Trial Better: A Clinical Trials Podcast

Tell the audience a little bit about yourself.I’m currently at TriNetX as the Senior Vice President of Clinical Science and Operations, but I’ve been in the clinical and life sciences industry for 22 years. Throughout my experience, I realized a big piece missing in using data to better clinical research was patient-level data. About five and a half years ago, TriNetX came to me and I realized this was a new company up to great things, including using data to advance clinical trial research and planning.For our audience members who aren’t familiar with TriNetX, can you share a little bit about the organization and what role it plays in the clinical research ecosystem?TriNetX was founded in 2013 and commercially launched in early 2016. We are a global health research network and SaaS, on-demand patient data platform that includes advanced analytics and downloadable data sets. We connect the life sciences industry to patient data around the world and provide rapid insight generation to clinical and medical publications to advance thought leadership. We like to tell our customers, “Welcome to the revolution” - our mission is to help conduct trials that are faster and more efficient, so we can bring drugs to market faster and treat patients more quickly than they would have been otherwise.Looking back three to five years ago, there was some criticism of the non-global nature of real world evidence. Has TriNetX responded to these concerns and, if so, can you tell us how?It’s amazing how far we’ve come. Five years ago, TriNetX only had US data, but we knew early on that this wasn’t going to be enough. So, we set our sights on expanding outside the US, first targeting the EU, then the Asia-Pacific region and Latin America. This expansion, with the goal of building a network of data that is truly global, is very important to TriNetX.I’m sure capturing this data at a global scale comes with complications. Have you faced any challenges throughout this expansion?It hasn’t been an easy task to expand. The biggest challenge is how to get global data quickly. Our strategy has included organic growth of our network of sites outside the US, followed by inorganic growth through acquisition of Custodix, the “TriNetX of Europe,” in 2018. Over time, we’ve continued to expand our global footprint in every way; not just through our network, but through our employees, too. We’ve found it’s important to have boots on the ground around the world.Have you seen sponsor motivation to use real world data change over the last few years in response to changes like capturing more global data?We’re getting more and more requests for data outside the US on a daily basis. It’s still hard to come by this data, but there’s a high demand for global data that allows sponsors to optimize trials for patients, sites and PIs, or generate real world evidence of how drugs are being used in different countries.How can real world data help the industry address ongoing issues with representation of diverse patient populations in clinical research?Over the last few months, TriNetX has put an exceptional focus on diversity and inclusion in data. We believe real world data can provide a better understanding of all patient populations across various stratifications including age distribution, race and ethnicity, comorbidity, geography, and more. Sponsors can use real world data to expand their trials and pick sites that have more diverse populations of interest that would still be eligible for the study. They can also explore populations that may not be studied in randomized clinical trials, and how they’re using drugs and reacting to treatments in the real world. Having all this data and a large number of patients in observational studies is helpful for both trial optimization and trial design.According to ERT research, as of last July, 82% of sponsors had adopted some type of virtual trial technologies into their studies. Does TriNetX have a role to play in helping sponsors run effective virtual or hybrid trials?Yes! We’re heavily engaged with many sponsors to address the expanded demand for virtual and decentralized trials. We can work with healthcare organizations to do virtual and hybrid trials, but also use our data to help clients with external control arms, retrospective and prospective observational studies, parallel arms, and dynamic cohort studies (examining the incidence of a condition within patient populations.) These efforts can happen alongside randomized clinical trials, but demonstrate other ways of conducting studies that don’t involve enrolling patients in the old-fashioned way.Do you have any final thoughts you’d like to share with our audience?I think we’re progressing well as an industry in terms of recognizing the power of real world data and what it can do. I encourage everybody listening to do what they can to unlock more real world data and make it usable for our industry. Regulators are now accepting more real world evidence submissions and providing more guidelines on how to do it appropriately. From patients and healthcare organizations, we need more access to data, given it’s all provided with consent and in a de-identified manner. If we, as patients, all allow our data to be used, it’ll allow for bigger research populations, make studies less costly compared to RCTs, and ultimately help reduce drug costs. Using more and more data in research whenever possible is the most ethically sound way to keep moving drug development forward.

Tell us about your experience.After I finished medical school/neurology training, I started on faculty at Indiana University, School of Medicine in the neurology department. I ran a few clinical trials during my time there and became increasingly interested in clinical trial design. Beginning in 1998, I went to work at Eli Lilly and Co. where I focused on late phase work and worked primarily on Alzheimer’s. I started this consulting business about three years ago, and Cogstate was one of the first companies I started consulting with.For our listeners who aren’t as familiar with Alzheimer’s disease, can you explain the specific diagnosis versus one of dementia or mild cognitive impairment?Alzheimer’s is the most common of what we call neurodegenerative diseases; in other words, diseases where brain cells are slowly dying. Alzheimer’s is the most common cause of dementia, but isn’t the only kind of dementia. Recently, the development of biomarkers has allowed clinicians to evaluate if people have the classic pathology to diagnose Alzheimer’s without an autopsy. It turns out, for Alzheimer’s and neurodegenerative diseases you have pathology for many years before you have symptoms. For Alzheimer’s in particular, one of the most important pieces of pathology are amyloid plaques. These plaques are present in the brain for 15-20 years before the onset of any symptoms. After developing these plaques, people develop what’s called mild cognitive impairment which means they experience changes in cognition, but do not meet the strict criteria for dementia. Eventually, people move into mild, moderate, and severe dementia.We know that 50 million people worldwide have dementia and as you state, Alzheimer’s contributes to about two-thirds of cases. Can you tell us a bit more about the current state of Alzheimer’s research?Alzheimer's disease research began with Dr. Alzheimer in 1906, but drug treatment got started in 1990. The first drug approval for Alzheimer’s was a drug called Tacrine in 1993, but this was taken off the market due to causing liver problems. The last new drug approval for Alzheimer’s came in 2003. These medicines are really used to treat the symptoms of the disease. They don’t get at the underlying pathology of the disease. For the last several years, researchers have been more focused on what are typically called disease modifying drugs, which get at the underlying pathology of Alzheimer’s. 99.6% of all Alzheimer's trials fail. Do you think the high failure rates of these trials scare sponsors and prevent them from wanting to invest?That’s been a bit of a rollercoaster. At times, I think that has been the case. There’s a huge unmet need for Alzheimer's research as it is the sixth leading cause of death in the United States. Since we are an aging population, the population growth we will experience will cause the cost of Medicare in the United States to be a trillion dollars a year. Pharmaceutical companies will step up to the plate to try and meet the needs of our population. But then, as you pointed out, when we went through this period when there were so many drugs that were well studied, it just turned out they didn’t work, so there was a time when pharmaceutical companies were skittish about getting into something so risky. What has allowed us to identify these new discoveries and potential advancements in Alzheimer’s disease research?There are a number of factors that come into play. A lot of it is hard work and a lot of it takes longer than one would like. Another aspect is: what do we know about the biology of Alzheimer’s disease and how are we refining the targets? The other advancement in the field is study design. People have learned from past experiences and learned the importance of demonstrating target engagement, meaning ensuring the drug gets into the brain and does what it is supposed to do.It sounds like we may be on the verge of the first disease modifier for Alzheimer’s disease. If it gets approved in the next few months, how will that affect the perspectives on Alzheimer's disease at large?My personal perspective is that it really doesn’t matter if certain drugs are approved or not. From a scientific standpoint, the field knows that the antibodies being researched are giving us a signal. Psychologically, I think it does make a difference for a lot of people, including some of the investors.Are there any final thoughts you would like to share with our audience about Alzheimer's disease research?Yeah, just to reiterate, I think it is a really exciting time for our field. I think we are really starting to get a foothold on treatment modalities, targets, and study designs that can start leading towards more rapid successes. The limiting step in Alzheimer's disease research is recruitment into clinical trials. The only thing I would mention is that if people are having symptoms or even just have a family history, there is a study going on that could be good for you. You shouldn’t go into a clinical trial thinking that the drug will make you better. You should go into a study because people who participate in a clinical trial do better overall than people who don’t. The reason being you get fantastic medical care, you get a lot of attention paid to you, both for Alzheimer’s as well as general medical problems that may come up, and you’re doing something good for society. 

