ArticleOrphanet journal of rare diseases2022
Postmarketing safety of orphan drugs: a longitudinal analysis of the US Food and Drug Administration database between 1999 and 2018.
Article in Orphanet journal of rare diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Systematic review protocol on evidence synthesis for health technology decisions in ultra-rare diseases.Systematic reviews · 2026Article
- Evidence available and used by the Food and Drug Administration for the approval of orphan and nonorphan drugs.Health affairs scholar · 2025Article
- Special FDA designations for drug development: orphan, fast track, accelerated approval, priority review, and breakthrough therapy.The European journal of health economics : HEPAC : health economics in prevention and care · 2024Review
- Factors associated with hematological adverse reactions of drugs authorized via the centralized procedure.Scientific reports · 2024Article
- The impact of level of documentation on the accessibility and affordability of new drugs in Norway.Frontiers in pharmacology · 2024Article
- Innovative thinking of clinical investigation for rare disease drug development.Orphanet journal of rare diseases · 2023Review
- FDA approval, clinical trial evidence, efficacy, epidemiology, and price for non-orphan and ultra-rare, rare, and common orphan cancer drug indications: cross sectional analysis.BMJ (Clinical research ed.) · 2023Article
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Authors and funding
11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundInformation 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.
methodsThis 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.
resultsAmongst 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.
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