ArticleDrug safety2012
A signal detection method to detect adverse drug reactions using a parametric time-to-event model in simulated cohort data.
Article in Drug safety, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Mavacamten and atrial fibrillation: assessing the risk through FAERS and meta-analysis.BMC cardiovascular disorders · 2026Pooled it
- Pharmacovigilance and network toxicology analysis of risdiplam-associated adverse events in pediatric patients with spinal muscular atrophy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Post-Marketing Safety Profile of Mirikizumab: A Multi-Database Pharmacovigilance Study Using FAERS and JADER with IL-23 Inhibitor Class Comparison.Bioengineering (Basel, Switzerland) · 2026Article
- Pharmacovigilance study of INSTIs associated with weight gain and glucose/lipid metabolism adverse events based on the FDA adverse event reporting system.HIV medicine · 2026Article
- Stratified Therapeutic Drug Monitoring Could Potentially Improve the Efficacy and Safety of Oxcarbazepine in Children with Epilepsy: Novel Insights from a Single-Center, Large-Sample, Retrospective Real-World Study.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Male sexual dysfunction associated with TNF-α inhibitors: an indication-stratified global pharmacovigilance analysis.Frontiers in pharmacology · 2026Article
- Safety evaluation of deucravacitinib: a real-world analysis based on the FDA adverse event reporting system database.International journal of clinical pharmacy · 2025Article
- Evaluation of the real-world safety of Canakinumab in the treatment of systemic juvenile idiopathic arthritis in children aged 0-16: a comprehensive analysis based on FAERS data.Pediatric rheumatology online journal · 2025Article
- Postmarketing adverse events of efgartigimod alfa: a real-world pharmacovigilance study based on the FAERS database.BMJ open · 2025Article
- A disproportionality analysis of adverse events associated with ertapenem using the FAERS database from 2004 to 2024.Scientific reports · 2025Article
- Adverse drug reactions to atezolizumab in combination with bevacizumab in hepatocellular carcinoma patients: an analysis of the food and drug administration adverse event reporting system database.Frontiers in pharmacology · 2025Article
- Safety assessment of sodium zirconium cyclosilicate: A FAERS-based disproportionality analysis.PloS one · 2025Article
- Characterization of ocular adverse events associated with crizotinib: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase.Frontiers in oncology · 2025Article
- Optimal Significance Levels and Sample Sizes for Signal Detection Methods Based on Non-constant Hazards.Drug safety · 2024Article
- Evaluation of tolvaptan-associated hepatic disorder using different national pharmacovigilance databases.Scientific reports · 2024Article
- Neurological and Psychiatric Adverse Events Associated with Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer Patients: Insights from a Pharmacovigilance Study via the FDA Adverse Event Reporting System.Clinical drug investigation · 2024Article
- Long-term hepatobiliary disorder associated with trastuzumab emtansine pharmacovigilance study using the FDA Adverse Event Reporting System database.Scientific reports · 2024Article
- Spectrum of psychiatric adverse reactions to cyclin-dependent kinases 4/6 inhibitors: A pharmacovigilance analysis of the FDA adverse event reporting system.CNS neuroscience & therapeutics · 2024Article
- Post-marketing safety concerns of sotorasib: A disproportionality analysis based on FDA adverse event reporting system.Heliyon · 2024Article
- A real-world pharmacovigilance analysis for transthyretin inhibitors: findings from the FDA adverse event reporting database.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrent quantitative signal detection methods have been primarily developed for the purpose of detecting signals from spontaneous reports. These methods are not always appropriate for cohort data. More recently, parametric time-to-event models have been proposed to model hazard functions with the ultimate aim of detecting adverse drug reactions (ADRs). The rate of occurrence of ADRs after starting a drug will depend upon the causal mechanism and therefore will often vary with time, in contrast to events not associated with the drug, which will tend to occur at a constant background rate. After starting treatment, the onset of ADRs will be rapid for some but delayed for others. A non-constant rate over time may indicate a drug-event relationship.
objectiveThe aim of this study was to propose a simple test to detect signals of ADRs in cohort data and to investigate the power of this test using simulated data. A signal detection tool using the proposed test to improve the power of detection is also described.
methodIn order to test for a non-constant hazard (rate of occurrence), the hazard function was estimated using the model shape parameter for the Weibull function. If the shape parameter was found to be significantly different (p < 0.05) from the value one (the value for a constant hazard) a signal was raised. Simulation of background event rates used were 1%, 5% and 10% of the cohort size. The ADR rate was varied in proportion to the background rate; a 10%, 20% and 50% increase in the background rate was explored. The time of occurrence of the ADR will dictate the shape of the hazard function, therefore the ability of the model to detect a signal depending when the highest risk for ADR was also explored. The power of the test was investigated by simulation.
resultsThe Weibull Shape Parameter (WSP) test was most powerful at detecting signals that occur shortly after starting treatment. These preliminary simulations had low power when the underlying hazard function was symmetrical (e.g. when ADRs occurred in the middle of the study period). The power of the test was improved by censoring the data as this broke the symmetry of the hazard function. A tool that censored the data at regular intervals and repeated the WSP test was found to correctly detect ADR or no ADR around 90% of the time when the sample size was at least 5000.
conclusionThe WSP test is simple to implement using standard statistical software, and can be used to detect non-constant hazards over time in order to raise signals of time-dependent ADRs. When there is no pre-specified event of interest or the time of the ADR is uncertain, the WSP tool should be used instead of the WSP test. These methods do not require any external data for comparative purposes and thus can be implemented in a single cohort of participants exposed to a drug.
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