cries, “I want to go home, I just want to go home!” over and over.The second is a book. In this book, there's a family of three or so kids, a mom, and a mean step-dad. The mom dies, and the kids are left with their mean step-dad. They grieve, and the step-dad gets meaner. Then there is an alien that gets into their house, possibly crawling down the chimney. The alien gets into one of the closets, and slowly starts taking over the house. The siblings find the alien in the closet and observe it. There is either a beep, or maybe a flashing light, that is beeping/flashing slowly, but gradually starts beeping/flashing more rapidly. They realize the alien doesn't want to hurt them, it just needs to use their house to build a spaceship. The house changes, getting stranger and stranger, and the beeping/flashing gets faster and faster. The kids realize the beep/flash is a timer, and that soon the house will blast off into outer space. Just as the house is about to take off, the siblings lock their mean step-dad in the closet, and he is whisked away in a spaceship that used to be their house.Do either of these sound familiar to you? They both made an impression on Beth, and she'd love to revisit them as an adult to see how her memory holds up.Please call, tweet, or email with any leads. (765)374-5263, @HBMpodcast, and HBMpodcast@gmail.com respectively. Producer: Jeff EmtmanEditor: Bethany DentonMusic: The Black Spot

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Dr Greg Hundley, associate editor from the Pauley Heart Center in Richmond, Virginia, from VCU Health. Dr Carolyn Lam: You know what, Greg, I may have a hoarse voice today and I'm a little bit scratchy, but my goodness, I couldn't be more excited about this issue. It's the TCT issue. Dr Greg Hundley: Well Carolyn, I cannot wait to discuss with our listeners the feature article that compares Apixaban and a P2Y12 inhibitor without Aspirin, versus regimens with Aspirin in patients with AFib who have ACS, whether managed medically or with PCI, or also those undergoing elective PCI that experience regimens that include vitamin K antagonists, aspirin, or both, but more to come later. Carolyn, should I start with my first discussion article and we grab a cup of coffee? Dr Carolyn Lam: You bet, Greg. Dr Greg Hundley: So my first article is from Seung-Jung Park from the Asan Medical Center at the University of Ulsan College of Medicine. So Carolyn, here's our first quiz question. In terms of Ticagrelor, have studies been performed in those from Asia evaluating bleeding risk? Dr Carolyn Lam: You know, I have to admit, Greg, I'm not totally familiar with the literature, but I do know that it's a very important question for us practicing in Asia. We have a perception that the bleeding risk, especially intracranial bleeding, may be higher in Asians. Dr Greg Hundley: Absolutely. Well, in this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation, and intended for invasive management, were randomly assigned to receive in a one to one ratio, Ticagrelor with a 180 milligram loading dose, and then 90 milligrams twice daily, or Clopidogrel with a 600 milligram loading dose and 75 milligrams daily thereafter, and the primary safety outcome was clinically significant bleeding, which was a composite of major bleeding or minor bleeding according to the PLATO outcomes criteria at 12 months. Dr Carolyn Lam: Oh, so what did they find? Dr Greg Hundley: Well Carolyn, at 12 months, the incidence of clinically significant bleeding was higher in the Ticagrelor group than in the Clopidogrel group. So it was 11.7% versus 5.3, and that included major bleeding and fatal bleeding. They were also higher in the Ticagrelor group. The incidents of death from cardiovascular causes, myocardial infarction or stroke, was not significantly different between the Ticagrelor group and the Clopidogrel group, although there was a strong trend toward a higher incidence in the Ticagrelor group with a P value of 0.07. So consequently, Carolyn, these results identified safety concerns regarding bleeding complications of standard dose Ticagrelor in East Asian, Korean patients with acute coronary syndromes, and therefore large adequately powered randomized trials are needed to determine the optimal antithrombotic regimen in this patient population. Dr Carolyn Lam: Very important data for our patients, as is this next paper, which really examines the cost effectiveness of transcatheter mitral valve repair versus medical therapy in patients with heart failure and secondary mitral regurgitation. Now, these are results from the COAPT trial. As a reminder, the COAPT trial demonstrated that edge-to-edge transcatheter mitral valve repair using the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life when compared with maximally tolerated guideline directed medical therapy in patients with heart failure and three to four plus secondary mitral regurgitation. In the current paper, first author Dr Baron from