Postmarketing safety of orphan drugs: a longitudinal analysis of the US Food and Drug Administration database between 1999 and 2018.

Autor: Fan M; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong., Chan AYL; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.; Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Sha Tin, Hong Kong.; Groningen Research Institute of Pharmacy, Unit of PharmacoTherapy, -Epidemiology and -Economics, University of Groningen, Groningen, The Netherlands., Yan VKC; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong., Tong X; Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong., Lau LKW; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong., Wan EYF; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.; Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong., Tam EYT; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong., Ip P; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong., Lum TY; Department of Social Work and Social Administration, Faculty of Social Sciences, The University of Hong Kong, Pokfulam, Hong Kong., Wong ICK; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong.; Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Sha Tin, Hong Kong.; Research Department of Practice and Policy, UCL School of Pharmacy, London, UK., Li X; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L2-59, 2/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong. sxueli@hku.hk.; Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Sha Tin, Hong Kong. sxueli@hku.hk.; Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong. sxueli@hku.hk.
Jazyk: angličtina
Zdroj: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2022 Jan 04; Vol. 17 (1), pp. 3. Date of Electronic Publication: 2022 Jan 04.
DOI: 10.1186/s13023-021-02166-9
Abstrakt: Background: Information about the specific regulatory environment of orphan drugs is scarce and inconsistent. Uncertainties surrounding the postmarketing long-term safety of orphan drugs remain. This study aimed to evaluate the labelling changes of orphan drugs and to identify postmarketing safety-associated approval factors.
Methods: This retrospective cohort study includes all drugs with orphan drug designation approved by the Center for Drug Evaluation and Research of the US Food and Drug Administration between 1999 and 2018. Main outcomes are safety-related labelling changes up to 31 December 2019. We defined any safety-related labelling changes as postmarketing safety events (PMSE). Safety-related withdrawals, suspensions, and boxed warnings were further categorised as severe postmarketing safety events (SPSE). Outcome measurements include frequencies of PMSE, SPSE, and association between approval factors and the occurrence of safety events.
Results: Amongst the 214 drugs identified with orphan drug designation (25.7% biologics), 83.6% were approved through at least one expedited programme, and 29.4% were approved with boxed warnings. During a median follow-up of 6.74 years since approval, 69.2% and 14.5% of the analysed orphan drugs had PMSE and SPSE, respectively. Safety-related withdrawal (0%, 0/214), suspended marketing (0.46%, 1/214) and new boxed warnings are uncommon (3.7%, 8/214). The safety-related labelling changes were more frequent in the drugs approved with boxed warnings [Incidence rate ratio (IRR): 1.95 (1.02-3.73)] and approved for long-term use [IRR: 2.76 (1.52-5.00)].
Conclusions and Relevance: In this long-term postmarketing analysis, approximately 70% of FDA-approved orphan drugs had safety-related labelling changes although severe safety events were rare. While maintaining early access to orphan drugs, the drug regulatory body has taken timely regulatory action with postmarketing surveillance to ensure patient safety.
(© 2021. The Author(s).)
Databáze: MEDLINE
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