***Analyze the Placebo Case (below) as though you are the primary reviewer who must present your questions, reasoning, and proposed conclusions to your fellow IRB members for their discussion and decision***
Placebo Case
A psychiatrist wants to study a new investigational medication for Attention Deficit Hyperactivity Disorder (ADHD). Adults with ADHD will be withdrawn from their current medications, if any, and then randomized to receive either placebo or the investigational agent for six weeks. The primary outcome measure is a standardized self-assessment scale, which each subject will be asked to complete twice a day and then return by phone, fax or e-mail to the research center.
Questions to be answered 1 - 8:
1. Is use of a placebo justified for these subjects? Some are on medication and some are not. What is the right subject population – subjects who are being effectively treated with current medications? Subjects who have never taken medication? Subjects for whom medication has not worked well? How should the subjects be chosen, and why?
2. If you knew that a pharmaceutical firm sponsored this study, would that make you less or more likely to think that a placebo comparison is appropriate?
3. What is the value of the data from comparison with a placebo? Why make this comparison and not a comparison with approved medications, or with behavioral interventions?
4. Are the outcome measures adequate to produce valuable data?
5. Are there other issues regarding the design and/or ethics of this trial that should be considered? Are any protections or safeguards needed for the subjects? Is the six-week duration long enough? Too long or too short?
6. What should the consent form say about the study?
7. Imagine that you are an internist or family physician in a multispecialty practice, and the psychiatrist is your colleague. If you are asked to refer appropriate patients to your colleague to be recruited into the study, should you do so? What if the psychiatrist asks you to give appropriate patients information about the study and review the consent form with them?
8. Imagine that one of your patients says to you: “I think I might have ADHD; my 10-year-old son was recently diagnosed. I saw a flier in the waiting room about a study that the psychiatrist in this practice is doing, and I’d like to join it, so that I can get free treatment.” How should you respond?
Regulatory and Ethical Background:
When an IRB reviews study protocols like this, its role is to decide whether the proposed trial has validity and value, and consider how it can be made the best it can be. The IRB can decide not to approve a study because they conclude it can’t be improved enough to be a good study, but generally should not refuse to approve a study because they decide that the investigators ought to do a different, “better” study instead. However, it can be very challenging to decide when questions about a placebo design mean a study is just not good enough to do, because placebos are controversial. Thus, exploring comparisons with different study designs, identifying the goals that can be met with a given design, and trying to understand the reasoning behind placebo-controlled trials like this can be helpful when IRBs are doing their work – and that broad perspective is what we want to take on in our MAPS discussion, whether our groups take on the roles of IRB members, researchers, clinicians, or patient advocates.
Just in case it is useful, the regulatory definition of minimal risk is: “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”