Lahey Hospital and Medical Center in Burlington, Massachusetts and St. Luke’s Mid America Heart Institute in Kansas City, as well as corresponding author Dr Cohen from University of Missouri, Kansas City, and their colleagues used data from the COAPT trial to perform a formal patient level economic analysis of the COAPT from the perspective of the US healthcare system, and they found that although the follow up costs were lower with the MitraClip compared with guideline directed medical therapy, and lower by more than $11,000 per patient. However, the cumulative two year costs remain higher by about $35,000 per patient with the transcatheter mitral valve repair, and this is all due to the upfront costs of the index procedure. Now when in trial survival, health, utilities, and costs were modeled over a lifetime horizon, transcatheter mitral valve repair was projected to increase life expectancy by 1.13 years, and quality adjusted life years, or QALYs, by 0.82 years at a cost of $45,648, yielding a lifetime incremental cost effectiveness ratio, or ICER, of $40,361 per life year gained, and $55,600 per QALY gained. Dr Greg Hundley: Very interesting. So how do we interpret these results for clinical practice? Dr Carolyn Lam: Ah, good question. So in order to place this in context, perhaps the most comparable case is the use of transcatheter aortic valve replacement, or TAVR. So based on the partner 1B trial, the ICER for TAVR, compared to medical therapy, was $61,889 per QALY gains. So this is very similar to what you just heard as the ICER for the transcatheter mitral valve repair. The cost effectiveness is also comparable for other commonly used treatments such as the implantable cardiac defibrillators for biventricular pacing, and was interestingly substantially more than the cost effectiveness of continuous flow LVADs, for example, and this is really discussed in a beautiful editorial by Dr Bonow, Mark, and O'Gara, and in this editorial, I think it's really important that they say the cost effectiveness projections really need to be placed in the context of continuing uncertainties regarding the interpretation of COAPT compared to that of the MITRA-FR trial, which reported no benefit of transcatheter mitral valve replacement compared to medical therapy, and so they warn that the current cost effectiveness analysis is not a carte blanche for interventional cardiologists to dramatically escalate their use of MitraClip procedure, and the data do support the thoughtful and deliberate use of this potentially life lengthening procedure in carefully selected patients and under very careful circumstances. You've got to read their editorial. Dr Greg Hundley: That sounds excellent, Carolyn. I really like that, putting that editorial that puts that data in perspective. Well, my next study really emanates from the ABSORB III trial, and it's from Dr Dean Kereiakes at the Christ Hospital Heart and Vascular Center. The manuscript addresses the long-term cardiovascular event rates among bioresorbable vascular scaffolds and drug eluting metallic stents. Dr Carolyn Lam: Greg, remind me, what were the results of the original ABSORB trial? Dr Greg Hundley: Right, Carolyn. So the ABSORB III trial demonstrated non-inferior rates of target lesion failure, cardiac death, target vessel myocardial infarction, or ischemia driven target lesion revascularization at one year with the bioresorbable vascular scaffolds compared with cobalt chromium everolimus-eluting stents, but between one year and three years, and therefore the cumulative to 3 year time point, the adverse event rates, particularly for target vessel myocardial infarction and scaffold thrombosis, were increased with this bioresorbable vascular scaffold. Dr Carolyn Lam: Ah, I see. Okay, so this current study evaluated the outcomes from three to five years beyond the implantation? Dr Greg Hundley: Exactly. So what this study did is they looked at an interval of time between three and five years out, and they found reductions in the relative hazards for the bioresorbable vascular scaffolds compared to the common coated stents, and that particularly occurred for target lesion failure, either cardiac death or target vessel MI or ischemia driven target revascularization when compared to the earlier zero to three year time period. So therefore Carolyn, the authors conclude that improved scaffold design and development techniques to mitigate that zero to three year bio resorbable vascular scaffold risk may enhance the late benefits that one sees in this three to five year time point, because of the complete bioresorption. Dr Carolyn Lam: So that's interesting Greg. Well, my next paper is kind of related. It is the first report of a randomized comparison between magnesium based bioresorbable scaffold and sirolimus-eluting stent in this clinical setting of STEMI with one year clinical and angiographic follow-up. So this study is from the Spanish group, Dr Sabaté and colleagues