Dr. Williams: Welcome to another episode of our new podcast series, “Q&A with FDA”, from the FDA’s Division of Drug Information. In this podcast series, we answer some of the most frequently asked questions that we’ve received from the public.
My name is Dr. Celia Williams. In today’s episode, we’ll be discussing the basics of clinical trials. This is a particular topic of interest, as we receive hundreds of questions on clinical trials every month. In fact, we have responded to over 1,100 inquiries on this topic in the past 6 months alone. To shed some light on clinical trials, I am joined by Dr. Bob Temple, a key leader in American medicine who currently serves as Senior Advisor for Clinical Science in FDA’s Center for Drug Evaluation and Research. Dr. Temple has a long-standing interest in the design and conduct of clinical trials. He has written extensively on this subject, especially on choice of control group in clinical trials, evaluation and interpretation of active control trials, trials to evaluate dose-response, and trials using “enrichment” designs to help improve efficiency. Hi Dr. Temple, thank you for joining us today!
Dr. Temple: It's my pleasure. Thank you for inviting me.
Dr. Williams: Rumor is that you are celebrating your 50th year with FDA. Clearly you have had a profound impact on the regulation and development of human therapeutics.
Dr. Temple: Actually, it's my 51st year, and when I first joined FDA, I had no expectation, particularly I didn't know much about it. But I have to say, it's been life changing for me. The nature of the people who are here and their interest and their interest in getting it right, and their intelligence has just been thrilling. And of course, the problems that FDA's here to deal with and help resolve are very important. It's very critical that drugs work and that they not hurt you. And if you don't have the right kinds of study designs to help you assess those things, you won't get it right. So it's extremely important and the whole world depends on us and the other places that are doing the same thing to get the answers right. It's important that medicines do what they're expected to do, or they're hoped to do, and that they not do things that are adverse.
Dr. Williams: Well, we are honored and grateful to have you here and would love for you to share your extensive expertise on clinical trials with us.
Dr. Temple: Well, there's, you know, there's an almost unlimited amount of things one can talk about. Basically, it's worth remembering that clinical trials are research studies. You're intending to learn something from the trial that you're using treatments in and people have to volunteer to be in the trial. You can't have the trial without getting their consent. And it's very important to understand that part of it. When carefully designed and conducted, they are the safest, fastest and most reliable method to find new effective treatments and ways to improve health. In the clinical trial, there's usually a comparison between the treatment and a similar group of patients who don't get any treatment. And you look for what the difference is and you attribute that to the new treatment.
Clinical trials can do a lot of things. They can determine whether new drug or new device is safe and whether it does what you wanted it to do. But clinical trials can also compare two treatments, see whether one treatment is better than another in ways that you didn't necessarily anticipate. You also get to look at what the right dose is. You know, people have an idea from the animal studies and so on and from there, going in biases is what the right dose is going to be, but you don't really know until you test it. So those response trials are a very important aspect of getting the drug right.
And of course, it's also important to study a wide range of populations. Drugs don't behave the same in everybody. One of the differences is the difference in age. That's important. As people age, their ability to metabolize drug or excrete the drug can change, and that can alter the effectiveness and the safety of it. So you need to study all these things. And as many of them as you can possibly do.
Dr. Williams: What are reasons that people may want to participate in clinical trials?
Dr. Temple: Well, the most obvious reason in some sense is that because what's being studied is the treatment for a disease they have that doesn't have any good treatment, or a disease they have where standard treatments have been tried and didn't do very well. That's a very obvious reason for being in a trial. But some people do it in, at least in part, because they recognize that it's valuable to people, and to the population, to have drugs properly studied and they may want to be helpful. They want to contribute to the advancement of medical knowledge and that's their reason. So there's a lot of good reasons. I think the more important one is that they have the disease and they're not completely happy with available therapy.
Dr. Williams: And how is it determined whether a person could participate in a particular trial?
Dr. Temple: Well, of course, as you as your question suggests, not everybody who wants to get into a trial will be accepted. Trials have fairly strict criteria called eligibility criteria that say who can participate. You have to have the disease in the right degree of severity, depending on what the trial is.
You also may be particularly interested in people who have failed on prior therapies. That's an area of particular interest because you want to see if your new drug, which has a different mechanism of action, say, works in people who haven't responded to the previous therapy.
And then you're also frequently interested in the presence of other conditions, bad kidney function, bad liver function. Does that make a difference in the way a drug responds? So we're interested in all of those things because they're all potentially important.
Dr. Williams: Dr. Temple, you mentioned that when carefully conducted, clinical trials are the safest and fastest way to find new treatments and ways to improve health. What does FDA do to ensure the safety of clinical trials?
