Systematic review of approaches to informed consent in recent high-impact clinical trials

The U.S. Food and Drug Administration (FDA) recently harmonized its regulatory criteria for waivers and alterations of informed consent with the U.S. Common Rule. We conducted a systematic review of clinical trials in the two highest-impact clinical journals in the U.S. to better understand practice-changing trials that are being conducted in the U.S. without prospective written informed consent. One in ten trials in our sample were conducted without prospective written informed consent. Such trials accounted for 93.1% of patient-subjects in our sample, enrolling nearly 3 million individuals. Further guidance would support socially valuable research while ensuring appropriate oversight.