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. 2021 May 3;4(5):e217075.
doi: 10.1001/jamanetworkopen.2021.7075.

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

Jennifer E Miller  1   2 , Michelle M Mello  3   4 , Joshua D Wallach  5 , Emily M Gudbranson  1 , Blake Bohlig  6 , Joseph S Ross  1 , Cary P Gross  1 , Peter B Bach  7
Affiliations

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

Jennifer E Miller et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Miller reported receiving grants from Arnold Ventures, Milken Institute Center for Faster Cures, and the National Institutes of Health (NOT-OD-20-121) during the conduct of the study and serving on the bioethics advisory committee for Alexion and the board of directors for Bioethics International. Dr Mello reported receiving grants from Arnold Ventures during the conduct of the study. Dr Wallach reported receiving grants from Arnold Ventures, Yale-Mayo Clinical Center for Excellence in Regulatory Science and Innovation, and the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (award K01AA028258) outside the submitted work. Dr Ross reported receiving grants from the Food and Drug Administration, Johnson & Johnson, Medical Devices Innovation Consortium, Agency for Healthcare Research and Quality, National Institutes of Health and the National Heart, Lung, and Blood Institute, and the Laura and John Arnold Foundation outside the submitted work. Dr Gross reported receiving grants from Johnson & Johnson and the National Comprehensive Cancer Network (through Pfizer and AstraZeneca), personal fees from Genentech during the conduct of the study, and travel reimbursement and speaking fees from Flatiron, Inc outside the submitted work. Dr Bach reported receiving grants from Kaiser Permanente and Arnold Ventures; personal fees from Mercer, United Rheumatology, Foundation Medicine, Morgan Stanley, New York State Rheumatology Society, Oppenheimer & Co, Cello Health, Anthem, Magellan Health, Kaiser Permanente Institute for Health Policy, Congressional Budget Office, America’s Health Insurance Plans, Geisinger, Meyer Cancer Center of Weill Cornell Medicine, and the National Pharmaceutical Council; travel reimbursement and stock from Oncology Analytics; personal fees and stock from EQRx; and consulting fees and stock from Grail outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Percentage of Drugs Approved for Sale in All the Countries Where They Were Tested to Gain US Food and Drug Administration (FDA) Approval, by Income Level
Figure 2.
Figure 2.. Percentage of Countries Hosting Trials for US Food and Drug Administration (FDA) Drug Approvals That Received Marketing Approval for Those Drugs Within 5 Years, by Income Level
Figure 3.
Figure 3.. Percentage of Drugs Approved for Sale in the Countries Where They Were Tested for US Food and Drug Administration (FDA) Approval, by Geographical Regions
See this image and copyright information in PMC

References

    1. Galkina Cleary E, Beierlein JM, Khanuja NS, McNamee LM, Ledley FD. Contribution of NIH funding to new drug approvals 2010-2016. Proc Natl Acad Sci U S A. 2018;115(10):2329-2334. doi: 10.1073/pnas.1715368115 - DOI - PMC - PubMed
    1. Kantarjian H, Rajkumar SV. Why are cancer drugs so expensive in the United States, and what are the solutions? Mayo Clin Proc. 2015;90(4):500-504. doi: 10.1016/j.mayocp.2015.01.014 - DOI - PubMed
    1. Langreth R, Migliozzi B, Gokhale K. The U.S. pays a lot more for top drugs than other countries. Bloomberg. Published December 18, 2015. Accessed November 20, 2020. https://www.bloomberg.com/graphics/2015-drug-prices
    1. Pitts P. How other countries freeload on U.S. drug research. Wall Street Journal. Published February 21, 2017. Accessed November 20, 2020. https://www.wsj.com/articles/how-other-countries-freeload-on-u-s-drug-re...
    1. Kanavos P, Ferrario A, Vandoros S, Anderson GF. Higher US branded drug prices and spending compared to other countries may stem partly from quick uptake of new drugs. Health Aff (Millwood). 2013;32(4):753-761. doi: 10.1377/hlthaff.2012.0920 - DOI - PubMed

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