To start off, why don’t you tell us about your experience in the clinical research field and a little bit about yourself.I have had 30 years of experience as an observer of the clinical research enterprise. First, my involvement in management consulting; then I started a publishing company called Center Watch which captured a lot of data and observations about the research enterprise and published that information. After I sold Center Watch, I moved into academia and the nonprofit world and I have been there for about 20 years. Ken, I know you are quite the advocate for building clinical research awareness, and you have certainly been a reliable source of data and insightful metrics on the clinical research industry. Why do you think the general has such a distrust in the pharmaceutical industry and in pharmaceutical development in general?This is such a critical issue and is a perennial problem in the industry. This industry has had questionable practices in R&D as well as the commercial side. There are also some unethical practices that have gotten some visibility, particularly among minority community involvement in government-funded and industry-funded research. As an industry, we have not done a good job of educating patients and the public. As a result, we saw a lack of response and misalignment of messages that come from industry and the clinical research enterprise in general. If you look at the way clinical research is depicted in mass media, a lot of clinical research is depicted as studies that have gone horribly wrong with some dark or unethical practice, and that is often the kind of lesson the public gets when they learn about clinical research.Throughout the pandemic, from February to July 2020, the percentage of the US population who gave the pharmaceutical research industry positive ratings increased by 22%. Some even referred to the industry as “cool”, which is welcome but surprising to hear. Why are we seeing such an uptick on confidence now?This is a very exciting phenomenon, but we have to watch it carefully. To your point, there have been a number of global public opinion polls that have looked at a variety of sectors throughout our economy. The pharmaceutical industry being one of them, and it has enjoyed a bump in positive ratings. It is one of the only sectors where public opinion has maintained this positive bump throughout the pandemic. We think a lot of it has to do with the drug development enterprise being at center stage with a tremendous amount of public visibility. It hasn’t necessarily influenced public trust because awareness around activity rarely translates into behavior.This confidence in clinical research might be rising, but we know the industry still needs to put in the work to repair and rebuild its relationship with the minority population.I think it is widely known now that COVID-19 incidents and severity is much higher in minority communities. This is all part of broader awareness for the critical need of diversity and awareness in clinical research. If you look at a minority or a Caucasian community what you see are very high levels of awareness of clinical research. They will self report that they know what clinical research is, however, there is a significant disconnect between awareness about research and personal involvement in clinical research. Some of it has to do with distrust in clinical research and the drug development process.Really good points, and I can share some of my personal interactions in my circles. Even in the minority population there is a difference of opinion in terms of if they should take the vaccine or not. If you look at healthcare workers in the minority population they feel as though they need to take the vaccine for their own safety, but for those not in the healthcare settings they will say things such as, “I am skeptical”, or “I don’t see the need to take it because of this distrust.” So yes, there is even a difference of opinion in the minority population about how safe these vaccines are.That is such a great point! There is kind of an insular community when you’re in the healthcare environment. We forget as clinical research professionals the vast majority of the public has no real exposure to healthcare unless they’re facing the burden of disease. There are obviously a lot of complexities that come into play. I don’t want to ignore the positives we have seen because despite all that, we were able to develop multiple vaccines much quicker than anyone anticipated. How did the industry work together to make that happen?There is just so much that has happened. Clinical research is heavily regimented and methodical activity. Historically, we not only deviate from it, but we treat the way we operate in a very rigid way. The pandemic forced everyone to become much more accommodating and flexible. There was a recognition that we all need to step in together to protect patient safety. We need to conduct our research activity while helping each other succeed in this environment of high uncertainty with such a huge public health crisis. With that very accommodating and collaborative style, we saw pivoting and adaptation to embrace remote and virtual approaches where we could minimize infection to emphasize patient convenience in these approaches.It is clear that the industry definitely rose to the challenge and collaborated around this common cause. How much of this is going to last beyond the pandemic and do you have any last recommendations around how we can continue to build trust in the industry?As an observer looking in, we often watched how the research enterprise adopts changes in the way we operate and that adoption is incredibly slow. While there is a lot of hope that we will embrace some of the many ways that we have contributed to this accelerated development activity that has yielded some very exciting treatments. I think that we may end up looking at a lot of these adaptations as one time occurrences. Long-term, if we are unable to address the additional complexity that has been introduced through virtual and hybrid trial designs, we may be looking at companies that start to re-think which of the adaptations really deserve full focus and investment.

Tell us a little bit about yourself and 1nHealth.I’m kind of a cross between a life science veteran and an e-commerce veteran. I created 1nHealth based on those philosophies to answer the question, “how do you use compelling marketing to incite individuals to take action?” At 1nHealth, we are putting an advertising catalyst in front of individuals in hopes of getting them to enroll in clinical trials. Early last year, the COVID-19 pandemic was beginning to impact sponsors' ability to run clinical trials. What kinds of choices did you see them making?For the first stage, sponsors’ and CROs initial decision was to wait. The evening the NBA cancelled the season was kind of the stark flag in the sand that this year was going to be very different. After that, sponsors and CROs had to adapt and create a more robust strategy to recruit participants, thinking beyond the standard playbook of bringing participants into sites.We saw sponsors choose to go the virtual route. Did we start to see that in the patient recruitment space as well? How are patient recruitment vendors adapting to this shift to more decentralized trials?You can take the same protocol and apply a digital lense to it to get the same results. Overall, what we have seen is instead of looking at sites as the bread and butter for patient recruitment, we are seeing studies and RFPs come to us with digital as the central point to recruitment with sites as the adjunct for recruitment. How was 1nHealth able to effectively reach people throughout the pandemic? What every digital recruitment firm is going to do is put ads in front of people and hope they take some action. Here at 1nHealth, we believe that marketing around clinical trials is about starting a conversation. We are able to reach folks for clinical trials because they are what is outside the “norm” for clinical trial recruitment. Second, we are using creative content that belongs on their newsfeed or search bar. The clinical research industry has been accused of being slow to adopt AI compared to other industries. For sponsors who have found themselves turning to digital solutions in response to COVID, what advice would you give them? How should they adjust their patient recruitment strategies?The status quo does need some shaking up. In many cases sponsors are used to sticking to what is required of the participants. We want to get sponsors to think about what is going to get people to read more - it has to be about the patient when we think about what patient centricity online looks like. We want to create content that is native to the environment and gets them to take the next step. What do you think the state of patient recruitment will be after COVID-19? Do you think it will be predominantly digital or will site-based trials come back?I think it’s going to be somewhere in the middle. COVID forced us to stay in our houses for a while, and as that lifts we’ll see the requirement for sites to be part of studies still remains. I think there is a seismic shift that is happening in the push for decentralized trials. With all of that in mind, digital will become more central to trials as some trials cannot function without sites. Are there any final thoughts you would like to share with our audience?I just want to reinforce how we have an industry that is so sophisticated and technical. We need to remember that these are people who are scrolling through their feed and come across a trial ad. Sponsors need to work to throw out sterile advertising copy because the way we talk to them is what compels them to move forward in the study. 

Jim, tell us a little bit about yourself and your work at ACRP.I started my career at Eli Lilly for 24 years before moving to Quintiles, now known as IQVIA, for 5 years. After spending the following five years consulting, I became the executive director for ACRP.ACRP recently released some data on the state of the clinical trial workforce. I want to dive into what that data revealed. What trends are you seeing in clinical research career opportunities right now?Recent trends in clinical research career opportunities include a disproportionate growth rate of clinical studies compared to the size of the workforce. We believe strongly that we need to close this gap to get therapies to market as quickly as possible.What might a typical career path look like for someone entering the clinical research industry? Do you need to have a scientific background to be successful in clinical research?Right now, I'm not sure there is a typical career path. Most people who end up in clinical research typically come into their positions by chance. That lack of clarity in career entrance and development is a huge problem.In previous episodes, we’ve heard about the importance of recruiting diverse patients for clinical research. Can you speak on the importance of having a diverse workforce in clinical research as well?We feel like we can kill two birds with one stone so to speak. Growing the diversity of the workforce can in turn grow the diversity of those enrolled in clinical trials.What are the potential consequences of clinical trial growth outpacing clinical trial employment?A potential consequence of the outpace in growth between clinical studies and the workforce in clinical studies is that we won’t have enough people to conduct studies to the extent that we need them to. This will be a bottleneck in the development pipeline.What can sites, sponsors or CROs do to encourage interest in joining the clinical research industry?The more variance you have, the more likely you are to have poor quality, and unfortunately that’s the case in clinical research now. It’s critical that we begin defining competencies for positions in our industry. When we gain industry alignment around these competencies, we can begin to train individuals on them, and then validate that people actually have them. This is the only area in healthcare where there are no real standardized requirements or competencies. We need to change that.

