Participant Recruitment From Low- and Middle-Income Countries for Pivotal Trials of Drugs Approved by the U.S. Food and Drug Administration : A Cross-Sectional Analysis.

Abstract

Many participants in clinical trials supporting U.S. Food and Drug Administration (FDA) drug approvals are recruited from outside the United States, including from low- and middle-income countries (LMICs). Where participants are recruited for pivotal trials has implications for ethical research conduct and generalizability. To describe LMIC recruitment for pivotal trials of newly approved drugs for cancer, neurologic disease, and cardiovascular disease. Cross-sectional analysis. Pivotal trials of new cancer, cardiovascular, and neurologic drugs approved from 2012 to 2019 matched to ClinicalTrials.gov, FDA records, and publications. Host countries and available per country enrollments were extracted. The primary end point was the proportion of pivotal trials enrolling participants in LMICs. The secondary end point was the proportion of pivotal trial participants contributed by LMICs for each indication area. Data were obtained from 66 new drugs and 144 pivotal clinical trials. All cardiovascular approvals (12 drugs, 29 trials) and neurologic approvals (26 drugs, 54 trials) were analyzed, as well as a random sample of cancer approvals (28 of 85 drugs [33%]) matched to their pivotal trials (61 of 210 trials [29%]). Among the trials, 56% in cancer, 79% in cardiovascular disease, and 56% in neurology recruited from an LMIC. For multicountry trials, country-level enrollment figures were not available for 71 trials (55%). For those reporting per country enrollment, the percentage of participants recruited from LMICs was 8% for cancer trials, 36% for cardiovascular trials, and 17% for neurology trials. The study was limited to FDA-approved drugs in 3 areas, including a sample of cancer drugs. Pivotal trials of nonapproved drugs or drugs for other indications were not captured. Most pivotal trials for FDA-approved drugs recruit from LMICs. Publications and FDA documents generally do not provide country-level data on recruitment. None.