Country Contribution to Investigators of Pivotal Clinical Trials and Their Primary Publications of New Drugs Approved by the <scp>US</scp> Food and Drug Administration, 2012–2021

Pivotal clinical trials (PCTs) are often conducted across multiple nations and regions to achieve geographic, racial, or ethnic diversity. However, the diversity of PCT participants remains inadequate. PCTs for new drugs approved by the US Food and Drug Administration in 2012-2021 and their primary publications (PPub) were identified from the label and review documents. The country information about the PCT investigators and PPub authors were extracted from the PPubs or clinicaltrials.gov. The racial/ethnic diversity of PCT participants as reported in PPubs was assessed using the Diversity Index (DI). For 429 new drugs, 734 PCTs and 718 PPubs were identified. North America and Western Europe (NAWE) contributed the largest proportion of PCT investigators, PPub authors, and lead authors (62.9%, 81.7%, and 90.9%, respectively). Of 521 PPubs that reported the racial/ethnic distribution of PCT participants, the median DI was low at 0.33 (interquartile range 0.18-0.46) and only 16.3% PPubs had a DI >0.5. The number of PPub authors in non-NAWE and the number of countries of PPub authors in non-NAWE was significantly associated with the racial/ethnic diversity of PCT participants (OR 1.17 [95% CI 1.08-1.26] and OR 1.25 [1.08-1.46], respectively). Evidence generation for the regulatory approval of new drugs has been predominantly centered in NAWE. The dominance is even more pronounced in the authorship of PPubs. To improve the racial/ethnic diversity of PCT participants, investigators from non-NAWE countries should be encouraged to play more leadership roles, thereby increasing their likelihood of serving as authors in PPub.