Fabian, tell us a little bit about yourself and your experience.I’m Colombian, but I was raised in northern Virginia. I got a bilingual medical training and moved on to research after my residency. I soon realized I wasn’t keen on the monotony of regular medical practice. I ended up moving into clinical trials and research and have been in the industry ever since.You’re a key member of the SCRS’s Diversity Awareness Program. Can you tell us about your history with the program?SCRS started this program because there was a need and continues to be a need to not just raise awareness, but to do something about the lack of diverse populations that participate in clinical trials. When I heard about the idea for SCRS to focus on improving diversity, I knew that I had to be involved.What are the most important lessons you’ve learned from your participation in SCRS’s Diversity Awareness Program?When it comes to pharma sponsors of all sizes and CROs, there was a lack of awareness of the issue of diversity. Many people I spoke to did not know about the FDASIA (Safety and Innovation Act) Section 907, which states the importance of diversity in clinical research. I knew it was important to increase awareness of this policy, even among sponsors who I wasn’t working with, because I recognized its importance and potential to change clinical trials.What can happen when sites are greedy with their information or don’t share amongst themselves the strategies they’ve utilized to improve diversity?There’s no point in having “gold nuggets” of information if they aren’t shared. The reason we do clinical trials is to improve medicine and one day we or someone we care about may need that drug. So if we’re successful at a task, we need to share what we’ve learned so other people can take something away from our successes and our failures. Passing on those gold nuggets is critical to improving our work overall.Can you tell us a little bit about the FDA Snapshots website?This website tells you what drug was recently approved and breaks down the demographics of the participants. What we can take away from this information is that if the medication was not tested on a diverse population, it may not work on every single person. And if it doesn’t work, we haven’t done our due diligence or been good scientists. This is useful because it gives us an idea of which populations we need to do a better job at targeting next time around.What can other sites do to improve the diversity of the populations they’re enrolling? Look out the window of your office, look at people in the stores, and go and understand the community that’s around you. If you aren’t seeing a reflection of that population in your patients, then there’s a disconnect that’s fixed by getting to know your neighbors and community. Meeting church leaders and business owners is a great place to start. It’s more challenging during COVID, but as businesses open up, you can go and safely introduce yourself.How can sites adapt during COVID-19 to ensure they’re still making their presence known in their communities?Still having outdoor signage to let people know you’re there is important. Because we can’t go out in the community much, we’re utilizing social media like Facebook Live to talk and engage with people in the community. We don’t want to bore them, so we connect with them by providing them with useful information on top of sharing what research we’re working on. This allows us to maintain a presence so that community members know we’re still here and ready to help.What does it really mean to have culturally competent staff at your site?Cultural competency and being aware of the nuances of different cultures is important so you don’t offend or lose anyone. I was vision screening a Vietnamese patient who didn’t know how to pronounce certain letters of the US alphabet used in the vision chart, because those letters weren’t used in her language, and shame on me for not knowing that.We need to understand what works or doesn’t work for each individual. This will help ensure they’re comfortable to engage in the study. What considerations should sites keep in mind when developing effective communications or marketing strategy to reach the patients in their communities?It’s important to know that not everyone has insurance or legal status in some communities. If you want these patients to participate, tell them they don’t need to worry about the insurance and that you’ll never share their personal information with ICE or the police. It’s critical to let them know they’re in a safe environment. Transparency on the site’s end is key because it can help patients let their guard down and even encourage their family or other members of their communities to participate. Tell us about your site and the successful (or unsuccessful) strategies you’ve implemented to make sure your patients are representative of your community.My first study was a pediatric study. I took all of my advertising money and put it into a bus campaign because I assumed all kids rode the bus. The ads ran for four months and I got three calls, none of which were from actual patients. I realized I needed to do a better job of finding the right patients. So instead, I went to daycares, talked to the parents, and started to make the right connections.If we don’t really understand our patient populations and where we can find them, it’s not going to work. It’s critical that we work on that understanding because we don’t want to waste time and efforts; we want to be good stewards of the sponsors we’re working with and be considerate of spending the marketing dollars appropriately. Tell everybody a little bit about your advocacy for health literacy and your TV show.I’ve always wanted to promote health literacy. The terminology and acronyms that we don’t think twice about can be confusing for people outside the industry – and not just that, but also for people from outside the country or culture.To accomplish my goal of educating the community, we started the Emerson Diversity Health Foundation. It’s designed to provide community outreach and education awareness. We partnered with sponsors to create a TV show, “Tu Salud Tu Familia” (Your Health Your Family), that’s been on for a year and a half and is now Emmy-nominated. It airs every Saturday morning and we are joined by elected officials, thought leaders from industry organizations, and patients who help us explore a health topic in simple terms. We reach 50,000 people live, and our social media presence has helped us expand our reach all across the country even though we’re a local show.Again, the success of this doesn’t just benefit me, it benefits everyone. An educated patient knows the value of healthcare and research and knows where to get access to these important resources.Watch Tu Salud Tu Familia on YouTube (English subtitles are available) or follow the show on Facebook, Instagram, and Twitter.

Fabian, tell us a little bit about yourself and your experience.I’m Colombian, but I was raised in northern Virginia. I got a bilingual medical training and moved on to research after my residency. I soon realized I wasn’t keen on the monotony of regular medical practice. I ended up moving into clinical trials and research and have been in the industry ever since.You’re a key member of the SCRS’s Diversity Awareness Program. Can you tell us about your history with the program?SCRS started this program because there was a need and continues to be a need to not just raise awareness, but to do something about the lack of diverse populations that participate in clinical trials. When I heard about the idea for SCRS to focus on improving diversity, I knew that I had to be involved.What are the most important lessons you’ve learned from your participation in SCRS’s Diversity Awareness Program?When it comes to pharma sponsors of all sizes and CROs, there was a lack of awareness of the issue of diversity. Many people I spoke to did not know about the FDASIA (Safety and Innovation Act) Section 907, which states the importance of diversity in clinical research. I knew it was important to increase awareness of this policy, even among sponsors who I wasn’t working with, because I recognized its importance and potential to change clinical trials.What can happen when sites are greedy with their information or don’t share amongst themselves the strategies they’ve utilized to improve diversity?There’s no point in having “gold nuggets” of information if they aren’t shared. The reason we do clinical trials is to improve medicine and one day we or someone we care about may need that drug. So if we’re successful at a task, we need to share what we’ve learned so other people can take something away from our successes and our failures. Passing on those gold nuggets is critical to improving our work overall.Can you tell us a little bit about the FDA Snapshots website?This website tells you what drug was recently approved and breaks down the demographics of the participants. What we can take away from this information is that if the medication was not tested on a diverse population, it may not work on every single person. And if it doesn’t work, we haven’t done our due diligence or been good scientists. This is useful because it gives us an idea of which populations we need to do a better job at targeting next time around.What can other sites do to improve the diversity of the populations they’re enrolling? Subscribe to learn more. Get access to the full episode by signing up for our mailing list at Trial Better.How can sites adapt during COVID-19 to ensure they’re still making their presence known in their communities?Subscribe to learn more. Get access to the full episode by signing up for our mailing list at Trial Better.What does it really mean to have culturally competent staff at your site?Subscribe to learn more. Get access to the full episode by signing up for our mailing list at Trial Better. What considerations should sites keep in mind when developing effective communications or marketing strategy to reach the patients in their communities?Subscribe to learn more. Get access to the full episode by signing up for our mailing list at Trial Better. Tell us about your site and the successful (or unsuccessful) strategies you’ve implemented to make sure your patients are representative of your community.Subscribe to learn more. Get access to the full episode by signing up for our mailing list at Trial Better. Tell everybody a little bit about your advocacy for health literacy and your TV show.Subscribe to learn more. Get access to the full episode by signing up for our mailing list at Trial Better.

Host Jason Eger is joined by Dr. Diana Foster, Vice President of Strategy and Special Projects at the Society for Clinical Research Sites, to discuss how clinical research sites can help the industry improve patient diversity in clinical research.

Tell us about TrialScope and your experience.I am the Vice President of Patient Engagement at TrialScope. I used to work at the Michael J. Fox Foundation for Parkinson’s Research and also had my own company, Clinical Trial Connect, before it was acquired by TrialScope last year. I’ve been working in the clinical trial recruitment world for the past ten years. I am overseeing a new product called TrialScope Connect, which sets sponsors up for success when it comes to clinical trial improvements. What typically motivates patients in a clinical trial?Every patient is different and every trial is different. People are dealing with diseases that are often very urgent or difficult. Having a path towards a better prognosis, extending your life, and improving your quality of life are all factors that people consider when it comes to clinical trials. There are people who participate in clinical trials who know it might not improve their quality of life, but it’s something they want to do for the next generation. For other people, there is an awareness in recognizing no cure has ever come on the drug shelves without going through the clinical trial process, and they want to do their part to make sure science continues to move forward.Tell us about the journey of a patient in a clinical trial.The journey starts when a patient is first diagnosed with a condition, but following that, there are many different places where someone might become aware of a clinical trial for the first time. At that point, patients need an educational component to become familiar with the different terminology. Once a patient has that knowledge, they can decide if they are interested in moving forward and participating in research. Then, they have to find the right trial for them. Every trial is different and has different inclusion and exclusion criteria. Every trial is run at different site locations. There is a challenge around finding the right opportunities. Once a patient does identify an opportunity, getting in touch with that site is the next step. Then they go through the enrollment process. Ultimately, a patient will learn if they are eligible to participate in that trial. If not, they’ll have to restart their search process.Do you see patients becoming more engaged in clinical trials and in general has this impacted clinical research?Today, people are used to being very informed. Patients are surprised when they start the journey at how analog it is and how many roadblocks exist. One of the things that is problematic is that a lot of patients don’t know how to search for a trial that is the right fit for them. There is no easy tool to solve this problem, and patients have to tediously review clinical trial listings. In addition, if patients aren’t aware of how to search proactively, they’ll never know their full range of options. This denies them an informed choice. This is how standard trial-centric matching works, where the finish line is one trial and a lot of times a funnel is used to see how many patients need to be at the top of the funnel to get to the trial’s required number of patients. What’s unfortunate is that for all of the patients that weren’t eligible there’s not a great next step of action for them. For the enrolled, they might have missed out on the opportunity to be in another trial since they were only being screened for this specific one. We think about patient centric trial matching, putting the patient in the middle and asking what trials does this patient actually match to and allow them to make an informed decision. What can the industry do to get to this patient-centric model?There’s a lot of companies that are tackling this and whether the solution is a website or an integration, people are trying to do right by patients. It’s an opportunity to standardize how we talk about eligibility criteria and the benefit is that companies don’t have to reinvent the wheel. With TrialScope, they can now have a best-in-class platform to match a patient to all the trials that are a good fit for them.What can sponsors do to motivate and educate the recruiters of their trials? How do we get them to be more knowledgeable about the trials that are out there?The physicians are challenging. They have 15 minutes or less with a patient. Anything that is disruptive to their flow or takes up more time is something they aren’t going to use. However, there is a solution where they can help the patient to make a decision that is within the time of their appointment. Patients can review their matches in advance, get material in the waiting room, and by the time they’re with their doctor they have a decision and are fully informed. Now, the doctor can talk to them about that specific trial. A lot of solutions like that are possible.How do sponsors ensure that they are being mindful throughout the patient’s journey during all of the phases?Something that happens is that patients spend a lot of time reviewing their matches and they never hear back from the site.  Sponsors can be more communicative with patients, even in an automated way, to let them know when a site has stopped recruiting. Let’s make sure no patient goes down a dead end and is waiting for a response that they’ll never get.For the people that do enroll, the journey continues for them. A lot of times patients don’t know what happened with the trial. Making plain language summaries available in different languages and sharing patient data with those who participated in the trial can be steps towards increasing patient satisfaction with their trial experiences.

