Riding in Cars with Researchers

What reasons can cause a trial to unexpectedly go away? What happens when it does? In today's episode of Riding In Cars with Researchers, Jeff Kingsley outlines some scenarios that would cause trials to suddenly close or never reach start-up despite preparation, and gives some practical suggestions for how #clinicaltrial sites can prepare for this in the future. 

What is appropriate clinical trial site budgeting? How can sites go about improving their budget negotiations? Today, Dr. Jeff Kingsley outlines the steps to take in order for your site to budget for trials successfully. A full transcript of this podcast can be found on our blog:https://iacthealth.com/riding-in-cars-with-researchers/ Follow Us On: Instagram: https://www.instagram.com/centricityusa/ Facebook: https://www.facebook.com/centricityusa Twitter: https://twitter.com/CentricityCR LinkedIn: https://www.linkedin.com/company/centricityresearch/  Contact Us:  Messenger: m.me/CentricityUSA  Phone: 888-737-7408 

What is the right size of a clinical research site? Small or large? Today, Dr. Jeff Kingsley gives insight into why he believes one site size prevails over the other.A full transcript of this podcast can be found on our blog: https://iacthealth.com/riding-in-cars-with-researchers/ Follow Us On:  Instagram: https://www.instagram.com/centricityusa/ Facebook: https://www.facebook.com/centricityusa Twitter: https://twitter.com/CentricityCR LinkedIn: https://www.linkedin.com/company/centricityresearch/  Contact Us:  Messenger: m.me/CentricityUSA  Phone: 888-737-7408 

How do you choose which research trials you should or should not be conducting as a research site?  Dr. Kingsley speaks to sites, business development professionals, and other key decision makers about the 3 things you should consider: the greater good, business development, and business in general.

When considering a trial for your site to conduct, you have to assess both people and site capacity.  If you are not measuring your site's capacity, it will affect your site's performance and may lead to failures.  Find out more in this week's edition of Riding in Cars with Researchers.

Let's talk about the differences in the use of pandemic, endemic, and epidemic and how we use them.  Is COVID-19 considered a pandemic?  Find out in this week's episode of Riding in Cars with Researchers.

In an interview with Dr. Joseph Surber, Chief Medical Officer at IACT Health, Dr. Jeff Kingsley gets to the heart of the importance of both physicians and patients participating in clinical research trials.  For physicians, isn't that why you got into the medical field - to make medicine and the lives of your patients better?  For patients, participating in clinical research trials gives you an option to participate in a modality that you would otherwise not have access to as well as it being free!  Learn more about the benefits of clinical trial participation for both physicians and patients! 

Do you know where to spend your marketing dollars in Clinical Research? How do you decide what areas to focus on? What percentage of your budget should go to what medium? How to implement your strategy?In this special edition of Riding in Cars with Researchers, Dr. Jeff Kingsley has a conversation with Dr. Christine Senn, Chief Strategist of Research Designed and COO of IACT Health, where they discuss ways to improve your existing marketing, tips to help attract patients, and how to maximize your marketing impact.

The use of technology in research is potentially of immense benefit.  Research requires a ton of attention to detail and it is easy to make a mistake when you are using paper or paper source documents like eSource.  The use of smart technology would make that easier and enhance data integrity.  Look into different technology and test them:  plan, do, act, and study!  Did it work?  Technology will revolutionize research and enhance the quality coming out of clinical research sites.  

There has been a movement going on for 28 years now to move research into the patient's home making it easier for patients to participate in research. The hardest thing we do is find patients who can meet the stringent criteria for research, and who have the time and the willingness to participate. If it's the hardest thing we do, we need to remove as many barriers as possible, and make it as easy as possible for patients to be able to participate. The direct-to-patient movement is aimed at that.  

Dr. Kingsley interviews Dr. Christine Senn, Project Manager Extraordinaire, on the benefits of using project management in clinical research. She discusses the importance of certifications and how it will help you site manage your trials more efficiently. For those interested in learning more she recommends reading Lean Six Sigma for Service by Michael L. George, and Execution: The Discipline of Getting Things Done by Larry Bossidy and Ram Charan. For more information on certification please visit ACRPNET.org.

