Author Response: AAN Position Statement: Ethical Issues in Clinical Research in Neurology.

Abstract

We thank Drs. Dewar and Shamy for their comment on our article1 and applaud their attention to the ethical and scientific question of when a randomized controlled trial (RCT) is justified. The 7 principles endorsed in our position statement—social value, scientific validity, fair participant selection, favorable risk-benefit ratio, independent review, informed consent, and respect for participants—provide a framework for deciding when an RCT is ethically justified.1 We agree that systematic reviews can help to evaluate the social value and scientific validity of a proposed RCT. However, we disagree with a requirement that a systematic review is a necessary prerequisite to an RCT. Observational studies and randomized trials have different and complementary advantages and roles in the clinical research enterprise. Well-conducted randomized trials have advantages over observational studies in internal validity and the ability to balance known and unknown confounders between study arms.2 Consequently, randomized trials have at times overturned the results of previous observational studies.3,4 Similarly, our inability to replicate the findings of many high-impact studies—the “replication crisis”—raises the need for more replication of existing studies.5 Therefore, we respectfully disagree with a universal mandate that randomized trials be conducted only where systematic reviews have been performed and demonstrated uncertainty surrounding the hypothesis.