24 Feb 2011


“Doctor, am I on active drug or placebo?” asked my patient one day. She was enrolled in a randomized controlled trial in liver disease.

“No, we deliberately make sure that neither you nor I know the treatment assignment so that we can assess the treatment effect fairly. Otherwise, I may treat you differently just because I know what treatment you are on,” I tried to explain.

“But if I am on placebo right now, are you delaying my treatment?”

Was I delaying treatment?

In this case, I was quite comfortable in explaining that although the mechanism of action of the new drug looked promising, there really was not any clinical data to show that it worked. That was precisely why the pilot study had to be performed. If she was not in that trial, the unproven drug would not be offered anyway. Meanwhile, she was receiving all other optimal treatments. This is the principle of equipoise. Some people hold the belief that clinical trials are only ethical when there is no existing evidence that one of the study arms is worse than others.

However, equipoise often does not happen in clinical trials. In medical jargons, we move forward to large phase 3 trials because the results of early phase 2 trials look good. If equipoise is essential, most clinical trials should be abandoned and drugs would be registered with preliminary data. This is obviously problematic. If new drugs are not fully evaluated, the efficacy may be inaccurately determined and important side effects may be missed.

In this month’s New England Journal of Medicine (2011;364:476-80), Franklin Miller and Steven Joffe argued that the concept of equipoise was flawed. Especially because new drugs are often very expensive nowadays, it is important to confirm it works before its introduction to the market.

I would not bore readers with the arguments. Suffice it to say, we are not doing favor to our patients by enrolling them to clinical trials. The aim, however, is to develop better treatments to benefit future patients. Participants in clinical trials may potentially be receiving less effective treatment or treatment with more side effects. This should be explained clearly to our patients, and we should be grateful.

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