The Japanese government just announced that they will be releasing a guidance document sometime around April of 2021, regarding how you would be able to submit data for regulatory approval there while using what's called real-world evidence in place of a placebo arm. So let's discuss this concept and what this means ethically and how it would work. It's a leap of faith for the industry to start thinking, “could we do this?”. But something that I always say is just because something's hard, doesn't mean you shouldn't do it. You should do it because it's the right thing to do. If we have enough real-world evidence data that we could leverage to eliminate placebo arms, no matter how hard it is, we should do this. We should take on that challenge.

We have a supply and demand problem. We have more people that need vaccines than we have vaccine available. It will take Pfizer and Moderna time to continue to manufacture vaccines and ramp up manufacturing a vaccine. But every time a new company gets an emergency use authorization, you're effectively instantaneously adding manufacturing facilities around the planet. Pfizer can only manufacture at this rate. Moderna can manufacture at this rate. You add another company you immediately stair-step the amount of vaccine available to the planet. And, instantaneously, you've made a difference in rapidly being able to vaccinate more people, which is how we save lives. It's also how we reopen economies and get out of the mess that we're in. So I would say to you that the reason you should still consider a COVID vaccine trial, despite the fact that there are EU approved vaccines, is because of altruism - because it helps all of humanity, you'll get fantastic healthcare, and you'll also be paid for your participation.

We're in a situation today where we've got ethical challenges pulling in opposite directions, and that's what's creating difficulty for Sponsors today. We have an immense need to do more COVID-19 vaccine research, and we already have several that are FDA emergency use authorization approved in the US and others internationally. And so now you have a situation where patients are in research trials, they've given of themselves to be in a research trial. Depending upon if they are healthcare workers or frontline workers, you're in a situation where they could get the vaccine outside of the research trial.Do you un-blind that patient? Meaning do we find out if the patient got the vaccine or the placebo in the research trial, or not? Here are the ethical challenges. If I look at an individual patient who is 75 years old and has type two diabetes and she entered a research trial, and now she can qualify to get a known vaccine outside of a research trial from the health department. If I look at an individual patient ethically, what should I do for her - unblind her? If she got the vaccine, you're cool. If she got a placebo, she needs to get a vaccine at the health department. Now let's look at all the patients that are in the research trial at the same time. If we say to all the patients, “we’ll unblind all of you so that you can get the vaccine”, we now create a situation where the trial is designed to fail because the blinding had a purpose in the first place. And if we now make a decision that makes the trial fail, that's unethical to the people that gave them of themselves to be in the trial in the first place, because they entered a trial based upon the assumption that it's going to produce a scientifically worthwhile result. And if we do something that violates that, well, that was unethical to the people that volunteered in the first place.

The majority of the COVID-19 virus that's around the world originated in Europe, not within China. There was a mutation that happened in Europe that gave that virus an advantage over the virus that came out of China. And now the majority of the virus that's around the planet is that variant that came out of Europe. And right now there's a new variant, a mutation that perhaps originated in London that we're now discussing actively. What happened in London was that the epidemiologists could see that there was a community that had more transmission of COVID-19 than the other communities. And they were questioning why - was it a cultural thing? Was that community not doing social distancing? Were they not using masks? Was there a super spread or event? Was there a big party or event that happened in that community? And they couldn't find anything. And then they look looked at the genetic profile of the virus in that community. And that's how they uncovered that there's a mutation. There's a virus floating around in that community that's now a little bit different. And now that virus is starting to travel around the world. It's now in the US. That will never stop. Mutation will always happen. Don't worry about that. Nothing we can do about that, that will happen. Not a big deal. The mutation is most likely not going to have any impact on the efficacy of our vaccines, just in terms of probabilities that mutation most likely will have nothing to do with the efficacy of our vaccines. And the other virus is going to continue to travel around the world. And we don't know which one is going to become the predominant strain. So keep getting the vaccine - don't stop vaccinate yourself.

Pfizer and BioNTech have just gotten a FDA EUA (Emergency Use Authorization). They also got EUA in England, and I believe in Canada at this point in time. We're expecting Moderna to get its’ EUA shortly, and there will be more to come. What I don't want to see is people thinking that that's it, that's the end, that there's no more need to enroll in COVID vaccine research trials. Now, why would I argue that there is still a need?