from the Interventional Cardiology Department and Cardiovascular Institute in Barcelona in Spain, and they found that at one year when compared to the sirolimus-eluting stent, the magnesium based bioresorbable scaffold demonstrated a higher capacity of vasal motor response to pharmacological agents, either endothelium, independent or dependent, at one year. However, the magnesium based bioresorbable scaffolds were also associated with a lower angiographic efficacy, a higher rate of target lesion revascularization, but without thrombotic safety concerns. Dr Greg Hundley: Wow, Carolyn, very interesting, and Dr Lorenz Räber and Yasushi Ueki wrote a very nice editorial on this whole topic of bioresorbable scaffolds, and they wonder about some of the unfulfilled prophecies. Great for our readers to put these two articles together. Now, how about in that mailbox, Carolyn? What have you got in there? Dr Carolyn Lam: First there's a research letter by Dr Kimura entitled Very Short Dual Antiplatelet Therapy After Drug-eluting Stent Implantation in Patients with High Bleeding Risk, and that's insights from the STOPDAPT-2 trial. There's another research letter by Dr Lopes entitled The Hospitalization Among Patients with Atrial Fibrillation and a Recent Acute Coronary Syndrome, or PCI, Treated with Apixaban or Aspirin, and that's insights from the AUGUSTUS trial. A very interesting perspective piece by Dr Rob Califf entitled The Balanced Dysfunction in the Health Care Ecosystem Harms Patients, a really, really interesting read, especially those working in the U.S. healthcare system. An ECG challenge deals with fast and slow, long and shorter. I would love to give you a clue to what it is. It's got to do with the atrial ventricular nodes, but I'll let you take a look and test yourself. There’re highlights from the TCT by Drs Giustino, Leon, and Greg Stone, and finally there's Highlights from the Circulation Family of Journals by Sara O'Brien. Dr Greg Hundley: Very nice, Carolyn. Well, I've got just a couple reviews. Richard Whitlock in a primer provides a nice historical review of anticoagulation for mechanical valves. How do we get here in anticoagulating this particular patient population? Next, Dr Mark Brzezinski from Brigham Women's Hospital in the Harvard Medical School in an on my mind piece provides very elegant figures, beautiful figures, demonstrating inadequate angiogenesis within the fibrous cap of atherosclerotic plaques, and indicates this could be a source or thought of as a contributing factor toward plaque rupture. What an issue, and I can't wait to get onto that featured discussion. Dr Carolyn Lam: For our featured discussion today, it is a super-hot topic, and a question that comes up again and again in clinical practice. What is the right antithrombotic therapy in patients with atrial fibrillation and acute coronary syndrome, not just those treated with PCI, but also in those treated medically? Well guess what? We're going to have answers right here. I'm so pleased to have with us Dr Renato Lopes, who's a corresponding author from Duke Clinical Research Institute and our associate editor, Dr Stefan James from Uppsala University in Sweden. Wow. Very, very important question here. Renato, could you just start by outlining what is the AUGUSTUS trial? Dr Renato Lopes: The AUGUSTUS trial was basically one of the four trials trying to give an answer, or help answering about the antithrombotic therapy in patients with anti fibrillation and/or NACS and/or PCI. So in other words, this combination of patients undergoing PCI who require antiplatelet therapy and also patients with AFib who requires anticoagulation therapy, and in summary, what the AUGUSTUS trial did was randomize patients to Apixaban versus VKA, or aspirin placebo in a double blind fashion, and this was a two by two factorial design. So these were basically the two questions that we wanted to answer. Is Apixaban better than VKA, and is it safe to drop aspirin from this treatment strategy? Remembering that everybody received a P2Y12 inhibitor for at least eight months. So this was basically the design of the AUGUSTUS trial, trying to answer two questions in the same study, a two by two factorial design. Dr Greg Hundley: Very, very nice. And Renato, if I could, I mean I said it in the intro, but may I make sure I got it right. This is the only trial in the field that included patients with ACS that was managed medically. So that's a very important group of patients that we still don't know what the best regimen is, is that right? Dr Renato Lopes: That is correct. The other trials, the PIONEER, the RE-DUAL PCI and the VPCI, they only included patients undergoing PCI, and when we designed the trial, we thought that it would be important to also include the whole spectrum of ACS, including not only the PCI treated patients, but also the medically managed patients. Dr Greg Hundley: Well, super. So could you tell us now what were the results? Dr Renato