Speaking from a general safety perspective, as well as a cardiac safety perspective, what challenges have you observed in clinical trials resulting from the COVID-19 pandemic? [3:07]I speak for myself and others, no one trained us for this and we had to quickly react. We want to ensure the safety of the participant as well as making sure the data is right. We have to consider what is in the best interest of the patient and how we can ensure that the data that is collected will be able to be analyzed at the end of the study. We had to rethink what to do, but the situation differs. For a company in Phase I with very little information, it’s not the same as a Phase IV clinical study. However, the common ground is that they try their best to maintain the integrity of the trial. In particular with cardiac safety, there are certain parts of the clinical trial where remote monitoring can continue to be done.What approaches have you seen employed in managing these challenges? [8:40]What I see the most is that one size does not fit all. Certain studies you cannot stop. Overall, what we have been trying to do is hold a very careful assessment of the conditions of the patients under study and the risks vs. the benefits of stopping or continuing the study. Thinking back, what do you think was the general consensus in the industry with respect to virtual clinic trials one year ago, versus today?  Was this something under discussion?  If so, how was it meant to be applied, versus what are you seeing now, and versus what we may see in the future? [12:00]One year ago virtual trials was an interesting topic that needed to be further developed and was worth discussing. Now, it is something that we jumped into in order to ensure trial integrity and safety of the patient. What do you do when you’re in the middle of a study and you realize you cannot collect that data and if you want to complete the study, changes have to be made? If you were supposed to collect the data in a certain way at a certain location, now you have to modify what you had done before in order to ensure the safety of the patient and the accuracy of the data. Virtual studies was no longer an idea, but an urgent need that had to be implemented immediately.As we adapt to the current paradigm, certain changes are occurring in the way we all operate. There’s a lot of talk now of a hybrid model in clinical trials as a means to continue studies during this pandemic. Of these changes, what do you see as temporary, versus a change reflective of the future of safety monitoring in clinical trials? [17:48]During these times we are getting a crash course on things like digital collection of many different outcomes and safety monitoring that in the past we were underusing or didn’t know how to properly implement. This is pushing us to better define, monitor and focus on the essentials in clinical studies. If we can make it easier for patients to be a part of clinical studies, there might be a higher participation of people that want to volunteer. If we can take advantage of the tools that we currently have available and the others that are yet to be developed, there will be more real life data. From the patient's perspective, do you have any thoughts as to how they might view clinical trial participation in context of the COVID-19 pandemic? [20:33]If you can ensure patient safety and can communicate that the setting that’s been set up in a study is ensuring safety for them, that will make them feel reassured. We are making it easier for them to complete the different assessments. In order to do so, there has to be adequate training to ensure the safety of the patients and adequate data is collected.

How did you end up in patient advocacy?At the time of her first diagnosis, Deb was a computer company executive. Along with her husband (also a cancer survivor), she got involved with an oncology patient advocacy group. This was in the early 1990s when very little was known about effective cancer treatments, and she felt that this was important to changeCan you explain the role of a patient advocate?A patient advocate contributes in a dramatic way to improve the experience of patients they don’t know through direct patient support, political advocacy, fundraising, and watchdog advocacy. A research advocate takes a long-term partnership approach. They focus on improving and speeding research results and ensure patient results and things that are important to the patient community, not just the scientific community, are a major focus.Why do you believe it’s so important to speak up for the patient in clinical research?Typically research has been all about science, product development, and regulatory compliance. No one has truly focused on the patient experience or the fact that the patient is the true end-user. This needs to change, and clinical research should set goals for finding better treatments, not just more, that give patients the improvements they’re looking for.Do you find there’s usually a difference between the answers patients are looking for vs. answers sponsors are looking for?While they are different, they can be considered together so we can get to the answer we’re all looking for. Companies may be focused on getting label approval from regulatory agencies, rather than the usefulness of this product and how it can fit into the rest of a patient’s life. This is where the patient voice is crucial, because it helps us complete the picture and cover aspects that are actually important to the patient community.What are the risks of a lack of patient focus in clinical trial design, or in the industry at large?Not recognizing the patient as the end-user can negatively impact the results patients get from a treatment. By involving patient advocates in the trial design process, sponsors can avoid or eliminate barriers that prevent individuals from enrolling in a clinical trial. Sponsors can also turn to adaptive trial design, which celebrated its 50th anniversary in 2019, as a potential way to improve the patient experience.Does the method of incorporating patient centricity vary based on therapeutic area or indication?It does vary. In oncology, for example, cancer is very multi-faceted; it can be chronic, life-threatening, acute, and so on). The type of cancer or patient situation can make a big difference in terms of what will be effective.Currently, the industry approach to “patient centricity” still views the patient as a target to get data from. To address this, we need to start thinking “what’s in it for patients?” instead of “what’s in it for me (as a sponsor)?” Focus on patient needs ensures that regulatory and product concerns will also naturally be addressed.Are there any advancements that you’ve seen improve the patient experience in the last few years, or any you anticipate to come? How can the industry implement these changes?Things are definitely improving, and more people are understanding the difference in perspectives among trial stakeholders. However, the scientific and medical communities need to be more in line with the patient perspective of a “cure”. There also needs to be an increased recognition of the fact that clinical research is often an endurance test for patients, particularly when sponsors are looking to address retention or compliance issues.Can you share an example of a sponsor who experienced some benefit after proactively choosing to keep the patient at the center of their trial?A breast cancer study funded in part by the National Cancer Institute was the first trial that explored neoadjuvant therapy. Patient advocates were involved in the trial development process from the beginning. As a result, the study recruited patients quicker, required fewer amendments, cost less, and was completed faster. Bringing in patient advocates early was crucial to the trial’s success..Do you have any final thoughts you’d like to share?We’ve all heard the terms “real-world data” and “real-world evidence.” The concept is important and has a lot of promise, but we have to think about what’s in it for patients. A shift from real-world data (raw material), to real-world evidence (analytics) to real-world answers is key to addressing what patients, families, and doctors really need and want.

Introduction [00:55]Dr. David Albert of AliveCor explains how patient-collected data can solve some of the problems facing clinical trials during the COVID-19 pandemic, as well as the long-term outlook on changes in data collection for clinical research.What is the AliveCor KardiaMobile 6L and how does it work? [01:43]The AliveCor KardiaMobile 6L is a 6-lead device for patient-collected ECG/EKG reads.How is the KardiaMobile 6L being used today in light of the COVID-19 pandemic and subsequent changes in FDA regulations? [03:21]AliveCor received the FDA’s approval for emergency use of the KardiaMobile 6L. Some drugs being tested as treatments for COVID-19 may cause QT prolongation, potentially leading to a serious cardiac arrhythmia. The KardiaMobile 6L is capable of monitoring QTc and able to keep people safe while they’re using experimental COVID-19 treatments.How can the KardiaMobile 6L make it easier for doctors to keep patients safe during COVID-19? [05:14]Taking ECGs in hospitals treating patients with coronavirus requires staff to sterilize the machine and use personal protective equipment, when those resources may be better used on the “front lines” in hospitals. Now, using the KardiaMobile 6L, patients are able to complete their own ECGs / EKGs without having to use valuable PPE or put ECG/ EKG techs at risk.How do you think we can solve the problem of successfully conducting clinical trials today during stay-at-home mandates?[07:15]There are increasing demands from sponsors who want to do virtual trials or conduct trials within unique venues, like refugee camps. In these cases, the KardiaMobile 6L can provide a solution to measure the potential impacts of a treatment on a patient’s QT interval.Should clinical trials sponsors have any concerns about the integrity of remote ECG / EKG data collection?[08:54]The KardiaMobile technology has proven that a person if trained correctly and with practice, can collect clinical-quality ECGs at home by themselves. It’s also been demonstrated that this technology can be used even in difficult populations.Do you think there’s going to be a permanent move towards at-home monitoring in clinical research following the changes put in place in response to COVID-19?[11:00]COVID-19 has been the greatest catalyst to change in primary care; for example, telemedicine has become a standard way of providing care. Patients have responded positively to it. This sentiment will likely carry over into the clinical research industry.What do you see as the benefits of at-home ECG / EKG collection by the patient?[12:28]People are more relaxed and comfortable at home, which can lead to improved data (similar to the white coat effect in collecting blood pressure data at home.) Sometimes patients may experience conditions like atrial fibrillation at home; by the time they get to the hospital or doctor, it’s passed. With personal ECG/ EKG devices, patients can document their experiences without ever going to the doctor. Remote management and remote patient monitoring are trends that are here to stay following COVID-19.How do you think remote data collection solutions will continue to evolve? What other trends do you see coming in the industry?[15:09]“Digital health” is just becoming health. The smartphone is now incorporated into every part of our lives; that’s going to become the principal entry point for many people into healthcare. Smart devices keep becoming more and more sophisticated, and we’ll continue to see more remote monitoring and attempts to prevent illness by catching issues early and encouraging changes in lifestyle and healthcare.

