ArticleDrug safety2013
Post-approval safety issues with innovative drugs: a European cohort study.
Article in Drug safety, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis.BMJ quality & safety · 2022Pooled it
- Cytopenias as Adverse Drug Reactions: A 10-Year Analysis of Reporting Structure, Rate, and Trend.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Factors associated with hematological adverse reactions of drugs authorized via the centralized procedure.Scientific reports · 2024Article
- Distribution- and Metabolism-Based Drug Discovery: A Potassium-Competitive Acid Blocker as a Proof of Concept.Research (Washington, D.C.) · 2022Article
- The Impact of Variability in Patient Exposure During Premarket Clinical Development on Postmarket Safety Outcomes.Clinical pharmacology and therapeutics · 2021Article
- Critical Considerations for the Design of Multi-Organ Microphysiological Systems (MPS).Frontiers in cell and developmental biology · 2021Review
- Postmarketing Safety-Related Regulatory Actions for New Therapeutic Biologics Approved in the United States 2002-2014: Similarities and Differences With New Molecular Entities.Clinical pharmacology and therapeutics · 2020Article
- Safety-Related Regulatory Actions and Risk Factors for Anticancer Drugs in Japan.Pharmaceutical medicine · 2019Article
- Human-Derived Organ-on-a-Chip for Personalized Drug Development.Current pharmaceutical design · 2018Review
- Registries supporting new drug applications.Pharmacoepidemiology and drug safety · 2017Article
- Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-ToxArchives of toxicology · 2017Article
- Analysis of Safety-Related Regulatory Actions for New Drugs in Japan by Nature of Identified Risks.Pharmaceutical medicine · 2017Article
- A description of signals during the first 18 months of the EMA pharmacovigilance risk assessment committee.Drug safety · 2014Article
- Profiling of drugs and environmental chemicals for functional impairment of neural crest migration in a novel stem cell-based test battery.Archives of toxicology · 2014Article
- Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells.Chemical research in toxicology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAt time of approval, knowledge of the full benefit risk of any drug is limited, in particular with regards to safety. Post-approval surveillance of potential drug safety concerns is recognized as an important task of regulatory agencies. For innovative, often first-in-class drugs, safety knowledge at time of approval is often even less extensive and these may require tighter scrutiny post approval.
objectiveWe evaluated whether more post-approval serious safety issues were identified for drugs with a higher level of innovation.
methodsA cohort study was performed that included all new active substances approved under the European Centralized Procedure and for which serious safety issues were identified post-approval from 1 January 1999 to 1 January 2012. Serious safety issues were defined as issues requiring a Direct Healthcare Professional Communication to alert individual healthcare professionals of a new serious safety issue, or a safety-related drug withdrawal. Data were retrieved from publicly available websites of the Dutch Medicines Evaluation Board and the European Medicines Agency. The level of innovation was scored using a validated algorithm, grading drugs as important (A), moderate (B) or modest (C) innovations or as pharmacological or technological (pharm/tech) innovations. The data were analyzed using appropriate descriptive statistics and Kaplan-Meier analysis, with a Mantel-Cox log-rank test, and Cox-regression models correcting for follow-up duration, to identify a possible trend in serious safety issues with an increasing level of innovation.
resultsIn Europe, 279 new drugs were approved between 1999 and 2011. Fifty-nine (21 %) were graded as important, 63 (23 %) moderate, or 34 (12 %) modest innovations and 123 (44 %) as non-innovative (pharm/tech), while 15 (25 %), 13 (21 %), 8 (24 %) and 17 (14 %) had post-approval safety issues, respectively (p = 0.06, linear-by-linear test). Five drugs were withdrawn from the market. The Kaplan-Meier-derived probability for having a first serious safety issue was statistically significant, log-rank (Mantel-Cox) p = 0.036. In the final adjusted Cox proportional hazard model there was no statistically significant difference in occurrence of a first serious safety issue for important, moderate and modest innovations versus non-innovative drugs; hazard ratios 1.76 (95 % CI 0.82-3.77), 1.61 (95 % CI 0.76-3.41)], and 1.25 (95 % CI 0.51-3.06), respectively.
conclusionA higher level of innovation was not clearly related to an increased risk of serious safety issues identified after approval.
Indexed as
Identifiers
24048690What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.