Hollow Hunt for Harms

Harms of medical interventions are systematically underestimated in clinical research. Numerous factors—conceptual, methodological, and social—contribute to this underestimation. I articulate the depth of such underestimation by describing these factors at the various stages of clinical research. Before any evidence is gathered, the ways harms are operationalized in clinical research contributes to their underestimation. Medical interventions are first tested in phase 1 “first in human” trials, but evidence from these trials is rarely published, despite the fact that such trials provide the foundation for assessing the harm profile of medical interventions. If a medical intervention is deemed safe in a phase 1 trial, it is tested in larger phase 2 and 3 clinical trials. One way to think about the problem of underestimating harms is in terms of the statistical power of a clinical trial—the ability of a trial to detect a difference of a certain effect size between the experimental group and the control group. Power is normally thought to be pertinent to detecting benefits of medical interventions. It is important, though, to distinguish between the ability of a trial to detect benefits and the ability of a trial to detect harms. I refer to the former as power_B and the latter as power_H. I identify several factors that maximize power_B by sacrificing power_H in phase 3 clinical trials. If a medical intervention is approved for general use, it is evaluated by phase 4 post-market surveillance. Phase 4 surveillance of harms further contributes to underestimating the harm profile of medical interventions. At every stage of clinical research the hunt for harms is shrouded in secrecy, which further contributes to the underestimation of the harm profiles of medical interventions.