Introduction [00:55]Nadeeka Dias and Chris Watson from ERT discuss the race for a coronavirus vaccine and take a deeper dive into how sponsors and CROs can use technology to address the unique challenges of vaccine trials. What are the specific challenges sponsors face in trying to create a COVID-19 vaccine? [02:10]The real challenge is that the threat is now, so time is not on our side. However, good clinical research takes time. Because there are currently no approved vaccines or treatments for COVID-19, researchers are working on two types of trials: trials to test treatments for patients who already have the disease and trials to test a COVID-19 vaccine.Even though these vaccine trials are accelerated and researchers and the FDA are moving quickly, it’s still going to take a lot of time to find a vaccine that works. While collecting data in a COVID-19 vaccine trial is going to be similar to any other vaccine trial, patient recruitment will be harder and sponsors will have to ensure that patients who are enrolled aren’t asymptomatic. What are the challenges that are unique to vaccine trials? [04:21]Vaccine trials are often developed in response to a new plague. Because of this, clinical development teams need to collaborate quickly to mitigate trial risks and delays. These studies also require a lot of physician oversight of patient safety and adverse events. Additionally, because vaccine trials often enroll large numbers of healthy volunteers across diverse demographics, it’s important to be mindful about how sponsors will effectively collect a very large volume of data. Lastly, sponsors should consider how they can keep their patients engaged, especially as the vaccine trial transitions into a more observational phase.What are the challenges of using paper in vaccine trials? [06:05]Because paper is a quick way to respond to the needs of vaccine studies, paper has always been the default option for data collection in these trials. What isn’t always taken into account is the volume of data that will need to be transcribed from paper into a repository; a typical vaccine trial can produce millions of data points. This volume of data should convince sponsors to contemplate using electronic data collection. What advice would you give sponsors still using paper in their vaccine trials?[07:27]It’s important to consider the impact of still using paper not just on data collection but on data analysis. If all of the data is regularly uploaded into an electronic database, the sponsor will likely be able to get results quicker and achieve database lock sooner compared to using paper. An electronic platform also provides real-time access to patient data, making it easier for clinicians to monitor patient safety.How can sponsors already using a digital solution improve their data collection?[08:45]Electronic always gives you better data quality, but to maximize it, you need to remember the end user: the patient. Engage with patients and facilitate their journey within the clinical space so ultimately they’re providing the quality data you need to determine the results of the study.Flexible provisioning or BYOD is an electronic solution that makes electronic data capture very affordable for vaccine studies and integrates well into the everyday lives of patients.How can a sponsor get started with electronic data collection?[10:59]If sponsors have reservations about starting to collect data electronically, they can always run a small pilot study in one particular territory using these techniques. Comparing the results in that territory to results in the others should make it clear whether or not a sponsor should pursue electronic data collection in their studies.Once this data is collected, what tools are out there for sponsors to use to help them analyze and visualize the results?[12:15]Instead of putting data into the system at the end of a study (as is done with paper data collection), data is added to the system throughout the study. A strong reporting platform that can support analysis of millions of data points and give you early insights into how the vaccine is progressing is critical.What are the ways we can use digital to keep healthy volunteers engaged in vaccine trials?[13:25]Incorporating technology into a well-thought-out study design can improve long-term patient engagement. A key motivator for patients is knowing that a clinician is reviewing the information they’re entering in their diaries. A digital solution can be beneficial here; concerning data can be quickly flagged and sites can easily maintain communication with patients.Any final thoughts?[15:15]The circumstances we’re in are unprecedented, but there are many brilliant people working together to discover treatments and vaccines. It’s important that the industry supports these studies by implementing known and established best practices for data collection.The search for a COVID-19 vaccine and cure is an ideal opportunity to embrace, not fear, the use of technology in clinical research. The patients and healthy individuals who want to be involved in these trials are embracing technology themselves; sponsors should follow their lead.

IntroductionWe welcome Nicholas Conn from Heart Health Intelligence and Jean-Phillippe Couderc from VPG Medical as he joins Trial Better to discuss passive health monitoring and the smart toilet seat.What is the Heart Seat and what does it do? The Heart Seat is a cardiovascular monitoring system integrated into a toilet seat. This allows you to monitor a comprehensive set of measurements in the home without requiring patients to change their behavior at all. The Heart Seat automatically starts downloading data when the user sits down; that data is then uploaded to the cloud. It can measure over nine clinically relevant cardiac parameters including blood pressure and cardiac output.What is the user experience of the Heart Seat like?The seat has the same standard hinge mounting as a regular toilet seat. It’s as simple as popping off the old toilet seat and replacing it with the Heart Seat, which is completely battery powered. The version coming to market will have full cellular and WiFi capabilities built into it.What’s the timeline and process for bringing the Heart Seat to market?Right now, Heart Health Intelligence is working through the required regulatory processes to bring the Heart Seat to market. They anticipate finishing development and submitting for final FDA approval by 2021, and are targeting the end of 2021 for the initial product launch.Is there anything different that needs to be done to achieve regulatory approval for passive monitoring devices versus achieving approval for new drug therapies?Companies seeking approval for passive monitoring devices must prove that high quality data can be collected using the device. So far, nobody has gotten approval from the FDA for these types of devices. While the FDA is interested in understanding the impact the device and passive acquiring procedures can have on data, they also want to ensure passive monitoring devices can produce robust data.How can the introduction of passive health monitoring devices impact clinical trials?Integrating passive monitoring into clinical trials will make participating in trials less burdensome for patients. One would expect that this type of technology will not only lead to more data but will also increase patient compliance and enrollment in clinical trials. Passive health monitoring can also be looked at as a trigger for virtual clinical trials.Besides regulatory approval, what other challenges might passive health monitoring devices like Heart Seat face?One of the big challenges with adopting any in-home monitoring technology is how it ends up being used in clinical practice. Passive health monitoring devices put massive amounts of data in the hands of providers and study teams that are already extremely busy. Producers of passive health monitoring devices are also digital services companies that have a responsibility to figure out how to reduce this burden in order to achieve widespread adoption.How can we ensure patients are compliant with these devices?These devices require much less effort from the patient in order to achieve compliance. The point of these devices is that patients don’t need to change their behavior in order to provide the data that sponsors need.Do you have any final thoughts on the future of passive health monitoring?One of the most exciting things about these technologies is that we don’t know what we’ll discover when we capture data at such a high frequency and with such high levels of adherence. It may enable us to develop better, safer medications and make improvements in the quality of care. There are also opportunities for advancements through machine learning. These devices and the data that they capture can be used for other purposes and applications that we can’t yet imagine.

