Joey Wahler (Host): They test the effectiveness and safety of drugs and other medical treatments. So, we're discussing the basics of clinical research. Our guest, Dr. Viveka Boddipalli. He's a Pulmonary Medicine and Critical Care physician and Senior Vice President, Medical Director of Value-Based care for Duly Health and Care.

This is Duly Noted, a health and care podcast. Thanks for listening. I'm Joey Wahler. Hi there, Dr. Boddipalli. Thanks for joining us.

Dr. Viveka Boddipalli: Hi, Joey. My pleasure.

Host: Great to have you aboard. So first, we've all heard the term, but what exactly, in a nutshell, is clinical research? And why is it so essential?

Dr. Viveka Boddipalli: Yeah. So, clinical research, it really encompasses a lot. But it's ultimately just a study of medical therapies and diagnostics, looking at the safety and efficacy, which commonly involves human subjects, but doesn't always. But what we do here at Duly Health and Care is almost exclusively with patients. And these are super important, crucial, in fact, for advancing medical knowledge. Any of the therapies that you think of now that comprise modern healthcare, from insulin to total joint replacement surgery would not be available without clinical research or wouldn't be available in a safe way for our patients.

Host: Absolutely. And so, that being said, how are clinical trials typically designed and conducted? Who and what's behind all this?

Dr. Viveka Boddipalli: Yeah. So, almost all clinical trials are conducted according to strict ethical and regulatory guidelines designed really to protect participants and ensure the validity of the results. They're generally designed by a primary investigator or scientist looking to answer a question alongside a sponsor, and that sponsor can be anybody from a pharmaceutical company to a non-profit institute, such as a hospital or a healthcare system like Duly, or a government entity through a grant.

And so, once a researcher decides on what they're looking to study, they create a design, such as a randomized control trial to outline objectives, methodology, and eligibility criteria. And then, that in turn undergoes a very rigorous ethical and regulatory review, usually by a body called an IRB or an Institutional Review Board. And that's meant to ensure a third-party objective view to ensure legal standards are met; participant safety, rights, and privacy are maintained.

Host: Gotcha. Now, we typically hear of clinical trials being conducted in phases. What are usually the phases that make up one?

Dr. Viveka Boddipalli: Now, so broadly, these trials generally follow a sequence from small phase I trials all the way through to larger phase III studies with each phase building on the knowledge gained from the previous one. Phase I trials generally shorter in duration involving anywhere from 20 to 100 patients. And these really just look at dosage ranges and how a drug interacts with the body, something called pharmacokinetics, essentially how the drug is processed and eliminated from the body.

Then, phase II trials involve a few hundred patients, again, building on phase I, looking at optimal dosage and continuing to monitor for side effects. And then, you get to phase III trials, which is really answering the crux of the question around how effective is this intervention that they're looking to solve for, and this again builds on phase I and II, often involving thousands of patients over years.

And then, what's often overlooked are what are called phase IV studies. These are essentially post-market safety monitoring, which occurs after a drug has been approved or a device has been approved by the FDA. Now, not all interventions make it through all phases. Many fail due to lack of efficacy and safety. And in fact, most don't make it all the way through to phase III. And I think the FDA estimates about only about a third of drugs move from that phase II to phase III with another only 25-30% making it past phase III.

So, I guess if we were to look at that a little bit closer, if we have 100 drugs starting this process, only 70 will make it out of phase I. And then, 33% of that or 23 drugs will make it through to phase II. And then, just under six drugs will move out from phase III into that phase IV post-marketing monitoring program.

Host: How about placebos? For those listening that may not know what a placebo is, if you could explain please? And then, what role do those play in clinical research and how are they ethically justified?

Dr. Viveka Boddipalli: Placebos are an incredibly important part of research. And to just define what they are, it's essentially any agent that's designed to seem like it's a treatment, but actually has no therapeutic value. Things like a sugar pill or an inert injection or a sham procedure, and these are used to test the efficacy of a medical treatment versus no treatment. And the use of placebos are really guided by ethical principles that are permitted in generally four cases. One where there is no proven effective treatment for the condition under study. And so, this is something like, say, an Alzheimer dementia medication. There's no current generally approved treatment for Alzheimer's dementia. If somebody were to come up with a new medication to treat that, a placebo would be considered essentially standard of care.

Second, when withholding treatment poses negligible risks to the person. Here, you can think of a trial, say, for male pattern baldness, where withholding any treatment wouldn't necessarily cause harm to the patient. And number three is when there are compelling methodologic reasons for using a placebo and withholding treatment does not pose a risk of harm to the patients. And here, you would think of, say, a new treatment for psoriatic arthritis.