Dr. Temple: Well, we look at them and make sure that the right tests are being done to see about whether there's any particular risks, and that the trial is being monitored properly. You have to watch them along the way and do appropriate tests to see no harm is coming to them.
The other thing that's worth mentioning is you also want a group of researchers who are skilled in these things. They need to understand about the nature of the trial because without that you can't give proper informed consent to people. And you need to sort of understand what the potential risks are as well as you can, and by reading up on the situation, understanding the underlying disease and things like that. There's a lot of work for people running a trial to do.
Dr. Williams: In addition to FDA, are there other groups that oversee clinical trial safety?
Dr. Temple: Well, there are, when any trial’s being done in an institution, there's generally an Institutional Review Board in that place, in that university or whatever it is, that is reviewing and monitoring the research, and they're experienced in trials, they understand the ethics and they understand all those things. So they actively participate and there may also be special groups with particular interests in particular diseases who participate actively and try to help the trials be as good as possible at what they're supposed to do.
Dr. Williams: In many clinical trials, the experimental drug is compared to a placebo - sometimes called a sugar pill. Why do trials include a placebo?
Dr. Temple: Well, it's worth remembering the whole point of the trial is to see what the drug does, what are the good things it does, but also what are the bad things it does. If you just sort of treat everybody without a control group, without another group of people that you're looking at to compare to the treated group, then the things that happen in the ordinary course of life, and there are things that happen. I mean, people with various conditions and diseases are probably a little older, and they're going to have other things happen to them. Some things happen just with age. So what you have to know, is, what you need to know what the drug does is to compare with the similar group of people watched in the same way and being treated in every other way that is similar to the drug treatment group. That is, they need to be the same except for getting the drug. And then if you see differences between the placebo group and the treated group, you can attribute them to the drug. You, among other things, you don't want the investigator to know who's getting which drug because they may have an interpreted bias when they do. If something happens, they may be more inclined to believe that it's due to the drug if it happens in the drug group, if they know who's getting the drugs. So you don't want them to know that because you want them to be completely neutral on these matters, so that you can tell what is really happening as a result of the direct treatment.
Dr. Williams: Are there restrictions on who can conduct clinical trials and where they can be conducted? Does FDA conduct the trials?
Dr. Temple: Let me do the last question first. FDA for the most part does not conduct the clinical trials. I wouldn't say we never have, but it's not the usual. Certainly, when a drug is being developed, we do not do the trials. Clinical trials are done by organizations like pharmaceutical companies, but also by federal agencies, by the NIH - they definitely do trials, National Institutes of Health, that is. And then there can be a wide variety of people who have areas of interest who will offer themselves as willing to carry out the trials and their experience may enormously help. What we do is we look over the design of the trials and make sure they are credible designs with the capability of distinguishing what the drug effect is. We also make sure appropriate safety analyses are carried out. We do oversee the conduct of trials. We go on-site and we may see that they're doing the right things. We certainly read the protocols to see that they are adequately protecting the rights of people and are assuring the quality of the trial. So we care about the design and conduct of the trials, but we don't do them.
Dr. Williams: Do you have advice for people thinking about joining a clinical trial?
Dr. Temple: We think, you know, that the greatest source of information about drugs and their effectiveness comes from trials and that this information is enormously valuable not only to the people in the trials, of course, but also to the whole community. So if you have a condition that is being studied, you can help the world deal with that condition by participating in a clinical trial. And you should also know that trials are very careful about protecting participants, telling them what's going on, giving them the results of the trials. That's a, a point of interest. People didn't always get the results of the trials they were in, but now nowadays they actually do. And, the people who do the trials are very interested in the health of the participants and they worry about these things and they watch closely.
So, the person entering a trial and thinking about it, should understand what's going to happen in the trial. They should understand, apart from the test drug, what other things they will be treated with, what kind of conditions. They obviously need to have to know whether any costs will come with the trial. In general, most of the costs of a trial are borne by the person doing the test. And they should ask as tough questions as possible, about the likely benefits and the risks associated with participating.
It's very important for people to understand how much advances in medicine depend on active participation of people in trials.
Dr. Williams: Thank you Dr. Temple for speaking with us today!
There are many resources for individuals and healthcare professionals to search and learn more about clinical trials. ClinicalTrials.gov is a great database to conduct searches for clinical trials. FDA also has a clinical trial search feature and information about clinical trials on its “Clinical Trials: What Patients Need to Know” webpage.
Thanks for tuning in to “Q&A with FDA” podcast series. The full podcast and transcript of this recording is available at fda.gov/QAwithFDA. And if you have drug-related questions, reach out to us at email@example.com.