IntroDawn Patterson, ERT Director of Respiratory Solutions, is joined by Kevin McCarthy, ERT Clinical Overread Specialist and member of the ATS/ERS 2019 Spirometry Update Task Force. They’ll explore the implications of the October 2019 ATS/ERS update to their pulmonary function testing guidance. ERT was the only data and technology vendor involved in the update.What are the ATS/ERS guidelines?These guidelines represent what can be considered as worldwide standards that ensure the quality of pulmonary function measurements. This type of measurement is somewhat unique in that it requires a high degree of patient understanding and cooperation.When were the ATS/ERS guidelines last updated?Spirometry standards were first published 40 years ago, and updated approximately every 10-15 years since. The last time they were updated prior to 2019 was 2005.How did you get involved in the task force that was responsible for updating the guidelines?I was approached by the ATS/ERS to participate on a committee to develop an accreditation for pulmonary function laboratories. While working on that project, I was asked if I’d be interested in participating on the update task force.How is this guidance used in clinical research?Typically, ATS/ERS guidelines are incorporated in testing protocol for clinical trials. This is important in guaranteeing comparability of tests obtained from multiple global testing sites. In the 2019 guidelines, it’s specified that these standards represent the minimum criteria that must be met for clinical spirometry only - not necessarily for research or occupational surveillance. In clinical trials, sometimes the bar should be set higher.What are the most important changes in the new spirometry guidelines?One of the most important changes involves the recognition that the forced exhalation could be performed perfectly but still give erroneously low results. The new standards emphasize the need to look at the subject for feedback, and gives detailed guidance to site operators on how to vigorously coach patients to full inflation.The new standards also stipulate that the procedure does not end with the forced exhalation. At the end of the forced exhalation, the subject is again vigorously coached to full inflation, allowing for a comparison to the FVC that allows operators to verify the forced exhalation started from full inflation.In recognition that pediatric patients and patients with interstitial lung disease had difficulty in meeting end-of-test acceptability criteria, these acceptability criteria were redefined in a manner that accommodates the lung physiology of these groups.Finally, the updated standards provide a new letter grading standard for acceptability based on the two main forced spirometry parameters. In the old standards, if an effort failed to meet the start of test criteria, the effort was considered to be unusable for reporting. In the new standards, an effort that is unusable for FEV1 may be acceptable for FVC and vice versa.Are there any minor changes to the guidance that people need to look out for?This document makes recommendations to the manufacturers about features that they should provide for the users of their testing equipment. One of the recommendations made was that the manufacturers provide standard lists of operator comments. These lists allow the operator to quickly select a comment from a list (in addition to adding free text) to provide insight and context about quality issues for study teams or physicians.How will this new guidance impact sites and patients in respiratory clinical trials?This new update of the spirometry standards will likely reduce the number of times a patient will have to perform the forced expiratory maneuver to achieve acceptability, improve data repeatability and improve data quality by verifying all efforts start from full inflation. This should result in a big win for sponsors, especially in studies involving pediatric patients and patients with interstitial lung disease.Final thoughts:There was an increased recognition of the importance of the operator administering the test in getting quality results. Operator training and the attainment and maintenance of competency must be integrated in any spirometry testing service.    

What trends have you seen in respiratory in 2019?In previous years, there were a number of blockbuster drugs developed for conditions like asthma and COPD. However, these drugs are beginning to move off-patent, so the industry is beginning to see studies for generics taking place. Because these blockbuster drugs are still on the market, sponsors are instead looking for new indications to apply these treatments to, where they might achieve small benefits. In order to find these incremental effects, the size of the study must increase. However, respiratory trials are not immune from the industry-wide patient recruitment issue. Additionally, these new products are fairly niche and respond to a small subset of patients; as drug companies are testing a lot of the same mechanisms, this leads to more competition for an already small patient population. The shift in clinical research towards personalized medicine continues to exacerbate the problem. Finally, this new search for small treatment effects requires very accurate data.What do you anticipate respiratory drug development looks like in 2020 and beyond?The key change is going to be a stronger focus on data quality and the importance of understanding exactly how the drug works in every individual patient. In order to do this, the challenge of data variability needs to be addressed by a shift towards research-grade quality lung function testing. This will allow the data to reflect small treatment effects. The updated ATS/ERS guidance published in October 2019 recognizes the importance of reducing data variability.How does this new guidance and focus on reducing data variability affect the industry in general?High quality data often comes with a higher cost but the potential rewards are huge, because data variability has an impact on every phase of development and can compromise decision-making and revenue potential. We’ve learned that the results of a trial can be undermined even if only 10% of the data is corrupt.

What trends have you seen in imaging in 2019?One of the biggest trends has been an increase in demand for imaging over the last year as more and more trials have begun to require imaging as a primary endpoint. This has always been common in oncology studies in particular, but not the industry is starting to use imaging as a primary endpoint in other indications as well.What do you think the future looks like?In 2020 and beyond, there will be a push toward siteless trials. In imaging, we may be able to use subjects who live far from a primary site and previously would have had to travel for imaging. They’ll be able to visit a local center for imaging instead, and have those images uploaded remotely to a platform for centralized assessment. In fact, ERT’s platform allows this already: sites and local centers are able to complete uploads.How has artificial intelligence had an impact on imaging?We can use artificial intelligence to determine whether or not an image is appropriate. By using the information we’ve gathered over the past 15 years, we’ve trained an AI algorithm to determine the quality of an image. AI can also pre-segment images and so readers don’t define boundaries within the image themselves. This reduces variability and gives sponsors additional information that they may not have gotten from simplified criteria. Artificial intelligence can be used to improve efficiency and cost, and also maximizes the data being collected, which is particularly important when a patient is being exposed to radiation during the imaging process.

What trends have you seen in eCOA in 2019?There’s been a shift in the regulatory landscape over the past year, shaped by an ongoing effort since the launch of 21st Century Cures Act to update patient-centered outcomes. The FDA has also taken on the task of updating guidance to industry published in 2009 on the use of PROs, culminating in the drafting of a fourth new guidance. In early 2020, we can expect to see a new draft guidance reflecting not only updates to technology over the last 10 years, but the clinical research industry’s commitment to finding out how patients feel and function, not just looking at additional life years.What do you think the future looks like?Although BYOD isn’t a new idea, the perspectives on it are evolving industry-wide. In the case of ERT, we typically provision devices, but are leading the way by providing multiple avenues to collect patient reported outcomes, including provisioned devices, web portals, and cell phone apps on the patient’s own devices. It’s clear that this method of data collection is now acceptable in the industry. The most interesting aspect is a new trend of multi-modal data collection. This presents some new challenges, but the industry is poised to overcome them and ultimately making it easier for patients to participate in clinical trials.

What have you seen and experienced in cardiac safety in 2019?Cardiac safety is typically seen as a very stable area. However, in 2019, there was a lot of evolution as sponsors began to look for ways to reduce patient burden and find real-world cardiac evidence. Enter wearables: advancements in these convenient devices have made it possible to track patients’ health and the safety and efficacy of therapies at home, as in Stanford Medicine’s Apple Heart Study. This trend also reflects the shift toward home-based monitoring, which was reflected in the FDA’s new guidance on ABPM.What do you anticipate happening in the industry in 2020 and beyond?It’s become clear that passive health monitoring is the future of clinical trials. Technology will allow sponsors to collect data while the patient goes about their everyday lives, without requiring them to remember to wear or charge a device, even one they already use. Advancements in science and technology are making it possible to monitoring patient health at home in ways that are increasingly less intrusive, deviceless, and home-based. These developments will continue beyond 2020. In the next year, we also anticipate a huge shift toward virtual trials, and the evolution of wearables as they become less exploratory and instead primary and secondary endpoints in clinical trials.

Introduction [00:50]We welcome Jean-Phillippe Couderc from VPG Medical as he joins Trial Better to discuss passive health monitoring and VPG Medical’s technology, HealthKam.What is passive health monitoring? [02:02]Passive health monitoring, or opportunistic monitoring, embeds sensors that measure data into technologies or devices that are already used by the patient in everyday life, like smartphones, bath mats, and toilet seats. These devices place minimal constraints on the patient whereas with typical home or remote monitoring technology, patients are required to take care of the device. For example, a patient using an Apple Watch still has to charge the device and remember to wear it every day. Passive monitoring addresses this challenge.What are some of the challenges of passive health monitoring?[04:25]Since passive monitoring technologies don’t disrupt the patient’s lifestyle or require any behavioral changes, you need to ensure the sensors will be used consistently in other ways. This requires identification of devices that the patient naturally uses on a daily basis, which may change based on certain demographics or the patient’s routine.How do we ensure high-quality data from opportunistic monitoring?[06:50]With regular monitoring, you have more reliable, good quality data (for example, measurements from an ECG electrode making direct contact with the skin.) However, these methods also have shorter monitoring periods with physical constraints. ECG patches can only be used for up to 15 days because the connection between the skin and electrode loses viability.With passive monitoring, the sensor is far from the patient, so external factors have more of an impact and you have less control over the data quality. However, artificial intelligence algorithms can be used to identify which data is actually valuable. Because passive health monitoring constantly collects data, you have hundreds of measurements; even if 50% of the measurements aren’t usable, you still have enough valid data.How do patients feel about privacy with passive data collection? [09:03]Technology today is designed so the patient’s information can be kept private, and there are solutions to avoid sharing PHI. For example, data can be encrypted, or technologies can be designed to collect only information related to the study (and not the patient’s name, address, etc.) Data privacy is changing, and the relationship consumers have with their data is, as well; patients are more comfortable with sharing their data than ever before. In some cases, patients who are terminally ill may be willing to sacrifice their privacy because the potential value of the information collected outweighs their concerns.What is HealthKam? [11:45]HealthKam uses the cameras embedded into smart devices to monitor your face and extract information about your pulse. As the quality of these cameras has increased, it has paved the way for passive health monitoring solutions like HealthKam. Each time your heart beats, it effects your blood pressure and causes a subtle change in the color of your facial skin. HealthKam’s unique technology detects these changes and extracts the person’s heart rate without touching them.How does HealthKam work? [14:16]HealthKam uses facial recognition to identify the patient, and then passively runs in the background while the patient uses their device. This technology isn’t restricted to smartphones (which patients may only use for short periods of time), but other devices like tablets, which may be used for longer periods, such as the duration of a movie or TV episode.How will passive health monitoring impact the clinical research industry?[17:00]Most arguments focus on the burden micropayments can put on sites. It’s yet another technology that sites have to engage in, and it can be difficult to go through the set-up process and train staff. However, sponsors need to consider these things not just with micropayments, but all with technology, so it’s important to take a step back and determine if micropayments can provide a benefit to the trial.

