Families Online Magazine

Marvin Ackerman, MD - Is Research fair to the participants?

Okay, so maybe it’s unfair to drill holes in someone’s skull the way those brain surgeons were doing in my recent article, but hey, what’s wrong with testing a medication by comparing it to a fake as a control?

Anyway, the test subjects have about a 50/50 chance of getting the medication, and are probably getting paid pretty well, in one manner or another, for acting as guinea pigs. So, what’s the harm?

Well, there are always do-gooders out there who are ready to find fault with anything, aren’t there? Doesn’t it seem as if some folks just can’t let things be? It’s unethical to use placebos as controls they complain, according to Miller from the NIH, and Shore from Glaxo-SmithKline writing in the Archives of Internal Medicine. Their commentary called “Unnecessary Use of Placebo Controls: The Case of Asthma Clinical Trials” claims that many of these critics cite the World Medical Association’s Declaration of Helsinki to back up their contention that researchers should be using proven effective treatments as controls instead of placebos, which do nothing to help the participants. The declaration was revised in October 2000 so that a clarified provision governing the ethics of placebo control now reads:

The benefits, risks, burdens, and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic, and therapeutic method exists.

To tell the truth, as with any controversial question, there seem to be good arguments for both sides of the placebo ethics debate. Suppose we examine some of the pros and cons as presented in the Archives article. A standard contention in favor of using placebos states that studies, which use active treatment modalities instead of placebos as controls are often fraught with “serious methodological weaknesses.” Miller and Shore decided to take a middle-ground position on the ethics of placebo control while reviewing three recent clinical trials of asthma treatments.

Those questioning the use of placebo as control for these trials were of the opinion that there was no such need given the scientific questions under investigation. All three were judged as possessing a potential risk of harm or discomfort to a large number of participants who were exposed to “potentially ineffective or toxic treatments.” This would be okay if the knowledge to be derived compensated for the risk. However, those individuals receiving placebo obtained no such benefit as determined by the commentators. They would not have objected if these were initial trials of an investigational treatment leading to proof of efficacy.

A second objection is made to those studies that utilize placebo as control when good treatment modalities exist. This approach denies appropriate treatment to those receiving placebo even though it is available. Evidently, this would be contrary to the tenets of the Declaration of Helsinki.

On the other hand, placebo-control defenders complain that there are times when its use is appropriate. For example, why should there be any objection if a valuable clinical trial poses no threat to those receiving the placebo? Furthermore, utilizing active treatment as a control to see whether the test medication is equivalent, better, or less effective can have distinct drawbacks from a methodological standpoint. Just because there is no difference between the two drugs does not prove that the new one is effective. Comparing a new drug to an older one means that you are comparing it to a drug that has been tested by someone else under different circumstances. The trial lacks so-called “internal validity.” Thus, a medication might be considered to be effective based on comparison to another medication, but compared to placebo might be proven ineffective. From another standpoint, proponents of placebo-control claim that such trials are more efficient requiring smaller sample sizes.

The authors went through considerable effort in order to categorize the various types of studies utilizing several asthma clinical trials as examples. They concluded that the use of placebo-control might be better regulated by carefully considering the individual circumstances of any given trial. They contended that placebo-controls “should be used sparingly, mainly in initial trials to test the efficacy of investigational agents.” Finally, they continued, “investigators should be required to provide compelling justifications for the use of placebo controls,” and historical control databases based on “well-designed placebo-controlled” studies should be developed as aids in validating results of active-controlled trials.

What do you think? Are we becoming too picayune about looking out for the rights of these individuals? After all, don’t these patients sign wavers knowingly? They are fully aware that they may be getting a placebo, yet they participate anyway in the hope that something good may come out of their sacrifice. They may also participate because the stipend for doing so is rather enticing or the cost of treatment might otherwise be prohibitive. If you had a serious, debilitating, or potentially fatal disease would you take a chance and let someone drill holes in your skull even though you have a fifty-fifty possibility of actually getting the new treatment? The question may not even apply if the researchers plan to provide you with treatment eventually, on condition that the results were promising. Come to think of it, that sounds like a pretty good deal, doesn’t it?

Cartoons and Poems following each article are created and copyrighted by Dr. Ackerman and cannot be copied or reproduced without his permission.