081: Country Contribution of Investigators to Pivotal Clinical Trials & their Primary Publications of New Drugs Approved by the US Food & Drug Administration

Statement of Purpose: A pivotal clinical trial (PCT) is a primary source of evidence for supporting regulatory approval decisions for a new drug. Many PCTs are conducted in >1 country to ensure timely patient enrollment and to facilitate approval in multiple countries. This study aimed to analyze the contribution of investigators by country to PCTs of new drugs approved by the US Food & Drug Administration. We also investigated the authorship of the publications for those PCTs.

Description of Methods & Materials: Information on PCTs of new drugs approved by the FDA in 2012-2021 was collected from the label of each drug. The primary publications, defined as papers reporting the main results used for regulatory approval, were identified from PubMed using the information provided in the 'CLINICAL STUDIES' section of the full prescribing information of a label. For the identified primary publications, the lists of investigational sites and authors of the primary publications were extracted from clinicaltrials.gov and PubMed, respectively, and their country distribution was analyzed.

Data & Results: We identified 860 PCTs and 705 primary publications for 429 new drugs approved in 2012-2021. Out of 824 PCTs registered on clinicaltrials.gov, information on 62,613 investigational sites was available for 669 (81.2%) clinical trials. On the other hand, 7,471 authors (excluding company-affiliated authors) were identified from the primary publications. The majority of PCT sites were in the US (41.8%), followed by Germany, Canada, France, Spain, UK, Russia, Japan, Poland and Italy accounting for 28.5%. Likewise, the majority of authors of primary publications were affiliated with the US (47.1%), with the next nine top countries being Germany, UK, France, Canada, Italy, Spain, Japan, Australia and South Korea, accounting for 32.8%. North America (US and Canada) and Western Europe (Germany, France, Spain, UK and Italy) accounted for a substantial proportion of the PCT sites, with 45.3% and 17.0%, respectively, and an even higher proportion of the authors for primary publications, with 51.1% and 22.7%, respectively. The top 10 ranks on each list remained largely unchanged for 10 years. South Korea and Australia emerged as strong contributors in both investigational sites and authorships for oncology drugs while North America and Western Europe remained dominant.

Interpretation, Conclusion or Significance: The concentration of evidence generation for regulatory approval of new drugs has been predominantly centered in North America and Western Europe, with the US being the primary contributor. The dominance has become even greater for authorship contribution to primary publications of new drugs. This suggests a potential limitation in the generalizability of clinical trial data to other regions of the world. Given the growing importance of ensuring equality in clinical trial participation, efforts to increase participation from underrepresented regions are needed to ensure more representative and inclusive clinical trial data.

Disclosures: