I’m Aware That I’m Rare: Vallerie McLaughlin, MD
Vallerie McLaughlin, MD from Michigan Medicine’s Cardiovascular Center explains the basics of clinical trials in part 2 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. I’m a cardiologist at the University of Michigan and my area of expertise is pulmonary hypertension.
Today, we’ll go a little deeper into clinical trials.
An observational trial is just that, it observes what happens to a patient in a certain condition. Registries, for example, are observational trials. And often times there are Phase IV registries that occur after medications have been approved. If you think about it sometimes a limited number of patients are enrolled in the trials that lead to the FDA approval of the agent but other side effects may pop up once patients are exposed. So registries are a great way to look for those less common side effects. So an observational registry would be a situation in which a patient is prescribed a therapy by their physician that is commercially indicated, and the patient consents to allow their data while on therapy to be obtained for the purpose of the registry. Maybe they’ll pick up a side effect that was not anticipated or learn something else when a large number of patients are exposed to that agent. So, that’s an observational trial.
An interventional clinical trial is a situation where we’re trying to learn about a medication and measure something specific. So the patient is often randomized and there are measurements of some efficacy end point. There are study specific procedures that are done to answer a question. In an observational study there’s often no study specific procedure. We just record what’s happening that’s clinically indicated. The interventional trial has a specific question.
Many clinical trials are placebo controlled. Often the Phase III pivotal trials that are used to get FDA approval of an agent are placebo controlled. But there may be instances where earlier phased trials don’t have placebo control. They may just test different doses of the same agent. Sometimes the Phase IV trials aren’t placebo controlled. Randomization is an important part of clinical trials. What randomization means is that once a study subject consents they are randomized or randomly assigned to a group to either receive placebo or a medication or to receive this dose of medications or that dose of medication. And it’s a way that we can statically assess what the intervention is doing.
So the patient has a very important role in clinical trials. We want patients to participate in clinical trials who are invested in the trial and agree with what is going to happen. That’s part of what we call the consent process. They need to understand what is going to happen in the trial. What the extra visits are. What the risks of the medication are. It’s important for the patient to read that consent thoroughly and agree to participate with what is going to happen.
Many clinical trials are sponsored by companies or government agencies that want a specific question answered. For example, many trials are investigational drugs. So they’re often sponsored by pharmaceutical companies that have been developing this drug for a certain indication. So their role is to often work with a scientific body to put together a protocol, a statistical analysis plan. Basically the plan for the trial. And then provide the resources to do the trial.
A clinical research organization is sometimes involved in clinical trials to help smooth the process. A clinical research organization often serves as the intermediary between the sponsor and the study site. And provides the study site with protocols with the case report forms. They often monitor the site to make sure they’re doing the trial properly. And they help resolve any queries, any questions about data that has been obtained.
So the principle investigator is very important. Is really ultimately responsible for the conduct of the clinical trial at that site. The principle investigator at an institution really takes the responsibility for not only what they do as the investigator but what everyone else does. What the study coordinators do. What the investigational drug services do. They really are the quarterback for the clinical trial at that site. And it’s their responsibility to make sure that the trial is done ethically and in accordance with good clinical practices that are accepted worldwide.
The institutional review board is very important to ensure patient safety. Many institutions have their own institutional review board. There are some contract institutional review boards that different investigators can work with. The institutional review board reviews the study, looks at it primarily with patient safety in mind. They want to make sure that this is a reasonable, safe, ethical study for the patient to participate in. And they want to make sure the patient understands the risk. The institutional review board looks over the consent and really makes sure it is explaining to patient what exactly will happen in that study. So every investigator needs and IRB, institutional review board approval to start a study at their site. And then other things need to be reported to the IRB as well, if there’s a problem, if there’s an adverse event that’s unexpected, that needs to go to the IRB so they can determine if it’s safe to continue exposing patients to the study.
Clinical trials are very regimented and have very strict protocols for what happens. One of the most important criteria or things in the protocol are the entry and exclusion criteria for that trial. Clinical trials often want to answer a specific question in a specific patient population. And the inclusion criteria help define that patient population. It may be patients with a disease that have certain criteria based on how advanced they are, how many years they’ve had the disease, how sick they are, a number of different criteria like that. And then there’s often exclusion criteria as well. We don’t want patients who have too many other comorbidities or something that might limit their life or exposure to drug or obviously an important one, is they’re competent to participate in the trial. So it may have exclusion criteria about cooperation, mental health issues, drug abuse, that sort of thing. So it’s important to make sure that all the patients studied in the trial are similar to answer the question in this defined population.
The participation in a clinical trial is something that is decided upon by both the patient and the investigator. So remember, the patients need to willing participate. This is a choice that the patients have. They have to decide if they want to go into a clinical trial. And even once the patient decides that they’re willing to go into the clinical trial, the investigator needs to make sure that they meet all the inclusion and exclusion criteria. So they both need to be on the same page.
It’s very important for a patient to know all the options they have for their care before participating in a clinical trial. It needs to be a totally voluntary decision. It shouldn’t change the care that you receive by your physician. So one thing that patients need to know is that this is ultimately their decision to participate. And then, of course, it’s important to know the details about the trial. The responsibilities, the risks of the trial related medication or any trial related procedures.
There are many reasons a clinical trial can be successful or unsuccessful. It can be unsuccessful if the medication truly doesn’t work and that’s one of the reasons we do clinical trials. We want to understand if a medication works in a particular patient population. So that’s an important reason that it might not be successful. Other reasons might be that it was designed poorly. A poor end point was chosen. There could be a number of different other issues.
Sometimes we don’t know the results of clinical trials for a long time. A patient might be enrolled at a site early in the trial and it may take another year or two or three to finish enrolling the clinical trial. So sometimes it seems like they don’t know the results but it may just be because the trial’s not over. Often times the investigator can share the results of the trial with the patients once all is said and done.
There are many clinical trials for patients with diseases and there are other options for patients who don’t have specific disease. Many clinical trials want to look at healthy controls to see the effect of a therapy in those patients as well. And then of course the Phase I trials often involve normal controls. Usually when a patient participates in a clinical trial it should not cost them any money and in fact all of the procedures that are specifically for the trial should be covered as part of the clinical trial.
Clinical trials are ways to learn about therapies. And sometimes we don’t know the effects of the therapy so there are potentially situations where there might be side effects of a therapy or side effects of a procedure that the patient might consider is not the safest option for them and that’s an important thing for the patient to consider before they go into a clinical trial. Remember by the time a patient is approached about a clinical trial, usually the FDA has signed off on for their study and of course the IRB has reviewed it and has assessed the risks of the study. Sometimes we take risks in order to get benefits as well. And this has to be balanced with patients, their diagnosis and how sick they are.
Clinical trials are so important because it’s our way to learn about therapies that we want to get out to patients. For example, in the disease that I take care of, it’s a rare disease, the very first therapy was approved the year I started practicing, 1995, that was the first time we had anything for patients. Now, I tell them about a dozen different options that they have to treat their disease. And they’re doing so much better than they were in 1995. And we wouldn’t have those therapies if it weren’t for all of the patients who participated in clinical trials before that.
While clinical trials are voluntary for any patient it is important for a patient to consider doing good for their community and their disease state and how their participation in the clinical trial might help further knowledge and lead to therapies for patients like them down the road.
I’m Vallerie McLaughlin and I’m aware that I’m rare.
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