Promoting Informed Decision Making for Comparative Effectiveness Randomized Trials.

Abstract

The US Code of Federal Regulations governing human participants research requires that investigators disclose reasonably foreseeable risks of a research study to prospective participants during the informed consent process. Although this mandate appears straightforward, controversy surrounds how investigators should define and describe risks of comparative effectiveness randomized clinical trials (CE-RCTs) that compare treatments within accepted standards of care. The Office for Human Research Protections (OHRP) has published draft guidance prompted by the controversy of the Surfactant, Positive Pressure, and Pulse Oximetry (SUPPORT) trial of oxygenation targets in premature infants to address this question. The draft guidance concludes that “if a research study examining standards of care includes as a purpose evaluating identified risks associated with those standards of care, the identified risks associated with the standards of care being evaluated that are different from the risks of standards of care at least some of the subjects would be exposed to outside of the research study are generally considered…to be reasonably foreseeable risks of research.” 1 Given the often subtle ways in which participation in a CE-RCT alters risk compared with treatment outside the trial, accurately framing disclosures is challenging. Unfortunately, if implemented, the OHRP’s draft guidance will impede rather than promote informed decisions. Investigators and institutional review boards that follow the guidance are likely to formulate consent documents that mischaracterize the disadvantages of the study treatments compared with one another as foreseeable risks of participation, unnecessarily dissuading patients from enrolling. The OHRP should reconsider its guidance and instead support disclosures aimed at the following simple goal: to provide patients with information, including about risks, that they need to decide whether to join the trial, request one of the study treatments outside the trial, or select another available treatment. Organizing disclosure around 4 core questions can effectively accomplish this goal (Table).