I — The Issues
With few exceptions, every prescription and over-the-counter (OTC) drug and medical device marketed in the U.S. has to be approved by the Food and Drug Administration (FDA) for efficacy and safety. That is where clinical trials come into play. They provide the information required for clearance. It is critically important to realize that for any drug or device in a clinical trial it is impossible to know beforehand what the outcomes of the intervention — both favorable and unfavorable — will be. No one — not even the best informed minds — know that. That is the reason for having a clinical trial. The trial is based on an hypothesis — a.k.a,, a guess. Sometimes it is correct, sometimes not. If the outcomes, or the range within which they fall were understood, there would be no reason for the trial.
Not all clinical trials are successful. Some drugs do not even make it through Phase I (which determines if the drug is safe and the dosage levels). Others are withdrawn before they complete Phase II (which tests for efficacy and safety). They can be withdrawn because they are ineffective, unsafe or have damaging side effects or considered to be non-profitable. Still others may not offer a significant improvement over current therapy represented by the control group. Only some of the ones that get through those hurdles are ultimately cleared for marketing by the FDA.
The data are hard to come by. They would provide useful information in deciding whether to enter a clinical trial. Our numerous attempts to get them from the FDA were unsuccessful. What we do know is that in 2011 about 80% of the drugs that made it through the earlier stages and sought final approval, received it. It was somewhat higher for priority applications — those involving a significant improvement over a currently marketed product — and a little lower for standard applications. A significant number fall by the wayside before that.
The nature of a trial
In every randomized clinical trial (RCT) half the participants get the drug that is being tested, the other half get a “placebo”. That is, they just get a sugar pill — no treatment. They are called the control group. That approach makes it possible to compare the outcomes of both groups and determine statistically, whether the drug is safe and effective when compared to no treatment. Sometimes the new drug is compared to the current “standard of care”. From your perspective, when agreeing to participate in the clinical trial, it is important to understand that you cannot know whether or not you will, in fact, be getting the drug. Furthermore, if it is a “double-blind” study, the doctor doesn’t know either.
If you’re doing it with the hope or expectation that it will save your life, it will never do that. No intervention ever can. At most, it can extend your life or make you feel better in the time you have left — that is, improve the quality of your life. The fact of the matter is, however, that instead of improving it, the intervention can shorten your life or make you feel worse off, certainly in the short-run and perhaps long-term as well. For example, you may have to discontinue you current medications or not be able to vary the dosage.
As anyone who has been diagnosed with a critical illness can tell you, being in that situation causes considerable anxiety, depression and confusion, and makes it even more difficult to make the best decisions. Sometimes just the idea that you are ‘doing something’ can be a great relief, even if that ‘something’ may cause additional anxiety or debility in the future.
The best thing you can do is to have a patient advocate and a support team made up of members from your community, family, friends and practitioners to help you make the decision that is best for you. Dealing with anxiety and the fear of death or pain is paramount. Using stress-reduction techniques, meditation, counseling and prayer can be important tools when making important decisions. Poor decision-making often happens when we feel anxious, stressed or trapped. If you are feeling outside pressure from doctors, family members, etc. to enter a clinical trial or engage in treatments that you are uncomfortable with — it is important to step back, consider your options, discuss your concerns with a neutral party and then, and only then, make your decision.
Since there is no guarantee that it will improve your condition, what other potential benefits can there be from entering a clinical trial? Participation can provide improved care at no extra charge and closer monitoring of your condition. You may not be charged for medications. Furthermore, some clinical trials pay you for participating. If the study was done correctly you may be contributing to future knowledge. That is your legacy. It has little or nothing to do with your current or future well-being.
Realistically, any expectation that entering a clinical trial will improve your condition over and above what it was previously, is at best, uncertain. Some trials are just designed to determine the safety of a drug or the appropriate dosage. Only those that attempt to determine the efficacy of the treatment have any reasonable prospect of improving your condition. Just ask what kind of trial yours is; they are obligated to tell you.
Moreover, even if it helps, it opens up the question of whether the improvement is worth the real and financial costs involved. Those costs may include the additional debility, pain, suffering and anxiety resulting from the intervention and during the recovery period, the time and energy lost because of participation in the trial, and any extra expenses involved.
Sure, participation in the trial might help things, but who knows? The answer to that question is, “no one”. If you are willing to give it a try, just to find out, that’s up to you. Perhaps it would be a good idea to do it with your eyes open, recognizing what is involved and what you will be giving up when you do.
A closer look
Let’s take a closer look at what the intervention is likely to involve. Like any treatment — depending upon what is being tested — it involves taking a pill, having an injection, infusion, radiation or a surgical procedure, at least once or perhaps a number of times. Given the nature of any intervention there are a number of other important things to consider: Recovery takes time. It is time taken away from doing whatever else you would ordinarily do. The same thing goes for the time, effort and expense of getting to where the treatment takes place, the treatment time and any delays waiting for it and getting back home. As a consequence of the treatment and recovery from it, you may require additional support. Someone must provide it. That could require additional funds. Even if it doesn’t, those providing the support are giving up their time and effort. Economists include that as part of the cost of the intervention.
It is useful to understand that you will be faced with these issues. Taking them into consideration when making the decision will make it more likely that you will have a better outcome. Even if the ultimate outcome turns out to be favorable, what you can be sure of is that these issues will be part of the costs involved.
In spite of the chances against it, there are times when the test drug leads to a breakthrough, one that provides significant benefits. In fact, at times a trial is so successful that it is terminated and the medication is given to all patients, including those who were in the control group. [See AIDS Clinical Trial Group for examples.]
There are other times when the trial is discontinued because of unfavorable results. For example, the NIH stopped the trial of estrogen plus progestin because it increased the risk of breast cancer and lacked any benefit.
In our next post we will discuss how the stakeholders benefit from your participation in the clinical trial.