And then, finally, when there's compelling methodologic reasons for using a placebo and then the trial doesn't require patients to forego standard of care therapy. So here, you want to think of, say, a trial of a new drug versus placebo added to the standard of care for chemotherapy for lung cancer. So, we're not withholding treatment, but the add-on therapy is either a placebo or the trial. And what this does is it allows for a rigorous understanding of the investigational treatment safety and efficacy profile when measured against the standard of care while minimizing bias and allowing for objectively valid and reliable trial results.

Host: Switching gears a bit, what would you say is the biggest way in recent years in which technology has influenced the conduct and the outcomes of clinical research?

Dr. Viveka Boddipalli: It's been incredible. It had a significant impact on clinical research from how and where data is collected, all the way through to how the data is actually analyzed across large data sets and allowing for innovative insights. So, one area in particular to highlight would be virtual or decentralized trials that are performed either entirely online or, remotely, patients are monitoring themselves at home. That data is getting sent in to the research coordinators who then are able to interpret that data. It produces geographic barriers and allows for a market increase in diversity of trials. And then, those trials, the output that they publish are then more reflective of our population as a whole. And it's been incredible in terms of the data that's been able to be gleaned from there.

Host: How about examples, and I'm sure there are many, of successful clinical research initiatives that have led to significant advancements in healthcare? Do you have one or two that stand out most in your mind?

Dr. Viveka Boddipalli: Oh, yeah. I think, for most physicians, the Framingham Heart Study comes first to mind, initially started way back in 1948, but this was really so comprehensive. It changed how we understand heart health and led to substantial reductions in cardiovascular mortality rates through preventive measures primarily and through some treatments.

Other areas that come to mind are particularly in the oncology space. The Cancer Genome Atlas started in 2005, analyzing tumor samples from thousands of patients, allowing for personalized cancer therapies that we see now that target specific biomarkers for personalized treatment approaches revolutionize cancer care.

Host: So, having given us a great framework so far, what types of clinical trials does Duly take part in?

Dr. Viveka Boddipalli: Yes. So, Duly participates almost exclusively in phase III clinical trials. We're in approximately 15 therapeutic or specialty areas, all the way from Internal Medicine to Urologic Oncology, from vaccine trials to therapeutic diabetic medications all the way through to operative interventions.

Host: And so, where are the clinical trials conducted at Duly and what types of services are usually included or covered in them?

Dr. Viveka Boddipalli: Clinical trials are conducted throughout Duly's geography, depending on where our primary investigators are and which trial we're looking at. But if somebody is interested in a clinical trial, they can contact their physician who will alert them to what trials they may be eligible for. But there really is no limitation into what trials our physicians are able to participate in.

Host: And you led me beautifully into my next question or answered it actually, doc, because I was going to ask how someone becomes a candidate. Is it that their provider informs them? And I guess the answer is yes, correct?

Dr. Viveka Boddipalli: Yeah. Many times your physician will let you know of trial options, but it's not commonly the standard of care. Sometimes you may be contacted by our research partners based on your eligibility to see if you'd like to participate in a trial that may be relevant to you. Other times, you may hear of a clinical trial through some notifications that are in our clinics themselves. And alternatively, you may hear of trials from friends, family, and we're always happy to engage in those conversations.

Host: A couple other things. What would you say the future holds for the evolution of clinical research in the coming years?

Dr. Viveka Boddipalli: Clinical trials are evolving at a rapid pace. I think we touched on a little bit of this earlier in terms of decentralized trials. But I think the way these virtual trials and decentralized trials are really becoming more inclusive, they're leading towards more precision medicine, and our ability to really understand more holistically from the data that's being output from the trials through artificial intelligence and machine learning will really advance the field even further.

Finally, digital transformation, like wearables, mobile apps, and remote monitoring tools, really wrap their arms around real life implications of some of our trials that we previously haven't had access to. And then, finally, I think, there is very much a focus on patient-centric outcomes and engagement. And again, that really heavily relies on digital tools and patient experiences in terms of their feedback. So, I think the whole field is really geared towards making our patients' and our communities' lives better.

Host: And speaking of that, in summary here, Doc, let me ask you, finally, what would you say is most challenging or rewarding for you personally about working with clinical research at Duly?

Dr. Viveka Boddipalli: Yeah. I think the most challenging piece is making sure that the research we offer our patients is clinically relevant and applicable to our patients. And I think the most rewarding part is being a part of advancing medicine forward, and providing opportunities to our patients in our communities that they wouldn't otherwise have right here at home.

Host: Well, folks, we trust you're now more familiar with the basics of clinical research, Dr. Viveka Boddipalli. Thanks so much again.

Dr. Viveka Boddipalli: Hey, thanks a lot, Joey.

Host: And for more information, please visit dulyhealthandcare.com. Again, that's dulyhealthandcare.com. Now, if you found this podcast helpful, please share it on your social media. I'm Joey Wahler. And thanks again for listening to Duly Noted, a health and care podcast.