The traditional way vaccines are made is time-consuming. Traditional vaccines are grown, and because they're grown, they're difficult to make. They take time to make and it's a lengthier, costlier process. This messenger RNA (mRNA) technology is completely different and it's showing tremendous promise right now with the COVID-19 successes that we're having. Find out how!

Dr. Kingsley discusses the announcement made last week regarding AstraZeneca and Oxford University's COVID-19 vaccine candidate. What does the data set tell us? The bar for the vaccine candidates was set at 50% - meaning if you have a greater than a 50% efficacy, the FDA would consider approving your vaccine. Did AstraZeneca reach that bar?

Pfizer just released their interim analysis showing that their vaccine is 90% effective against COVID-19! The interim analysis shows a 90% efficacy - this means the vaccine protected the patients who got COVID-19 to the tune of 90% - 9 out of 10 patients who got the vaccine were immune to contracting COVID-19. Not only did they have antibodies, but they literally didn't get it at the same rate as the people who didn't get Pfizer's vaccine candidate. That's huge!

You've heard me talk in the past about the ethical and scientific imperative to have diverse patient populations in clinical research. It is unethical and scientifically unsound to do research on white men and assume that the data is going to be the same in women or people of African descent or Asian descent or any other descent. There is an ethical and scientific imperative to have diverse patient populations. Well, in the era of COVID-19, the FDA said, “Hey industry, COVID-19 is affecting minority populations more than other populations. It is impacting the African-American or black community more than it is the white community. It is impacting the Hispanic, Latino community more than it is the white community. You absolutely must have diverse patient populations in order to seek FDA approval.”

NASH is a disease without a therapy. It's a situation where there's an inflammatory response in your liver. Type 2 diabetes and obesity are our large contributors to this, and sometimes you can have obesity and Type 2 diabetes and you'll never develop liver disease. And sometimes, all of a sudden, you will develop an inflammatory response that will cause scar tissue formation in your liver and that can lead to liver failure. That's kind of what NASH is and there's no therapy. And because there's no therapy, doctors under-diagnosed, because what's the point in diagnosing you?

Herd immunity doesn’t work with the flu, nor the common cold. Dr. Kingsley discusses this and the scientific and ethical factors that go against the concept of herd immunity in this week’s episode.

The fact that these trials got put on hold should be evidence to you that these companies are maintaining their ethics. It should be evidence to you that they are not putting profit ahead of patient safety. These trials cost billions of dollars. Putting a trial on a pause costs these companies a tremendous amount of money, which is evidence that they're doing the right thing.

Bottom line….you won’t know if you have COVID-19 or the flu. There is such a tremendous overlap, even in the core symptoms of flu and COVID that telling the difference by symptomatology would be rough. And then frankly, COVID presents in people differently; even people in the same family with remarkably different symptoms. And so what that means is we're going to have to test you for both all season long, because we won't be able to tell the difference by symptoms alone.

Let's talk about FDA's emergency use authorization. Hello, I'm Dr. Jeff Kingsley and welcome to another edition of Riding in Cars with Researchers. The FDA has the ability to get products to market faster in emergency situations. It’s called the emergency use authorization, or EUA.Normally research takes 7-10 years in human clinical trials before you would ever get FDA approval. In an era of a pandemic, this is being accelerated like I've never seen before. Sponsors are conducting what is called adaptive trial designs, where they're blending different phases of research. They are still following the normal safety protocols that we would - it's still a gated approach. But it enables faster turnaround times and faster collection of data.

Hello, I'm Dr. Jeff Kingsley and welcome to another edition of Riding in Cars with Researchers. Let's talk about vaccine research! Traditional VaccinesThe vaccines that you and I have both received since childhood are derived from actual viruses or bacteria; they're derived from the actual thing that infects people. And they come in two basic forms. One is a little bit safer than the other, but they're both effective. Right now we are exploring an entirely new realm of vaccine research that is incredibly exciting, where we are in an era of genetics, the actual genetic code that could tell your body to make a very specific antibody to a very specific protein without you ever experiencing any exposure to the actual virus or bacteria. So in COVID-19 research right now, we are doing that. How does DNA Play a Part?We all remember learning about DNA in school - it's our genetic code. And we also have RNA in our bodies. RNA reads the DNA, and then it shuttles it to the machinery in your body that can generate antibodies. The vaccine research we're doing today is using messenger RNA. We are taking snippets of SARS-CoV-2, the virus that causes COVID-19, and we're taking very specific snippets of the genetic code for the spike protein so that your body will make antibodies not to the whole virus, not to random pieces of the virus, but very specifically to the piece that it uses to infect you. And so in doing so, your body, in getting the vaccine, is never exposed to the entire virus. You're never exposed to the whole thing! Fascinating area of research and super exciting! I love the research we're doing right now, including the vaccine research we're doing right now.

