Jason Weatherald, MD - phaware® interview 524

Beyond the Clinical Trial: What Real-World Data Means for You.

Think only people in clinical trials help advance medicine? Think again. Dr. Jason Weatherald explains how your everyday clinic visits - from walk tests to how you feel - can help shape the future of pulmonary hypertension treatment. Learn what "real-world evidence" is and why your story matters more than you think.

I'm Jason Weatherald, I'm from the University of Alberta in Edmonton in Canada. I'm a clinical researcher, I focus on pulmonary hypertension and also on lung transplantation in my practice. I do a lot of research related to patient-oriented ideas and clinical trials.

Today I want to talk a little bit about real-world data and real-world evidence and what that means, and why it's relevant in pulmonary hypertension.

Real-world data and real-world evidence are related to complementing clinical trials. The way that new treatments get to the marketplace for any disease is through randomized controlled trials. These have to be approved by regulatory bodies, like for instance, the FDA in the United States, or the EMA in Europe. Clinical trials are different than what happens in the real world. When you're running a clinical trial to get a new treatment approved, you want your trial to be successful. The trial has very strict criteria on what type of people can be in it, and they have very strict measurement, and it's very tightly regulated. That's important and that's really good. That's how we know things work under ideal circumstances.

However, when a treatment is approved and it starts getting used in the real world, the types of patients that are on a drug or on a device are always different than what's in the clinical trial. We call that real-world populations. So, we also need data and evidence from real-world populations as to how a treatment is actually working in practice. Because the selection criteria for a clinical trial are so narrow and so tight, the results are not always generalizable to the everyday patient in front of you who may be older, who may have other comorbid conditions. They may have a bit of kidney failure, they may be overweight, and sometimes clinical trials don't include those people. So we need other sources of knowing that a drug is safe and also likely to work in the broader population.

We call that real-world data. The information that we get from real-world data becomes real-world evidence. That's the type of evidence that we can use to make decisions in clinical practice. Patient reported outcomes can still be used in a clinical trial. Those are any sort of description of how a patient's feeling or their quality of life. It's just what the patients are telling you is going on that can be used in a clinical trial.

There are other types of real-world data. I'll give a few examples of what we're talking about with real-world data. After a drug is approved, now most of the regulatory bodies require companies to perform drug registries. These are basically people who are on the drug in the real world and they're collecting information about side effects, because they can look at much larger populations of people who are taking a drug. Maybe rare side effects didn't show up in a clinical trial because there's only 300 or 400 people in the trial. But what happens when 5,000 people are on a drug? So drug registries are one type of real-world data.

There's also really powerful other sources that are collected in everyday practice. When you go to the hospital, you might have an electronic medical record, and then physicians and surgeons apply billing codes for all of the services that they provide. That data go to massive databases. So for instance, in the US, the Veterans Affairs has this massive database of people that have sought care, and you can also obtain data from those sources. We call them administrative databases. They may have tens of thousands of patients. You can look at associations and you can try to understand rare side effects or health resource use in the real-world population. So those can be a great source.

Patient biometric data is one potential source of real-world data in the future. So you could think about a watch or a Fitbit or an Apple device collecting patients' real-world data on what's happening to them with their step counts, their heart rate in the real world. That is one other potential source that we really haven't capitalized on quite yet in the pulmonary hypertension world. But this has been used in clinical trials already, and it has been used in real-world studies in other diseases in the cardiovascular arena. I think this is one potential area, and you could even consider integrating things like your step count, your heart rate, and your patient-reported outcomes like how do you feel on a given day, multiple days in a month? Using emerging, very sophisticated computer and artificial intelligence approaches, you can get a better picture of how someone's doing day to day from that type of data that might be much more powerful than what we're collecting in clinic visits that are every three or four months apart. Those are just snapshots, and that type of real-world data is more like a videotape. It tells you what's going on all the time.

For instance, like administrative databases. I've worked with this in my own healthcare region, and it's all de-identified, it's associated with numbers that could be identified. But when you get the data from, for instance, your health region or your hospital, it has all the identifiers taken out. But it may have things like age, and sex, and sort of how many comorbidities a patient has. The administrative data is de-identified, and it may be under the jurisdiction of a hospital or in Canada where I live in a province, but the drug registries are different. Participants would only get their data into that type of a setting through a normal informed consent process. They would have to sign a consent form to have their data collected. Of course, it is always under the protection of the physicians that are running those studies, and the anonymity and confidentiality of that data is the responsibility of those doctors. None of that identifiable information should be shared with the companies that are asked to run these studies. But it really depends on the setting.

One of the things I hear from patients all the time is that they want to participate in research, but maybe they don't want to be in a clinical trial or maybe they don't qualify for clinical trials. This is a way that patients can participate and there's really nothing else that's asked of them. Usually, these drug registries are done as part of routine care. We're only sharing information like, how does a patient feel? What was their walk test? What was their blood test that day? If they have a heart catheterization, what are those numbers? It's a way that patients can feel that they're contributing to knowledge without having to do a bunch of extra things. For many people that's enough. They feel like they're altruistic in some senses, it's people helping the generation of knowledge in a way that they can.

The other benefits I think are so that we do learn, how safe are these new treatments? How well do they work in the real world? As researchers, we can ask scientific questions that we can look at the data once it's accumulated over many years to say like, "Well, have you thought about this?" So we can even go to the companies and say, "Well, you should look at this. We're seeing this in the real world. Maybe you should make sure that this isn't the problem." For instance, risks of bleeding or risks of headaches. We might be seeing stuff that wasn't necessarily picked up in a clinical trial, and that can be a red flag that makes us do things differently to protect the safety of patients.

There are lots of opportunities to tell patients about different ways they can be involved in research. It really does depend on the individual patient. For instance, at my university, we may be running five or six clinical trials at once, and the criteria for them are different. So we have a cheat sheet and we look at the patient. We always ask them, first of all, "Are you interested in participating?" If not, then the conversation ends there. But if patients are interested and they want to hear more, we do have to spend a bit of time looking at what they would qualify for.

For instance, some of these drug registries are only applicable for people who are about to start a new drug. So they're starting drug A, and there's a registry for drug A. It doesn't mean that I would put them in the registry for drug B. So those opportunities only come out often when people are starting new treatments, so they may be few and far between.

In terms of clinical trials, it's something I bring up almost every visit and just say like, "Hey, these are the opportunities. Do you want to participate?" If not, we end it there. But people change over time, they might not be eligible for a clinical trial at this visit, but maybe in six months they are because things have changed, or maybe they're not on a certain drug that's excluded, or maybe they're a bit worse and now they qualify for clinical trials.

It always adds extra time to the visits, but it's important, I think. One thing I always say is that all of the treatments we have now are only here because of people who participated in trials in the past. Some of those people are no longer with us. That's their legacy, That's the gift of knowledge that they gave to the future generation of people with PH is we learned what works and what doesn't work because of people that participated in trials. I think that's important that people understand that, and acknowledging that it's still not right for everybody to participate in a clinical trial. But what I like about the real world data is that that's just a great example of how people can contribute in other ways.

There's other registries. A lot of countries have national registries where patients can sign up. Again, we just collect data from each visit as people come through the clinic, it's just reflecting what happens in the real world, and that's where the name comes from.

I'm Dr. Jason Weatherald, and I'm aware that my patients are rare.

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