{"title":"Optimal Significance Levels and Sample Sizes for Signal Detection Methods Based on Non-constant Hazards.","authors":"Odile Sauzet, Julia Dyck, Victoria Cornelius","doi":"10.1007/s40264-024-01460-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Statistical methods for signal detection of adverse drug reactions (ADRs) in electronic health records (EHRs) need information about optimal significance levels and sample sizes to achieve sufficient power. Sauzet and Cornelius proposed tests for signal detection based on the hazard functions of Weibull type distributions (WSP tests) which use the time-to-event information available in EHRs. Optimal significance levels and sample sizes for the application of the WPS tests are derived.</p><p><strong>Method: </strong>A simulation study was performed with a range of scenarios for sample size, rate of event due (ADRs), and not due to the drug and random time to ADR occurrence. Based on the area under the curve of the receiver operating characteristic graph, we obtain optimal significance levels of the different WSP tests for the implementation in a hypothesis free signal detection setting and approximate sample sizes required to reach a power of 80% or 90%.</p><p><strong>Results: </strong>The dWSP-pPWSP (combination of double WSP and power WSP) test with a significance level of 0.004 was recommended. Sample sizes needed for a power of 80% were found to start at 60 events for an ADR rate equal to the background rate of 0.1. The number of events required for a background rate of 0.05 and an ADR rate equal to a 20% increase of the background rate was 900.</p><p><strong>Conclusion: </strong>Based on this study, it is recommended to use the dWSP-pWSP test combination for signal detection with a significance level of 0.004 when the same test is applied to all adverse events not depending on rates.</p>","PeriodicalId":11382,"journal":{"name":"Drug Safety","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485065/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Safety","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40264-024-01460-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background and objectives: Statistical methods for signal detection of adverse drug reactions (ADRs) in electronic health records (EHRs) need information about optimal significance levels and sample sizes to achieve sufficient power. Sauzet and Cornelius proposed tests for signal detection based on the hazard functions of Weibull type distributions (WSP tests) which use the time-to-event information available in EHRs. Optimal significance levels and sample sizes for the application of the WPS tests are derived.
Method: A simulation study was performed with a range of scenarios for sample size, rate of event due (ADRs), and not due to the drug and random time to ADR occurrence. Based on the area under the curve of the receiver operating characteristic graph, we obtain optimal significance levels of the different WSP tests for the implementation in a hypothesis free signal detection setting and approximate sample sizes required to reach a power of 80% or 90%.
Results: The dWSP-pPWSP (combination of double WSP and power WSP) test with a significance level of 0.004 was recommended. Sample sizes needed for a power of 80% were found to start at 60 events for an ADR rate equal to the background rate of 0.1. The number of events required for a background rate of 0.05 and an ADR rate equal to a 20% increase of the background rate was 900.
Conclusion: Based on this study, it is recommended to use the dWSP-pWSP test combination for signal detection with a significance level of 0.004 when the same test is applied to all adverse events not depending on rates.
期刊介绍：
Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes:
Overviews of contentious or emerging issues.
Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes.
In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area.
Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement.
Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics.
Editorials and commentaries on topical issues.
Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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