Lopes: So first, in terms of the breakdown, we found that the breakdown of the PCI, ACS versus elective PCI, was really nice. We had about 60% of the trial being ACS patients, and about 39%-40% elective PCI, and then within the PCI, I think that our results pretty much reflect practice in a lot of parts of the world, which was about 39% medically managed and about 61% PCI treated patients. So to begin with, I think a very nice breakdown that gives us power to look at these three separate groups: ACS medically managed, ACS PCI treated, and also elective PCI, which allows us to understand the whole spectrum of coronary disease in patients also with AFib, and in summary, what we showed for the primary endpoint, which was clinical major or relevant non-major bleeding. Let's start with the Apixaban versus VKA comparison, and we show that Apixaban was safer than VKA in all three groups, in the ACS medically managed, in the PCI treated patients, and also in the elective PCI patients. There was no significant direction for those three subgroups, although it was borderline 0.052, just showing maybe a little bit less pronounced results in the elective PCI group, but nonetheless, I would say that in general, very consistent, and in terms of Aspirin for the primary endpoint, also no difference, no interaction among those three groups. In other words, as we increase substantially the risk of bleeding about two folds in all the three groups, ACS medically managed, PCI treated patients, and elective PCI patients, with about again, two fold increase in bleeding compared to placebo. If we go to ischemic events, again, that's our hospitalization and other that are ischemic events. In terms of Apixaban versus VKA, the results were very consistent with the overall trial among these three groups, and in terms of as ACS versus placebo, the results also for the ischemic events were also similar among the three groups. So again, reassuring that the main results of the trial were very consistent, regardless how patients were managed in terms of the ACS, medically or through PCI, and also included in the elect PCI group. Dr Carolyn Lam: Thank you for explaining that so well. Stephan, I would love for you to take us under the hood. What were the editors thinking when we saw this paper, why we're highlighting it now, and what do you think are the implications? Dr Stefan James: The AUGUSTUS trial was unique in many aspects. I think Renato highlighted a few of them. As he told, there have been several similar trials without the other DOAX, factor 10A inhibitors and the dabigatran, but the AUGUSTUS trial was larger. It includes, as you mentioned previously, patients with ACS and medical management, and it also was designed as a two by two factorial design. So it actually asks two different questions and made two different randomizations, both anticoagulation with the two different agents, Warfarin versus Apixaban, but also Aspirin versus placebo, and so it's possible from this trial to understand more of the different aspects of treating patients, these complex patients with atrial fibrillation, NACS or PCI, and gave the study group and us an opportunity to better understand all these complexities. So with that, I'd like to turn to Renato and try to, with that background that I just outlaid, and you just try to make us understand what are the clinical implications of these aspects of the trial and the treatment of Apixaban and Aspirin in these patients? Dr Renato Lopes: I think we were in the area that we desperately needed randomized data, because basically until five years ago, the standard of care of treating these patients was the classic triple therapy with Aspirin, Clopidogrel, and Warfarin, and this was based on no randomized trials and all observational data, and we know how problematic this is, and this field has evolved tremendously almost year after year since the PIONEER trial, since the RE-DUAL trial, and this year, we had AUGUSTUS and ENTRUST and I think now, as Mike Gibson used to say, that we have about 2.8 million different combination of antithrombotic strategies to treat these patients because we have different anticoagulants, different anti-platelets, different doses, different durations, different types of stents, which makes it really impossible for physicians or for any guidelines to contemplate all these options. So we really needed a few trials to at least try to give a few options that are evidence based and not just based on low quality of data, and I think now, if you look at the Augustus results, and the totality of the data from all these trials, which now is about almost 11,000 patients all together, actually almost 12,000 patients all together. I think that what we know today is that yes, the initial period in hospital for some time it's important to use Aspirin. I think this is an important point to highlight, Stephan, that Aspirin still needs to be used for the acute treatment, and I would say at least