I'm Dr. Jeff Kingsley and welcome to another edition of Riding in Cars with Researchers. Do you want to know how we're coming up with therapies and vaccines for treating COVID-19 with therapies?We are literally looking at patients who actually survived COVID-19. And their body made the right antibodies and got rid of it. They defeated it and beat the virus. So what scientists are doing is they're taking blood samples from patients who succeeded in defeating COVID-19, and they're looking at all of the antibodies. Anytime your body sees something that is “not you” (a bacteria is not you; a virus is not you). Your body is continuously looking for threats; things that are not you. When your body sees something that it says, “Hey, this shouldn't be here; this is not me”, your body then randomly starts making antibodies to it. Most of the antibodies you make are worthless. Your body makes an antibody to a protein on a cell surface that does nothing. That antibody successfully grabs a protein, but it doesn't make a difference because that protein wasn't actually meaningful, that protein didn't have any influence in that virus's ability to infect you. So that antibody was a waste of your time. And then as you continue to be sick, your body stumbles upon an antibody that effectively defeats the virus, it hits the right protein. So what we've done is look at patients who successfully beat the virus, looked at all of their antibodies, tested all of their antibodies against the virus, and found out which antibodies actually made a difference. And then once we're able to see one that one works, found the antibody that was really successful into feeding the virus, we can then turn that into a treatment for you. That's how we're figuring out rapidly how to defeat this virus and then cr

I'm Dr. Jeff Kingsley and welcome to another edition of Riding in Cars with Researchers. Let's discuss the difference between the treatment trials for COVID-19 and the vaccine trials for COVID-19 19. The treatment trials we're doing for COVID-19 are with monoclonal antibodies. So what we're doing is we're taking known antibodies that can bind the right receptor, bind the right protein, and give you protection from COVID-19. And we're giving you the antibody! If you've gotten infected with COVID-19, your body has not yet figured out how to defeat it. We can jumpstart you by giving you an antibody that is designed to be effective in defeating COVID-19. It's different in vaccine research where we're giving your body a chance to build its own immunity, build its own antibodies, in advance of you ever getting COVID-19. So if you get COVID-19, we're trying to give you an antibody in advance of your own body's ability to figure it out and say, “Hey, let's help you out here.” And in vaccine research, we're trying to get your body to develop that very same antibody, the right antibody in advance of you having ever randomly come in contact with COVID-19 in your community, your workplace, your household. So that if you do come in contact with it, you've already got the antibodies and the virus can't infect you because of that. That's the similarity and the slight difference between our treatment of research and our vaccine research.

Hello! I'm Dr. Jeff Kingsley and welcome to another edition of Riding in Cars with Researchers in the midst of a COVID-19 pandemic. I've stopped doing lots of videos because frankly, I haven't been riding in cars, but it's time. I'm actually heading into the office right now to see some COVID-19 patients. We are treating COVID-19 positive patients. We are diagnosing patients. We are trying to prevent family members from being able to get COVID-19 from other family members in the same household who are COVID-19 positive. And we are doing vaccine trials. It's insane, but this is what you do in a pandemic. This is why we do research!What most companies call a mission statement is what I call a passionate cause. Our company's passionate cause is revolutionizing research and changing lives. And in a pandemic, how do you revolutionize research and change lives? Well, you lease extra real estate, you hire as many people as you can, and you begin becoming a force to reckon within the community and in the industry. We are doing free COVID-19 testing for everyone, all commerce, in the community. And we are doing diagnostic testing trials to find better tests for diagnosing patients with COVID. We're doing antibody and antigen tests. We're doing treatment trials, prophylaxis trials, and vaccine trials. That's how you revolutionize research. This is a therapeutic area that didn't exist eight months ago and the world needs desperately needs this research. Hence, that's what we're doing. We have leased more real estate, we have rearranged our largest office by literally moving people to different floors, rearranged rooms and storage to keep our healthy patients separated from our COVID-19 positive patients and to facilitate excellence in research. We're adding technology, adding all sorts of resources. That's how you revolutionize research.

