Speaker Willard Applefeld, MD, Duke University, discussed how IRBs should evaluate proposals that claim to compare “Standards of Care” in Comparative Effectiveness Research (CER), what evidence needs to be submitted to support a practice as genuinely “usual care practice”, and what reasonably foreseeable risks should be disclosed to subjects in research comparing “standards of care.” This presentation was delivered at the OHRP Research Community Forum co-sponsored with Northwell Health in May 2022.