Assessment of FDA-Approved Drugs Not Recommended for Use or Reimbursement in Other Countries, 2017-2020

Abstract

ImportanceDrug expenditures in the US are higher than in any other country and are projected to continue increasing, so US health systems may benefit from evaluating international regulatory and reimbursement decision-making of new drugs.ObjectiveTo evaluate regulatory decisions and health technology assessments (HTAs) in Australia, Canada, and the UK regarding new drugs approved by the US Food and Drug Administration (FDA) in 2017 through 2020, as well as to estimate the US cost per patient per year for drugs receiving negative recommendations.Design and SettingIn this cross-sectional study, recommendations issued by agencies in Australia, Canada, and the UK were collected for new drugs approved by the FDA in 2017 through 2020. All data were current as of May 31, 2022.ExposuresAuthorizations and HTAs in selected countries.Main Outcomes and MeasuresAll FDA-approved drugs were matched by active ingredient to decision summary reports published by drug regulators and HTA agencies in Australia, Canada, and the UK. Regulatory approval concordance and reasons for negative recommendations were assessed using descriptive statistics. For drugs not recommended by an international agency, the annual US drug cost per patient was estimated from FDA labeling and wholesale acquisition costs.ResultsThe FDA approved 206 new drugs in 2017 through 2020, of which 162 (78.6%) were granted marketing authorization by at least 1 other regulatory agency at a median (IQR) delay of 12.1 (17.7) months following US approval. Conversely, 5 FDA-approved drugs were refused marketing authorization by an international regulatory agency due to unfavorable benefit-to-risk assessments. An additional 42 FDA-approved drugs received negative reimbursement recommendations from HTA agencies in Australia, Canada, or the UK due to uncertainty of clinical benefits or unacceptably high prices. The median (IQR) US cost of the 47 drugs refused authorization or not recommended for reimbursement by an international agency was $115 281 ($166 690) per patient per year. Twenty drugs were for oncology indications, and 36 were approved by the FDA through expedited regulatory pathways or the Orphan Drug Act.Conclusions and RelevanceThis cross-sectional study assessed reasons for which drugs recently approved by the FDA were refused marketing authorization or not recommended for public reimbursement in other countries. Drugs with limited international market presence may require close examination by US health care professionals and health systems.

International variation in approval of medicines

“…Researchers used regulatory data for all new medicines approved by the FDA over 4 years from 2017 1. The medicines were matched to regulatory licensing decisions in Australia (Australian Therapeutic Goods Administration), Canada (Health Canada), the European Union (European Medicines Agency) and the UK (Medicines and Healthcare products Regulatory Agency) and public reimbursement decisions made by HTA bodies in Australia (Australian Pharmaceutical Benefits Advisory Committee [APBAC]), Canada (Canadian Agency for Drugs and Technologies in Health [CADTH]) and England (National Institute for Health and Care Excellence [NICE]).…”

“…The FDA licensed 206 new medicines, of which 162 (79%) were licensed by at least one of the regulatory agencies in Australia, Canada, the EU and the UK 1. The median delay between FDA approval and authorisation in one of the other countries was 12 months but the reason for such a delay was not explained.…”

“…Of the FDA-approved medicines, 105 have been assessed by at least one of the three HTA bodies (APBAC, CADTH, NICE) 1. A negative reimbursement recommendation was made for 42 medicines by at least one HTA body; the reasons included uncertain clinical benefit, small comparative clinical benefit, comparative safety concerns and lack of cost-effectiveness.…”

“…The US federal government does not have a national system for assessing cost-effectiveness of new medicines and most FDA-approved medicines are reimbursable by public US programmes 1. Many of the 42 medicines that were not recommended by HTA assessment bodies in Australia, Canada and England were specialist medicines for the treatment of cancer, multiple sclerosis, sleep apnoea and a range of rare conditions.…”

“…Over a 4-year period, the US Food and Drug Administration (FDA) licensed 206 new medicines, of which 162 have been licensed in Australia, Canada, the European Union or the UK 1. However, 42 medicines licensed by the FDA were not approved by a health technology assessment (HTA) body in Australia, Canada or the UK 1…”