Aug 8, 2017
Dr. Peter Leary is a specialist in pulmonary and critical care medicine who cares for patients with pulmonary hypertension. Dr. Leary is focused on clinical care and research for patients with pulmonary vascular disease. In Part 2 of his 3 Episode series on Clinical Trials, Dr. Leary discusses the role of placebos and built in patient safety checks in clinical research studies in the fight against rare disease.
I'm Peter Leary. I'm a pulmonary hypertension physician in Seattle, Washington. I work for the University of Washington as part of the University of Washington Pulmonary Vascular Disease Program, and have been there since about 2009.
So today I'm going to go a little bit deeper into talking about clinical trials and some of the nuances of that conversation.
If you were in a trial, you were getting placebo, or you were getting active drug, you don't know what you're getting during the study. At the end of that initial phase of the study, if it looks like there was a benefit to it, then you have the opportunity to kind of go into this open label extension, which means you're going to know what you're getting. You know that you're getting drug at that point. You still may not know whether you were getting drug or placebo during the original trial, but you will know that you're getting drug in the follow up trial.
Essentially, this is a way, as you're trying to understand more about a drug, to take it to a bigger group of people, follow them over time, and one, continue to make sure that it's safe, there's not a safety concern that we've missed, and also to make sure that it's effective in a larger group of people. There isn't always an open label extension. Sometimes a trial will end. But the majority of the time, there an open label extension. If and when they do end, it typically means that they think that it's going to be commercially available in very little time, and people can be prescribed it in the normal course of clinical care.
I'm sure everyone has had the experience of opening up a new pill and reading the package insert that has the list of every side effect known to mankind. And the reason that happens is when you're doing a trial, anything that happens to you while you're on that drug is collected. You get in a car accident, you get a runny nose, you get hit in the face with a baseball. If you mention it to your study team, that is something that is collected as an adverse event. As you're going through and doing these intermediate checks, one of those intermediate checks is to say, "Okay, for all of these more common adverse events, sinus infections, colds, bruising, things like that. Is this happening more often in the group that got the drug than the group that got placebo?"
If it is, then you say, "Well, there might be a chance that the drug is causing this problem." And so that's one wing of it. The second wing of it is that there are what are called, "Serious adverse events." So, if you get into the hospital, or you have something that is fairly major, beyond the kind of hum drum outpatient world, call your doctor, check in on it, those are reported back to the FDA within a very short time window so that we can pick up on a signal for these serious events much earlier in a trial and stop a trial. Often times, a trial will get stopped and then re-started. There will be some investigation, people will look into these serious adverse events, and at the end of the day, they'll say, "You know what? We really don't think this was related to the drug. We can keep going with the trial."
These safety checks are built strongly into any trial because the last thing anyone wants to do is hurt somebody in the process of trying to help them. It's real life, and so there's a little bit of uncertainty, but there are layers and layers of back up and protocol with the intent of trying to makes sure, to the best extent possible, that we're not doing that and not hurting patients with our drugs. When you look at a trial, and this is one of the critiques that people have of clinical trials, is they are extremely stringent about inclusion and exclusion criteria. If I'm in clinical practice, and I want to give somebody a drug, I often times will say, "Okay, I have a panel of drugs that I think might help you. I'm going to try one and see how it works."
In a clinical trial, the idea is that you want to make the group of patients you're studying look nearly identical to each other. We do this through a series of inclusion and exclusion criteria. So for a drug of a trial of pulmonary arterial hypertension, you would say, "Okay, everyone to be included in the trial must have pulmonary arterial hypertension. But they can't also have problems with heart valves. They can't also have problems with scarring in their lungs. They can't also have X, Y, or Z." And the reason why is that when you get done with that trial, it's either going to show that there was benefit to the drug or there was no benefit to the drug.
And if at the end of the day, you're not sure if the group of patients were exactly the patients that you thought were going to benefit from the drug, and it shows no benefit, you may be abandoning a good drug when in fact it still works. So trials tend to be very, very strict, because they don't want to get to the end of the trial, not have shown a benefit, and say, "Well, you know what? It's because this drug probably doesn't work when people have scar in their lungs. And unfortunately, we got half of our group had scar in their lungs."
And so inclusion exclusion criteria are trying to create that environment where you know exactly what group of people you're studying it in. The challenge for clinicians on the other side is to then say, "A lot of patients don't fit the criteria that were used in the trial. Is it still worth trying this drug for those patients?" That is a very individualized kind of personal clinical treatment decision, and get some of the uncertainty that having these very specific trials generate.
My name is Peter Leary, and I'm aware that I'm rare.
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