The geographical distribution of leadership in globalized clinical trials.

BACKGROUND: Pharmaceutical trials are mainly initiated by sponsors and investigators in the United States, Western Europe and Japan. However, more and more patients are enrolled in Central and Eastern Europe, Latin America and Asia. The involvement of patients in new geographical settings raises questions about scientific and ethical integrity, especially when experience with those settings is lacking at the level of trial management. We therefore studied to what extent the geographical shift in patient enrolment is anticipated in the composition of trial management teams using the author nationalities on the primary outcome publication as an indicator of leadership. METHODS AND FINDINGS: We conducted a cohort-study among 1,445 registered trials in www.clinicaltrials.gov that could be matched with a primary outcome publication using clinical trial registry numbers listed in publications. The name of the sponsor and the enrolment countries were extracted from all registrations. The author-addresses of all authors were extracted from the publications. We searched the author-address of all publications to determine whether enrolment countries and sponsors listed on registrations also appeared on a matched publication. Of all sponsors, 80.1% were listed with an author-address on the publication. Of all enrolment countries, 50.3% appeared with an author-address on the publication. The listing of enrolment countries was especially low for industry-funded trials (39.9%) as compared to government (90.4%) and not-for-profit funding (93.7%). We found that listing of enrolment countries in industry-funded trials was higher for traditional research locations such as the United States (98.2%) and Japan (72.0%) as compared to nontraditional research locations such as Poland (27.3%) and Mexico (14.1%). CONCLUSIONS: Despite patient enrolment efforts, the involvement of researchers from nontraditional locations in trial management as measured by their contribution to manuscript writing is modest. This division of labor has significant implications for the scientific and ethical integrity of global clinical research