It's important for you to think proactively when it comes to patient management. There can be issues when re-subscribing prescriptions to patients who went off of those medications for the clinical trial. Coordinating with insurance companies and pharmacies ahead of time can help with a seamless transition. 99% of patients have no issue whatsoever when finishing a research trial, but if you can do a little something extra to protect the one percent, isn't it worthwhile?

Dr. Kingsley talks to physicians about assessing the patient instead of individual data points. He encourages you in your research trials, think the same way you do in your medical practice. Individual data points are far less significant than constellations of data points. Doing so will refine your quality. Doing so will ensure that your adverse event list is higher quality than if you don’t. The patients you put in research trials will be higher quality patients. The patients that you screen fail or early terminate will have screen failed or early terminated for the right reasons, not the wrong reasons.

Treat the patient, not the data point. If you do this, you will have better quality data in your research trials. You will have better quality adverse event profiles. The adverse events that you document on your patients will be far more likely to be truthful and accurate than if you do otherwise. The patients that you do early terminate, or patients that you screen fail, will be far more appropriate to have been early terminated in a trial or to screen fail. We need to treat these data points differently in research than we do today. We need to treat them more like we do in normal healthcare.

Today we're going to talk about fair market value. We're going to talk about what it is and why you should care. Specifically, I'm going to try and convince you that it's flawed in how we're assessing what fair market value is in clinical research and why that matters, why it hurts. The definition of fair market value is different in the rest of the world versus in healthcare and research. Fair market value is whatever someone's willing to pay for a company: in the technology space, in private equity, in venture capital. Why should you care?

Today we are talking to patients about the level of training of the research staff seeing you in a research trial. I have a dirty little secret to share with you. There are a lot of undertrained people in the research industry. A lot. There are a lot of research coordinators that have not had adequate training and support when they get into research. There are research coordinators who’ve been in research for years, but if you test them, they cannot pass a test on their research knowledge. Meaning they haven’t learned all that much. And the same is true in physicians. There are physicians that are very competent physicians, have little to no research experience, but are given the ability to be Investigators in research trials. That is a dirty little secret in our industry. And that is something we need to stop; something we need to fight against.

As an industry, we need to recognize that cognitive overload is real and if we want a better output, we need to work hard to decrease the inputs - to simplify what we're doing as an industry. Not to simplify for simplification sake. Not to simplify to make an Investigator's life easier. To simplify because ultimately, we all win.

The FDA is not the bad guy. Just like IRB, their job is to ensure the integrity of the trial and patient safety. Find out why Dr. Kingsley thinks an audit by the FDA is not to be feared, but something that will help you ensure you are producing high quality work.

We need to improve diversity in clinical research trials. What we're going to talk about today is (1) what diversity is and (2) we'll talk about three strategies that you can implement to help improve diversity in clinical research trials.

We need to talk about the fact that physicians and patients aren't communicating. That's a problem and it's impacting clinical research. Find out how the biases we harbor affect influence our behavior as doctors when recommending patients for clinical research trials.

Exceptional performers are able to manage the complexity of being a CRC. Dr. Kingsley discusses the 2 ways you can reign and become an exceptional performer by prioritizing and blocking your time.

There is a lot of drivers for the waste, costs, and delays of getting new innovative therapies to the patients that need them. Dr. Kingsley talks about what precision enrollment means and how it will reduce a lot of waste throughout the industry.

Dr. Kingsley discusses how to handle site level workforce issues by not thinking about CAPA as being linear - start with patients' safety, then data integrity, then root cause analysis, CAPA, study what you did, and act on what you learned from the study. And speaks to Sponsors and CROs about training your CRAs and project managers to think this way so that they can interact with the sites in the same way.

I'm going to talk about the word reSEARCH and why I pronounce it as I do. I frequently have people who will ask me, “why do you pronounce it that way?” Research, if you look it up in the dictionary, you can put the accent on either syllable. It can be reSEARCH or it can be REsearch. Now, in my experience, most people seem to pronounce it REsearch, so why do I choose not to? Why do I choose to put the accent on the second syllable?