What is a micropayment? [02:16]Micropayments are a small financial transaction. The threshold for what is considered a micropayment can vary based on industry, geographic location, and other factors. In clinical research, micropayments can influence and encourage patients to take complete any actions outside of a clinical visit that may be necessary.Why are micropayments a hot topic right now? [02:58]The clinical research space has reached an inflection point. Previously, there was resistance to methods that may have been considered coercive. Now, new FDA guidance has clarified how patients can receive compensation for their participation in clinical trials. There’s an overall industry-wide shift toward being patient focused and recognizing the sacrifices patients make to participate in a clinical trial, as well as making that participation more convenient.What’s the level of sponsor interest in this type of technology? [04:15]Sponsor interest in the use of micropayments is growing, along with recognition that sponsors who use micropayments can still engage with sites efficiently. Many sponsors are interested in being the “sponsor of choice”; sites want to be the “site of choice.” How can sponsors engage better with sites efficiently? That’s where this type of technology can come in.How can sponsors address concerns of coerciveness if they’re interested in using this type of technology? [05:27]There will always be a balance in the industry between innovating and remaining compliant with regulations and guidance. Vendors like Greenphire can provide consultation regarding this. With micropayments specifically, coercive compensation isn’t a concern - small amounts (>$10) simply encourage patients to continue to comply with protocol and what they’ve already agreed to as patients. Regulatory bodies are starting to see that and are generally supportive of that.How can micropayments be used in specific therapeutic areas? [06:33]Micropayments can be used in a variety of therapeutic areas, but are particularly effective in therapeutic areas where diary entries or measurements taken outside of a clinic visit are required, such as in diabetes or Parkinson’s disease. The payment serves as a reminder, encouragement, and “thank you” for the patient’s trial participation. The potential for micropayment uses cases is vast, but they tend to work best when patients need to be engaged in and mindful of their condition and report data outside of a site visit.Are there measures other than completing a daily diary where micropayments can have an impact? [08:01]Diaries are a common use case, but anything like ePROS (patient reported outcomes) are an opportunity for micropayments. It’s important to consider protocol design and address the site perspective - since the site will need to engage in the technology with the patient - as well as any other technology that will be used in the trial, to ensure that each piece of technology can communicate with the other.What are the arguments against using micropayments? [10:23]Most arguments focus on the burden micropayments can put on sites. It’s yet another technology that sites have to engage in, and it can be difficult to go through the set-up process and train staff. However, sponsors need to consider these things not just with micropayments, but all with technology, so it’s important to take a step back and determine if micropayments can provide a benefit to the trial.How can you measure the effectiveness of micropayments? [12:10]Multiple studies revealed that micropayments have the biggest impact on patient retention. With more complex protocols, finding the right patient can be like finding a needle in a haystack. Encouraging patients along the way helps ensure they aren’t dropping out of the study and can remind them why they chose to enroll in a clinical trial in the first place.Where do micropayments fall in the future clinical trial landscape? [13:12]Any time you’re engaging in a clinical trial, you have to consider the full spectrum of stakeholders engaging with technology and how it will impact them: ease for patients, efficiency for sites, and transparency at the sponsor or CRO level. It’s important to look toward the future in the industry and continue to recognize and thank patients for participating in the clinical trial as we move toward decentralized or digital trials.

Introduction [00:42]Learn about best practices for patient recruitment, one of the biggest concerns in the clinical trial industry. We’ll discuss the importance of precision recruitment and site-follow up, as well as patient recruitment challenges like diagnosis, eligibility and diversity.What’s the number one problem with clinical trials? [03:03]The number one problem with clinical trials is speed. Research isn’t happening as quickly as it should, and patients are waiting too long for new and better treatments while sponsors are spending too much money and time. The most effective way to address this problem is smart and efficient patient recruitment strategies.What’s the importance of patient recruitment? [03:45]There’s a gap between what patients need and the ability of clinical research to address these needs. About 80% of clinical trials are delayed or stopped due to enrollment issues, meaning that the drugs take longer to get to market or they never get there at all. Some disease prognoses are shorter than the average amount of time it takes for new drugs to get to market, which is 10 years. These patient stories illustrate the necessities of fixing the issues with patient recruitment from the patient side..Why does this gap exist? What are some factors that make a study difficult to recruit patients? [04:40]There are a number of different factors, such as complex protocols with increased eligibility criteria, making trials harder to recruit for. Additionally, there’s a lack of patient awareness around clinical trials. They don’t hear about trials because doctors rarely bring them up, or they have the misconception that trials are only for people with no other options. Education about clinical trials is crucial to improving patient recruitment efforts.How do complex protocols effect patient enrollment? Are these trial design problems, or just ones that require a specific approach to recruitment? [06:06]The increased complexity of protocols mirrors the increased complexity in the science of the drugs being tested. As medications become more targeted, especially in therapeutic areas like oncology, it has become more difficult to find patients who can participate in clinical trials. Precision recruitment techniques, with very targeted patient outreach, are more effective at finding patients who meet specific trial criteria.How has the role of the patient changed in the recruitment landscape? [08:31]Patients are becoming their own advocates by doing research on their dignoses, joining patient communities, and actively looking for treatment options. When running patient recruitment, it’s important to understand the voice of the patient to communicate and engage with them where they’ll be most receptive.How can other clinical trial stakeholders reduce site burden through patient recruitment? [09:42]In the future, the ability to measure various aspects of airway function will improve due to the shift towards personalized medicine, with new methods regulated and approved by the FDA.What might sponsors be surprised to learn about digital patient recruitment technology in clinical trials? [11:39]There’s been a slow adoption process for digital patient recruitment technologies, mostly due to the changes it can require to a sponsor’s internal processes. The industry is still relying on traditional advertising tactics for recruitment, but the digital world has untapped potential. Almost everyone is online or using a smartphone, including the aging population which is more tech savvy than it ever has been before.How can patient recruitment address the issue of diversity in clinical trials?  [14:50]In June 2019, the FDA issued draft guidance on the importance of increasing diversity in clinical trial populations. It’s often incorrectly thought that communities of color are not interested in taking part in medical research. However, research teams and recruitment companies need to cater their outreach in a way that contextualizes clinical trial opportunities, addresses historical concerns, and gives people the information they need to feel confident about volunteering for clinical research.The patient recruitment market is expected to continue to grow into 2020. Where is it headed and how will it continue to evolve clinical trials? [18:10]Increased patient awareness about their health decisions and data will shape and impact many industries, including patient recruitment.

Introduction [00:20]Phil Lake and Dr. Kai Michael-Beeh examine the steps sponsors and study teams can take to improve data quality and reduce data variability in respiratory trials. They also discuss the innovations and trends they expect to see in the industry in the future.How can sponsors and the pharma industry overcome unacceptable data variability from sites? [03:30]Respiratory measurements can be complicated and challenging if study teams don’t stick to the fundamentals. This means that variability and bad data quality are common issues. Two major factors can contribute to variability: disease-associated factors and effort-dependent factors. Both of these issues can be managed, with strict standardization in the protocol and rigorous training, respectively.Is a focus on ATS/ERS standards enough to generate research-grade data? [06:34]ATS/ERS standards are a suitable starting point and principle for quality assurance. However, simply applying these rules is not sufficient. In addition to following these standards, sponsors should implement additional visual inspections and plausibility checks.How can we use available technology and services to reduce data variability? [09:50]Available technology and data should be used to guarantee the production of the highest quality data possible. Ensure that investigators are aware of what defines a good quality test in the context of a clinical trial, including how important it is to show changes in lung function. Increased overall communication with investigators decreases variability, as well as the number of patients needed (and ultimately costs.)How can sponsors and sites best stay on track with projected timelines? [14:35]Communicating with sites so they can more effectively allocate their resources, especially when a study has fallen behind, can be a crucial improvement. Checks should take place to ensure that third-party providers are ready to begin once the site is initiated.What’s the real cost or impact to pharma when we produce variable data or run into study delays? [19:18]Variable data and study delays have a tremendous impact by putting approvals at risk and jeopardizing the reputation of the drug or manufacturer. When studies produce better data, there’s an increased chance of achieving study goals with less patients and lower costs. Better data also improves confidence in negative results.Any future innovations that will improve data quality? How can we do better as an industry to understanding drug effect? [21:38]In the future, the ability to measure various aspects of airway function will improve due to the shift towards personalized medicine, with new methods regulated and approved by the FDA.

