Reader Response: AAN Position Statement: Ethical Issues in Clinical Research in Neurology

In their update to the AAN's statement on research ethics, Tolchin et al.¹ provided a thoughtful consideration of how to do clinical research but say little about when or why to conduct a randomized clinical trial (RCT). The 7-step criteria put forward by Emanuel et al.²—and on which the statement is based—speaks to this issue indirectly, but we suggest going even further. The AAN statement provides a valuable opportunity to mandate that the ethical justification for neurologic RCTs be explicit and codified. Specifically, we have proposed that RCTs be conducted only if there is uncertainty surrounding a clear hypothesis as explicitly demonstrated through a systematic review.³ Moreover, we have shown this standard is rarely met.⁴ We believe this issue is of pressing importance, especially in the era of COVID-19. For example, medicine has been challenged by unfounded claims about the efficacy of hydroxychloroquine for COVID-19,⁵ which has provoked calls for RCTs. Researchers have responded: a search of clinicialtrials.gov reveals 133 active or upcoming trials. Are all these trials necessary? Are any? Hydroxychloroquine has significant risks. Without transparent and codified standards for determining when RCTs should be performed, patients will suffer from being recruited into useless, redundant, or harmful trials.