Today we are going to talk about commodities and site differentiation. As an example, let's talk about copper. Copper is a commodity. What does that mean? It means there's no differentiation. It means that if I pull copper out of one mine and copper out of a different mine, they're both the same. Copper is copper. Because there is no differentiation, I can't really tell the difference, so they should be priced the same. In fact, if one of the mines is willing to sell it to me cheaper, I should buy it from the cheaper mine because copper is copper. That's what a commodity is. Sites have been commoditized. Actually, we largely did it to ourselves. Sites are undifferentiated. Sponsors and CROs, despite all of their intelligence, still struggle and fail to tell the difference from one site to another.

Today we are going to interview Felicia Irvin, Director of Sales and Marketing for IACT Health, a multi-specialty research site. She has about a decade of experience in finding patients for research trials. She talks to Dr. Kingsley about recruitment methods and strategies.

Dr. Andrew Pippas is an oncologist at John B. Amos Cancer Center in Columbus, GA. Find out how he feels about clinical research and why he thinks patients should participate in research studies. He discusses the future of oncology treatment and gives advice to other oncologists on the best way to get involved in clinical research trials.

How do you predict which sites are going to perform the best on research trials? A recent study found significant evidence that the combination of a certified PI and a certified research coordinator produces far better enrollment, better engagement with patients, and far better quality with fewer errors or protocol deviations. Find out more about how to choose the right site for a research trial.

“Will my other physicians be upset if I enter into a clinical research trial?” The answer is NO. Patients frequently have that fear and I’ve being seeing it for nearly 20 years. Patients will ask me, “If I enter a research trial, will my physician(s) be upset with me?” They wonder If they enter into a research trial with their pulmonologist, will their primary care physician be upset that they did so. Or vice versa - if they enter into a trial with their primary care physician, will their specialist be upset with them. I’ve mentioned in previous episodes that we collaborate with almost all of your physicians. I can tell you definitively that physicians are amazingly supportive of clinical research for lots of reasons. Learn more about these reasons in today's episode.

Today I'm going to answer a question that I frequently get from patients….”if the study drug works for me, can I continue to take it at the end of the trial?” Unfortunately, usually, no. Why? The point of research is to have a systemized process whereby we can look at the safety and efficacy of something stepwise, where piece by piece we learn more about the safety and the efficacy of something. That's why the whole thing exists and that's why we can't just simply give experimental compounds to people without regulatory bodies like FDA, EMA, and Health Canada looking at, vetting, and approving our ability to move forward. The process is slow, but it exists for a reason. It exists to protect you and that's a good thing. The downside is if you got benefit in a research trial, you can't simply stay on the compound that we used. Are there exceptions?

What are virtuous and vicious cycles? They are chains of events, many times very complex chains of events, that are like dominoes: One thing is contributing to another thing, is contributing to a third and a fourth, and they are self-reinforcing - heading in a certain direction. They'll continue in that spiral until an external force breaks the cycle and allows the chain of events to change. These cycles are everywhere. They're in our bodies, in our own biochemistry, self-reinforcing cycles in a direction. They are in economics, in how cities attempt to change neighborhoods from being in dire poverty to entering the middle class, and in the research world. They are even in our own family dynamics: how we raise our kids and how we run our families. But I'm specifically going to talk about the research world and I'm going to talk about the fact that I believe we are in a vicious cycle when it comes to sites and principle investigators, and what I think we need to do about it.

98% of patients who’ve been in a research trial readily say they would enter another – nearly 100 percent! 96% say that they would refer friends and family into research trials. 96% gained such a level of confidence from their experience in research, they would recommend friends and family to research. That's dramatic! As physicians, we have to start talking about research more to our patients. We have to get more publicity around the benefits and the wonderful things of research because it's a tremendous benefit to patients, to physicians, to all of healthcare in general and frankly to our economy. This is how innovation happens. This is how we learned to cure cancer. This is how we make all of these game changing breakthroughs that we're able to. So, patients, if you get involved in research, trust me, you’ll love it and spread the word!

The use of technology at clinical research sites improves efficiency and quality for sites and Sponsors. The use of electronic regulatory binders - eRegulatory - prevents errors and adds to the professionalization of our industry. Find out what regulatory means in the clinical trial world and the benefits of using eRegulatory.