for the first few initial days while patients are still in the hospital, but then by the time of discharge, which sometimes might be five days, six days, seven days, I think that now the totality of data show that it's reasonable to drop Aspirin for most patients. So based on the AUGUSTUS results, what we show is that if you're going to use anticoagulation as Apixaban at the dose that is approved for stroke preventions in atrial fibrillation, combined with a P2Y12 inhibitor without Aspirin after the initial period, you have the best outcomes in terms of lower rates of bleeding, lower rates of hospitalizations, and we don't have to pay a cost in terms of ischemic events when we actually drop Aspirin and keep only the NOAC, in this case was Apixaban, plus a P2Y12 inhibitor, which most of the time was Clopidogrel, and here with AUGUSTUS, we basically show that this is true for patients with AFib and ACS, irrespective of the management with medical managing, with medical therapy, or with PCI. So I think that's an additional piece that that is true irrespective of how we're going to treat your ACS patient, or if the patient basically underwent elective PCI, and I think we learned today that the classic treatment therapy of VKA plus Aspirin plus P2Y12 inhibitor, so in other words, the triple classic triple therapy should generally be avoided. Dr Stefan James: Thank you Renato. I think that that was a very complete answer in this complex arena. I'd like just to mention that of course the AUGUSTUS, as well as the other trials, have their limitations, as all trials. Although it was large, it was powered for safety, for bleeding events, and it was not powered for ischemic events. Having said that, we still want to look at ischemic events and clinical outcomes, and to what degree do you think we can do that? What conclusions can we draw from an ischemic point of view because of the fact that the trial was underpowered for that interpretation? Dr Renato Lopes: That is a great question, Stephan, and in fact, if we look at events like stent thrombosis, they are very rare, and if you really want to attack a significant difference between Aspirin versus placebo in patients having stent thrombosis, we're really going to need a trial with about 30-40,000 people, which would be not feasible and not doable. So we need to be cautious when we analyze those events in the power trial for ischemic events. Nonetheless, there was a signal, if you look at all trials, and even in the meta-analysis that we published recently, that dropping Aspirin probably increased the risk of ischemic events, not in a statistically significant fashion, but nonetheless, this trend exists. The signal exists. So probably keeping Aspirin, add some protection for ischemic events, primarily stent thrombosis and myocardial infarction. The problem is a tradeoff. The problem is that the cost of adding aspirin is too high. So now the question to us, Stephan, is to look further into our data and in the combined data sets that we're trying to work with the other authors and try to identify, okay, Aspirin really increased the risk of bleeding, but is there a group of patients who might benefit from a little bit longer Aspirin? So that's the first question. Who are those patients? May be complex PCI, maybe bifurcation lesions, maybe multiple lesions, multiple stents, and second, if we decide to give Aspirin longer, how much longer should we give? Because again, the cost is very high in terms of bad bleeds. So we are trying now to identify what is the trade off, and who most benefit from keeping Aspirin longer, and for how long in a way the cost might be worth it to pay in exchange of potentially save some ischemic events? And with that, we can further refine the treatment that I think I highlighted before. For most patients, I think what I said before is probably reasonable. We can drop Aspirin by the time of discharge after a few days, but for a few patients, for some patients, it might be wise to keep Aspirin a little bit longer, and we are trying now to identify first, who those patients are and second, form how much longer should we keep Aspirin, since the 40,000 patient trial is very unlikely to happen. Dr Stefan James: I like his interpretation, Renato, although I wanted to highlight that there are limitations, I think this trial is extremely informant for clinicians. We learned a lot how to treat these very complex patients with complex treatments. Dr Carolyn Lam: No, I couldn't have agreed more. I mean quoting Mike Gibson, 2.8 million combinations. Well, at least we've talked about some of them here and had a very clear take home message, although with the caveats that we were discussing. Thank you so much, Stefan and Renato. This was really a great discussion, and thank you audience for joining us today. You've been listening to Circulation on the Run. Don't forget to tune in again next week. This program is copyright American Heart Association 2019.  

