Evaluation of Drug Trials in High-, Middle-, and Low-Income Countries and Local Commercial Availability of Newly Approved Drugs.

Importance: Clinical research supporting US Food and Drug Administration (FDA) drug approvals is largely conducted outside the US.

Objective: To characterize where drugs were tested for FDA approval and to determine how commonly and quickly these drugs received marketing approval in the countries where they were tested, both overall and by country income level and geographical region.

Design, Setting, And Participants: This cross-sectional analysis of trials supporting FDA approval of novel drugs in 2012 and 2014, sponsored by large drug companies, did not involve human participants. The settings were the countries hosting trials supporting US drug approval. Data sources included Drugs@FDA, ClinicalTrials.gov, PubMed, Google Scholar, EMBASE, and drug regulatory agency websites. Data analysis was completed March through September 2020.

Main Outcomes And Measures: The primary outcomes were the proportion of drugs approved for marketing in the countries where they were tested for FDA approval within 1, 2, 3, 4, and 5 years of FDA approval and the proportion of countries contributing participants to trials supporting FDA approvals receiving market access to the drugs they helped test within 1, 2, 3, 4, and 5 years of FDA approval.

Results: In 2012 and 2014, the FDA approved 34 novel drugs sponsored by large companies, on the basis of a total of 898 trials, 563 of which had location information available. Each drug was tested in a median (interquartile range [IQR]) of 25 (18-37) unique countries, including a median (IQR) of 20 (13-25) high-income countries, 6 (4-11) upper-middle-income countries, and 1 (0-2) low-middle-income country. One drug was approved for marketing in all testing countries within 1 year of FDA approval and 15% (5 of 34 drugs) were approved in all testing countries within 5 years of FDA approval. Of the 70 countries contributing research participants for FDA drug approvals, 7% (5 countries) received market access to drugs they helped test within 1 year of FDA approval and 31% (22 countries) did so within 5 years. Access within 1 year occurred in 13% (5 of 39) of high-income countries, 0 of 22 upper-middle-income countries (0%), and 0 of 9 lower-middle-income countries (0%), whereas at 5 years access rates were 46% (18 of 39 countries), 9% (2 of 22 countries), and 22% (2 of 9 countries), respectively. Approvals were faster in high-income countries (median [IQR], 8 [0-11] months) than in upper-middle-income countries (median [IQR], 11 [5-29] months) or lower-middle-income countries (median [IQR], 17 [11-27] months) after FDA approval. Access was lowest in African countries.

Conclusions And Relevance: These findings suggest that substantial gaps exist between where FDA-approved drugs are tested and where they ultimately become available to patients, raising concerns about the equitable distribution of research benefits at the population level.