Introduction [00:45]Ken Faulkner and Katarina Krosback explore the potential benefits and pitfalls of Bring Your Own Device (BYOD) in eCOA clinical trials, as well as the current regulatory perspective. In this episode we discuss the future hold of BYOD, the value of patients using their own devices and the technology needed for BYOD trials.What does “BYOD” mean in the context of a clinical trial? [03:33]In BYOD, or bring your own device, the patient uses their own cell phone to complete their reports. This simplifies the process for patients, who are already very familiar with using their cell phones to complete a number of tasks, and makes it easier for them to remember to participate. BYOD has not yet extended to devices other than cell phones.What are the benefits of a BYOD trial? [05:05]There are two main benefits of BYOD: familiarity and simplicity. Because patients are already familiar with the device and carry it around constantly, it’s much easier to encourage them to be compliant. BYOD is typically app-based, something most patients will know how to navigate.What are some of the potential pitfalls of BYOD?[6:22]It’s important to note that there are many factors that need to be considered in order to successfully implement BYOD, including complexity, frequency of recordings, data volume, and patient location. These factors, and others, can have a large impact on a study’s budget. Additionally, sponsors should have a back-up phone provision plan in case patients don’t want to use their own devices.Has the volume of phone options available been a pitfall in implementing BYOD?[09:24]Although there are a number of devices available on the market, most patients generally have one of a few different types of phones and/or software. This has made implementing BYOD a simpler process. However, the app’s compatibility with a number of systems should be assessed before moving ahead with BYOD in a study.What’s the currently regulatory perspective on BYOD?[10:21]Because BYOD is a fairly new concept, regulatory bodies have not yet formed a final opinion on its use in clinical trials. However, regardless of what device is used or how data is collected, a trial that uses BYOD must also adhere to all existing regulations, just like any other trial. Experts anticipate that there may be more regulatory oversight on BYOD in studies where PROs are a primary efficacy endpoint.What impact will BYOD have on the industry?[11:29]BYOD is not a shortcut, but rather a simpler approach to collecting data in a trial. Sponsors and study teams will still need to follow their typical set-up and training processes. Industry-wide discussions will need to take place, however, in order to address BYOD’s impact.What’s the future of BYOD?[12:54]BYOD is here to stay, but it should only be implemented in a trial after the cost and benefit aspects have been evaluated. Sponsors need to ensure that they’re choosing the right trials in order to use BYOD effectively. Advances in technology may also make BYOD more effective in the future. An ongoing dialogue with regulatory bodies as these changes unfold will be necessary.

Patricia Castellano and Emily Olsson explore how sites can benefit from developing a stronger relationship with their ABPM device vendors. They also address strategies for successful repeat ABPM sessions when a patient is non-compliant, and how ABPM achieves a type of holistic data not possible with other BP measurement methods. Introduction [00:37] Patricia Castellano, Senior Director of Product Management at ERT, is joined by Emily Olsson, CCRP, from the University of North Carolina Chapel Hill for an in-depth look at the keys to implementing a successful ABPM protocol in a cardiac safety trial. Improving ABPM through Better Site/Vendor Relationships [04:10] Sites that don’t have much experience with ABPM shouldn’t hesitate to reach out to device manufacturers to ask for training or assistance when needed. Other external teams and experts may also be willing to provide ABPM insights. Vendors who can provide customizable software with easy-to-read outputs are ideal. Achieving Successful ABPM Repeat Sessions [07:37] If a patient is non-compliant or produces unusable data, a repeat ABPM session may need to be scheduled. Discuss the outcome of the original session with the patient and identify how the experience can be improved. Proactively manage the expectations of individuals in patient groups that may experience repeat inflations – such as elderly or obese patients – and provide them with tips and tricks that can help improve their comfort and compliance. Using Home Blood Pressure Monitoring (HBPM) Instead of ABPM Comparing Compliance with ABPM to Other Blood Pressure Monitoring Methods [12:01] Home blood pressure monitoring provides more comprehensive blood pressure data than a single measurement in the clinic. However, patients are typically not well-educated on how to use a home blood pressure device and may fall out of compliance over the duration of the collection period. This results in data that isn’t a true reflection of their blood pressure.

Introduction [00:31] Patricia Castellano, Senior Director of Product Management at ERT, is joined by Emily Olsson, CCRP, from the University of North Carolina Chapel Hill for an in-depth look at the keys to implementing a successful ABPM protocol in a cardiac safety tril. Enhancing Data Quality and Value with Hands-On Training [2:31] Hands-on training provides benefits to both patients and site staff. Participants who receive training feel more engaged in the ABPM data collection process and are more likely to be compliant. Site coordinators who wear the ABPM cuff as part of their training develop a deeper understanding of the device and can better relate to and communicate with patients. A focus on training improves data quality and, ultimately, usability in clinical and medical applications. Improving ABPM Patient Compliance [04:21] Participant preparation can help sites achieve higher patient compliance rates. Standardized instruction sheets and troubleshooting tips and tricks can increase trust between the patient and the site coordinator, and empower patients in their ABPM experiences. Coordinators should set realistic expectations about ABPM and how it can be uncomfortable and intrusive, and be available to patients who have questions about ABPM or their device. A transparent relationship between the patient and the site coordinator is critical to compliance. Successfully Implementing ABPM [09:09] Successfully implementing ABPM requires training, experience (or a willingness to ask questions), and buy-in from both sites and participants. An important initial step is to gain an understanding of the patient experience by wearing the ABPM device. Schedule internal meetings on a regular basis to identify trends and issues that can be improved with better site or patient education.

Drew Bustos, Senior Director of Business Intelligence Products, is joined by Dr. Santikary, Vice President and Global Chief Data Officer at ERT, for a discussion of the role of modern data architecture. Clinical trial sponsors and CROs are facing increasing numbers of complex data integration and quality challenges. Are you struggling to keep up with this exponential data growth? The solution may lie in modern data platform, cloud, and artificial intelligence technologies. Data Architecture Challenges in Clinical Trials & Healthcare Data architecture challenges can be significant, and often include data security; data privacy and protection at scale; data integration at scale; real time reporting and analytics at scale; and data governance and master data management at scale. A modern data platform can be built to handle these challenges. Common Data Integration Problems Integrating data and serving it to the end user in one, centralized location is easier said than done. Different vendors and technologies, using disparate platforms, make the integration process even more difficult. In addition to a lack of standardization, unstructured data and binary data further compound the data integration and architecture challenges. Emerging Trends in Data Architecture and Technologies in the Clinical Trial and Healthcare Industries The rate of change in clinical research and healthcare technology is unprecedented. In particular, artificial intelligence and blockchain technology are making a huge impact in clinical research. The State of Artificial Intelligence and its Clinical Trial Application Sponsors and CROs can expect to see a major shift toward embracing AI in the pharma industry over the next few years. In fact, this trend has already begun with the use of predictive algorithms, chatbots, and voicebots in clinical trials. Artificial intelligence has the potential to accelerate drug discovery and increase trial efficiency.

Introduction Vivienne de Walle, Co-Founder of PT&R - a dedicated clinical trial site in the Netherlands, is joined by Chris Porter, VP of Marketing & Digital Strategy, ERT for a discussion about the importance of involving clinical sites in the design of clinical studies. Sites are on the frontline of your clinical trials and as such, bring with them a wealth of experience and advice on how to make trials run more smoothly and efficiently, ultimately bringing drugs to market faster. Here’s a summary of what you can expect from the podcast: The value of your sites embracing technology Paper data collection is still used in clinical studies. Learn how a site views the importance of embracing technology to get drugs to the patients who need them, faster. Simplify site staff’s day-to-day lives Keeping sites engaged in clinical trials is vital. If sites are motivated, they will be high recruiters, help achieve high compliance rates amongst patients and give you the data you need to make your trial a success. To do this, we need to make taking part as simple as possible. Eliminate multiple portals with multiple logins, ensure automatic notifications to site staff are part of the protocol to capture patients who are non compliant and ensure training requirements are kept to a minimum. Involve sites early in your study design Sites spot problems which sponsors, CRO’s and vendors may miss. For example, is the device actually intuitive to use? If not, patients are likely to be non-compliant. Asking patients with specific neurological conditions to use a stylus to record electronic diary entries may prove problematic and might result in the failure of the entire trial. These kinds of details may be overlooked by anyone but the site, yet are vital for the success of the trial itself.

Introduction Brett Hoover, Product Management team lead for ERT’s imaging product line, is joined by Amit Vasanji, Chief Technology Officer of imaging at ERT, for a look at imaging trends, strategies, and best practices in the clinical trial industry. How can using imaging effectively reduce cost? What impact will innovative imaging approaches have on a trial? What do sponsors need to know in order to maximize the benefits of imaging? The Growth of Imaging in Clinical Trials Over the last ten years, more advanced technologies have enabled imaging to shift from a qualitative to quantitative practice. Automated imaging analysis can reduce costs and provide consistent, objective data, improving patient safety and treatment efficacy. These developments, among others, have made imaging data more valuable to regulators and other audiences, including patients, payers and providers. The expectation for high-quality imaging data as part of a trial is more prevalent than ever before. Best Practices for Using Imaging in Clinical Trials It isn’t possible to maximize the implementation of imaging in a clinical trial by waiting until the last minute. Case studies that demonstrate a successful use of imaging make apparent the importance of two things: planning and equipment auditing. Waiting to address imaging requirements or audit imaging equipment available at study sites are two common missteps. Finding the Right Imaging Partner In order to ensure they’re using the most innovative, effective imaging techniques, sponsors and CROs should partner with an organization that offers a deep understanding of how to work with imaging technologies to develop custom protocols. Flexibility and creativity lead to effective imaging partnerships that reduce costs and provide accurate data on time.

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