In this episode, Dan and Kristin are joined by Professor Andrew Wilson, chair of the Pharmaceutical Benefits Advisory Committee. We discuss: What the PBAC does How it makes decisions on which drugs to recommend for subsidy How decisions are made in difficult situations, for example with new drugs with very little long term information, or where prices are exceptionally high The PBAC is an independent expert body appointed by the Australian Government. Members include doctors, health professionals, health economists and consumer representatives. You can find out more about the work of the PBAC here If you are interested in learning more about QALY’s, Alwyn Smith’s 1987 article “Qualms about QALYs” is an interesting place to start.

Paper of the Week 7th March 2019:Future Directions in Valuing Benefits for Estimating QALYs: Is Time Up for the EQ-5D? Brazier J. E. et al (2019 http://eprints.whiterose.ac.uk/140092/11/1-s2.0-S1098301518363149-main.pdf More information can be found at www.3vh.org

Dr Goldstein speaks with ecancer at ASCO 2016 about his research into global drug pricing, with specific focus on the cost-effectiveness of bevacizumab. In the United States, the addition of bevacizumab to 1st-line chemotherapy in metastatic colorectal cancer provides an additional 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,240/QALY. With this as a comparative value, he sets out the international variation of treatment cost, and discusses the potential drivers of economic fluctuations. Addressing the wider variability of drug pricing between countries, he examines the relation between drug availability and GDP.

Background: To facilitate the discussion on the increasing number of total hip replacements (THR) and their effectiveness, we apply a joint evaluation of hospital case costs and health outcomes at the patient level to enable comparative effectiveness research (CER) based on the preoperative health state. Methods: In 2012, 292 patients from a German orthopedic hospital participated in health state evaluation before and 6 months after THR, where health-related quality of life (HRQoL) and disease specific pain and dysfunction were analyzed using EQ-5D and WOMAC scores. Costs were measured with a patient-based DRG costing scheme in a prospective observation of a cohort. Costs per quality-adjusted life year (QALY) were calculated based on the preoperative WOMAC score, as preoperative health states were found to be the best predictors of QALY gains in multivariate linear regressions. Results: Mean inpatient costs of THR were 6,310 Euros for primary replacement and 7,730 Euros for inpatient lifetime costs including revisions. QALYs gained using the U.K. population preference-weighted index were 5.95. Lifetime costs per QALY were 1,300 Euros. Conclusions: The WOMAC score and the EQ-5D score before operation were the most important predictors of QALY gains. The poorer the WOMAC score or the EQ-5D score before operation, the higher the patient benefit. Costs per QALY were far below common thresholds in all preoperative utility score groups and with all underlying calculation methodologies.

Background: There is an on-going debate about whether to perform surgery on early stage localised prostate cancer and risk the common long term side effects such as urinary incontinence and erectile dysfunction. Alternatively these patients could be closely monitored and treated only in case of disease progression (active surveillance). The aim of this paper is to develop a decision-analytic model comparing the cost-utility of active surveillance (AS) and radical prostatectomy (PE) for a cohort of 65 year old men with newly diagnosed low risk prostate cancer. Methods: A Markov model comparing PE and AS over a lifetime horizon was programmed in TreeAge from a German societal perspective. Comparative disease specific mortality was obtained from the Scandinavian Prostate Cancer Group trial. Direct costs were identified via national treatment guidelines and expert interviews covering in-patient, out-patient, medication, aids and remedies as well as out of pocket payments. Utility values were used as factor weights for age specific quality of life values of the German population. Uncertainty was assessed deterministically and probabilistically. Results: With quality adjustment, AS was the dominant strategy compared with initial treatment. In the base case, it was associated with an additional 0.04 quality adjusted life years (7.60 QALYs vs. 7.56 QALYs) and a cost reduction of (sic)6,883 per patient (2011 prices). Considering only life-years gained, PE was more effective with an incremental cost-effectiveness ratio of (sic)96,420/life year gained. Sensitivity analysis showed that the probability of developing metastases under AS and utility weights under AS are a major sources of uncertainty. A Monte Carlo simulation revealed that AS was more likely to be cost-effective even under very high willingness to pay thresholds. Conclusion: AS is likely to be a cost-saving treatment strategy for some patients with early stage localised prostate cancer. However, cost-effectiveness is dependent on patients' valuation of health states. Better predictability of tumour progression and modified reimbursement practice would support widespread use of AS in the context of the German health care system. More research is necessary in order to reliably quantify the health benefits compared with initial treatment and account for patient preferences.

Background: Economic evaluation of newborn screening poses specific methodological challenges. Amongst others, these challenges refer to the use of quality adjusted life years (QALYs) in newborns, and which costs and outcomes need to be considered in a full evaluation of newborn screening programmes. Because of the increasing scale and scope of such programmes, a better understanding of the methods of high-quality economic evaluations may be crucial for both producers/authors and consumers/reviewers of newborn screening-related economic evaluations. The aim of this study was therefore to develop specific guidelines designed to assess and improve the methodological quality of economic evaluations in newborn screening. Methods: To develop the guidelines, existing guidelines for assessing the quality of economic evaluations were identified through a literature search, and were reviewed and consolidated using a deductive iterative approach. In a subsequent test phase, these guidelines were applied to various economic evaluations which acted as case studies. Results: The guidelines for assessing and improving the methodological quality of economic evaluations in newborn screening are organized into 11 categories: "bibliographic details"

