Are people who participate in clinical trials patients or subjects? This may seem like a minor rhetorical difference, but I believe it has tremendous implications for health and biomedical research policy. Let me explain why –

Clinical trials are experiments to discover new knowledge. Their intent is to see if a new way of treating a specific disease or condition is better than, the same as, or worse than, another option – either a placebo or an established treatment. Therefore, when people agree to participate in a clinical trial they are participating in this experiment, and their fundamental goal for participating should be to help future patients by expanding biomedical and/or clinical knowledge. As part of their participation, they may receive some benefit – IF the experimental therapy does prove to be beneficial. Therefore, they are not patients; they are subjects within the clinical trial.

I often see phrases like “clinical trial patients” or “patients in clinical trials,” and I understand what they are talking about, since for many patients with serious conditions that lack good treatment options, clinical trials offer some hope. However, I think that the term muddles the distinction, and can lead to conflicting responsibilities for the clinician-investigators conducting the trials and the patient’s primary physicians. This is one reason that I believe that patients who elect to participate in clinical trials should maintain a relationship with their primary care physician during the clinical trial – even if the researcher in charge of the clinical trial is responsible for all their clinical care. This also means that the clinical investigator and the primary care physicians for the subjects in the clinical trial need to have regular communications – both before and during the person’s participation in the clinical trial.

When the person’s primary care physician is also the clinical investigator in the clinical trial, these lines are easily blurred, and this can lead to problems – something that all clinician-investigators struggle with. This is why clinical trials have protocols that are pre-approved by at least one Institutional Review Board (IRB) that is charged with protecting the rights and welfare of subjects in the clinical trial. (IRBs are also involved with monitoring the clinical trials and modifying the protocols as needed during the course of the trial.)

I was reminded about this issue by an article in the May 1^st issue of American Family Physician that discusses when and how it is OK to use a placebo in clinical practice, i.e. for patients rather than clinical trial subjects. The article lays out a bright line for physicians – “do not lie” – as well as referencing an older article* that lists five conditions that should be met before giving a placebo to a patient:

1. There is a well-established, durable physician-patient relationship
2. There is a concrete diagnosis that does not mandate or support the use of other “active” interventions
3. The patient specifically requests that the physician provide some form of intervention
4. The use of such agents is a consideration of last resort
5. The use of such agents does not substitute for, or interfere with, diagnostic and therapeutic diligence

The distinction here is between using a placebo clinically, and using it in a clinical trial. For someone to become a subject in a clinical trial, they need to first give their informed consent so they are aware of the risks involved with their participation. Having a physician give such informed consent in clinical practice when using a placebo might actually undermine the placebo effect, and thus remove any benefit the patient might receive from the placebo. The AFP article specifically counsels that if a patient asks about a recommended treatment that is a placebo, that an appropriate response from their physicians should be something like – this may not directly affect your condition, “but it may turn on other mechanisms that might be important for your health and make you feel better.”

Any additional thoughts on this issue?

* Bok, S., “The ethics of giving placebos,” Sci. Am. 1974; 231 (5): 17-23