I’m Aware That I’m Rare: Vallerie McLaughlin, MD
Vallerie McLaughlin, MD from Michigan Medicine’s Cardiovascular Center breaks down the different phases of clinical trials in part 1 of her discussion. Dr. McLaughlin is the Director of the Pulmonary Hypertension Program at the University of Michigan in Ann Arbor. She is a Fellow of the American College of Cardiology, American College of Chest Physicians, and American Heart Association (AHA). Dr. McLaughlin has been the Principal Investigator of several major clinical trials of drug therapies for pulmonary arterial hypertension and has published numerous papers in this field. Dr. McLaughlin is an editorial board member of Chest, a Guest Editor for the Journal of the American College of Cardiology, and past Editor-in-Chief of Advances in Pulmonary Hypertension.
I’m Vallerie McLaughlin, a cardiologist at the University of Michigan and my area of expertise is pulmonary hypertension.
Today, I’d like to talk to you about clinical trials.
A clinical trial is an investigation to answer a question as to whether a drug or device or some other maneuver works in a specific disease. Clinical trials are important and necessary to help further the therapies that we have available for many different diseases. The only way to get a drug or device or another intervention approved is to do a clinical trial to demonstrate that the drug works, and is safe for patients.
Clinical Trials can be divided into a number of different phases. Oftentimes, before you even hear about the Phase I clinical trial, there have been what we call preclinical testing, usually in animal models to look at the safety and the proof of concept of the mechanism of action of the drug. Once there is data, preclinical data, we often move into a phase one trial. A Phase I trial is usually a trial in healthy volunteers to get some information about the dosing of a drug, and about the side effects that might be expected with the drug.
A Phase II trial is often called a proof of concept trial. It’s usually a smaller trial in patients with that disease, to get information about how effective the drug is to treat certain parameters of that disease. And again, safety is monitored all the way along. Usually, a drug proceeds into a Phase III trial if it’s effective in Phase II. A Phase III trial is what we call a pivotal trial. It’s usually a larger trial that has a clinically meaningful endpoint that the FDA will accept to approve a drug. And of course, safety is monitored throughout. A Phase III trial is what the sponsor goes to the FDA with to get approval for that agent. And then sometimes, there are Phase IV trials. The drug then has already been demonstrated to be effective in a certain disease, but we might want to study it in other diseases or at other points in the original disease, or with other drugs. And so, Phase IV trials can be lots of different scenarios.
Clinical trials have potential benefits, and they have potential risks for patients. Just by the very nature, a clinical trial is testing an agent that is unproven. And so, there could be side effects that have not yet been discovered that the patient may be exposed to. Sometimes, there’s also risks of procedures that are done as part of a clinical trial, were measuring things during clinical trials. And so, patients may undergo additional procedures that they might not have undergone as part of the standard of care.
Many of our clinical trials are what we call placebo control. That’s our way to tell if the drug is really effective compared to no drug it all. A placebo in a drug trial is often a sugar pill or an inactive pill that the patient takes, so that neither the patient nor the investigator knows if they’re getting the active therapy. Clinical trials often are placebo controlled. So, some of the patients received the act of therapy and some of the patients receive the placebo. Patients are monitored throughout the clinical trial. And many clinical trials have safeguards in them so that if a patient receiving a placebo deteriorates, we can record that and offer the patient other therapy. Some trials also allow patients who were randomized to placebo in the placebo controlled portion to go into what’s called an open label extension and get the active therapy after the placebo controlled portion of the trial.
Patient participation in clinical trials is always voluntary. We want to make sure the patient understands what they’re getting themselves into before they go into the trial. In fact, many of what we call the consent forms for the patient or the subject are 10, 15, 20 pages long and describe the trial in detail. So, hopefully, the patient understands their commitment when they enter into the clinical trial. But again, clinical trial research is always voluntary. And if at some point the patient decides they no longer want to be in the trial, they should discuss that with the study team, and it’s always their option to come out of the clinical trial.
Clinical trials are important for medicine in general, and sometimes patients in particular. There are many reasons a patient might volunteer for a clinical trial. Sometimes a patient might volunteer for a clinical trial because they have a serious disease and they have exhausted all of the currently FDA approved options, and a clinical trial might directly benefit them by giving them a therapy that’s not yet commercially available. There are other patients who may not be in that situation, but may volunteer in a clinical trial for the greater good. Just think about it. All of our patients who are receiving therapies today are receiving those therapies because patients before them participated in clinical trials that led to the approval of those agents. So, some patients may be altruistic and even though they may not personally derive benefit from that clinical trial at that time, they know it could be the opportunity for a drug to be approved that would benefit a patient in the future.
So, open communication with a patient’s physician and study team is really important as one considers clinical trial participation. In patients with rare diseases with limited options, it’s important to ask about clinical trials at most appointments, so that you can learn what options there might be. If a patient decides they might be interested in participating in a clinical trial, it’s very important to get as much information as you can about the trial. Much of the information is described in detail in the subject consent form. That should go over many issues, including the study visits, the procedures that might be done as part of a trial, what the patient’s commitment is. It often involves more frequent visits and tests to the study site. It’s important to also learn about the study medication, what the potential side effects are. By the time of trial gets into human studies, we know a little bit about the side effects of the medication. So, it’s important to understand that.
Many physicians participate in clinical trials as investigators, particularly in rare diseases or complex diseases when we’re always trying to learn. Some of the very experts that provide clinical care to patients also do clinical trials. And so, if oftentimes you can have the same doctor, sometimes that’s considered a conflict and you have to see a different investigator on the study team. So, there may be circumstances in which either case can apply.
I’m Vallerie McLaughlin, and I’m aware that I’m rare.
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