In einer retrospektiven Studie wurde bei 65 Patienten mit nicht-kleinzelligem Bronchialkarzinom, die sich 1998 in den Asklepios Fachkliniken München-Gauting einer operativen Therapie unterzogen, die Kosten für den stationären Aufenthalt ermittelt. Ziel der Arbeit war es, die tatsächlichen Kosten der chirurgischen Behandlung und deren Verteilung auf die verschiedenen Abteilungen so genau wie möglich zu ermitteln. Dabei sollte die postoperative Lebensqualität Berücksichtigung finden. Die Behandlung dieser Patienten verursachte im klinischen Bereich Kosten von 7169,93 € mit einer durchschnittlichen Behandlungsdauer von 23,11 Tagen. Mit 38 % der Gesamtkosten verbrauchte die Operationsabteilung die meisten Ressourcen, gefolgt von der Normalstation präoperativ mit 32 %, der Intensivstation mit 19 % und der Normalstation postoperativ mit 11 %. Personalkosten (47,17 %), Materialkosten (12,76 %) und Untersuchungen der Pathologie (12,27 %) wurden als größte Einzelposten identifiziert. Medikamente (1,34 %), Blutprodukte (0,23 %) und Antibiotika (0,21 %) spielten mit einem Anteil von unter 2 % der Gesamtkosten eine geringfügige Rolle. Im Vergleich zwischen Patienten der verschiedenen Tumorstadien der UICC 1997 sowie Patienten verschiedener Altersgruppen zeigten sich bezüglich der Kosten keine signifikanten Unterschiede. Bei der Analyse verschiedener Resektionsverfahren zeigten sich erweiterte Resektionen (N = 22) mit mittleren Gesamtkosten von 8366,64 € am kostenintensivsten. Dies lag an einer prolongierten Verweildauer von durchschnittlich 28,18 Tagen, kostenintensiverer Diagnostik, sowie längeren Operationszeiten (212,50 Minuten) mit erhöhten Materialkosten von 819,52 €. Die erbrachten Dienstleistungen wurden ohne Berücksichtigung der „Overheadkosten“ von den Versicherungsträgern vergütet. Unter näherungsweiser Berücksichtigung der „Overheadkosten“ wäre der Klinik ein durchschnittlicher Verlust von 1261,92 € entstanden. Gleiches hätte sich bei Patienten, die sich einem „einfachen“ Resektionsverfahren oder einem Resektionsverfahren nach Sonderentgeltklassifikation (SE) 8.03 unterzogen, bei derzeitig geltendem Vergütungssystem nach DRGs gezeigt. Die Verluste wären jedoch mit 368,40 € deutlich geringer ausgefallen. Bei Patienten, die sich anderen „erweiterten“ Resektionsverfahren (SE 8.04, 8.05 und 8.07) unterzogen, hätte die Klinik im Mittel Gewinne von 2420,44 € erwirtschaftet. Es ist jedoch hervorzuheben, dass es sich hierbei um einen Vergleich zwischen Kosten des Jahres 1998 und Erlösen des Jahres 2005 handelt, der nur beschränkt interpretierbar sein dürfte. Die ein Jahr postoperativ ermittelte Lebensqualität war im Vergleich zur altersentsprechenden Normalpopulation oder zu Patienten mit chronischen Erkrankungen deutlich schlechter. Hierbei wurde von den meisten Patienten die physische Subskala des SF-36 schlechter beurteilt, was auf eine stärkere Beeinträchtigung des köperlichen Befindens schließen läßt. Im Durchschnitt lag die postoperative Lebenserwartung bei 7,18 Jahren. Patienten in höheren Tumorstadien hatten mit 3,4 Jahren (Stadium III a) oder 1,67 Jahren (Stadium III b) jedoch eine deutlich kürzere Lebenserwartung. Der SF-36-Single-Index lag mit einem Wert von 0,64 zwischen den Indizes von Patienten mit schwerer Angina pectoris (0,5) und Herzinsuffizienz NYHA Grad III/IV (0,7), was die Schwere der Erkrankung verdeutlicht. Im Mittel wurden mit der Behandlung 4,62 qualitätsadjustierte Lebensjahre (QALYs) erzielt. Die Mittel, die zum Erreichen eines QALYs aufgewendet werden mussten („cost per QALY“), lagen durchschnittlich bei 1970,33 €. Bei den erweiterten Resektionen oder Patienten höherer Tumorstadien lagen die „costs per QALY“ mit 3192,99 € (erweiterte Resektion) und 7075,89 € (Stadium III b) wegen der kürzeren Lebenserwartung und bei den erweiterten Resektionen zusätzlich auch signifikant höheren Kosten deutlich höher. Im Vergleich mit anderen gängigen operativen Therapien (wie z. B. Hüftendoprothese mit 1813,55 - 4360,30 €/QALY) jedoch liegen die durchschnittlichen „costs per QALY“ im mittleren Bereich, sodass die operative Therapie des Bronchialkarzinoms als kosteneffektiv zu beurteilen ist. Zwischen den verschiedenen Stadien der UICC zeigten sich sowohl bezüglich der Kosten als auch bezüglich der postoperativen Lebensqualität keine signifikanten Unterschiede, was aus medizinischer und ökonomischer Sicht die operative Therapie bis in hohe Tumorstadien unter kurativer Zielsetzung rechtfertigt.