ArticleEpidemiology (Cambridge, Mass.)2019
Comparison of Self-controlled Designs for Evaluating Outcomes of Drug-Drug Interactions: Simulation Study.
Article in Epidemiology (Cambridge, Mass.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Introduction to case-crossover study design for drug-drug interaction.Annals of clinical epidemiology · 2026Article
- Medications Associated with Increased Risk of Hypoglycemia in Older Adults on Sulfonylureas: A High-Throughput Case-Crossover-Based Screening Study.Drug safety · 2026Article
- Opioid Use After Hip Fracture and Subsequent Fracture Outcomes: A Self-Controlled Case Series Design.Pharmacoepidemiology and drug safety · 2025Article
- Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.Pharmacoepidemiology and drug safety · 2025Review
- Core Concepts: Self-Controlled Designs in Pharmacoepidemiology.Pharmacoepidemiology and drug safety · 2025Review
- Cholinesterase Inhibitor Initiation Does Not Increase the Risk of Fall-Related Injury in Older Adults Treated With Beta-Blockers: A Self-Controlled Case Series Design.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Risk of neuropsychiatric adverse events associated with montelukast use in children and adolescents: a population-based case-crossover study.BMJ paediatrics open · 2024Article
- Thinking Three-Dimensionally: A Self- and Externally-Controlled Approach to Screening for Drug-Drug-Drug Interactions Among High-Risk Populations.Clinical pharmacology and therapeutics · 2024Article
- Breaking Research Silos and Stimulating "Innovation at the Edges" in Epidemiology.American journal of epidemiology · 2023Article
- Continued potassium supplementation use following loop diuretic discontinuation in older adults: An evaluation of a prescribing cascade relic.Journal of the American Geriatrics Society · 2023Article
- Potentially clinically significant drug-drug interactions in older patients admitted to the hospital: A cross-sectional study.Frontiers in pharmacology · 2023Article
- Identifying Clinically Relevant Drug-Drug Interactions With Methadone and Buprenorphine: A Translational Approach to Signal Detection.Clinical pharmacology and therapeutics · 2022Article
- Drug-Drug Interaction Surveillance Study: Comparing Self-Controlled Designs in Five Empirical Examples in Real-World Data.Clinical pharmacology and therapeutics · 2021Article
- Response to "The Self-Controlled Case Series Design as a Viable Alternative to Studying Clinically Relevant Drug Interactions".Clinical pharmacology and therapeutics · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundSelf-controlled designs, both case-crossover and self-controlled case series, are well suited for evaluating outcomes of drug-drug interactions in electronic healthcare data. Their comparative performance in this context, however, is unknown.
methodsWe simulated cohorts of patients exposed to two drugs: a chronic drug (object) and a short-term drug (precipitant) with an associated interaction of 2.0 on the odds ratio scale. We analyzed cohorts using case-crossover and self-controlled case series designs evaluating exposure to the precipitant drug within person-time exposed to the object drug. Scenarios evaluated violations of key design assumptions: (1) time-varying, within-person confounding; (2) time trend in precipitant drug exposure prevalence; (3) nontransient precipitant exposure; and (4) event-dependent object drug discontinuation.
resultsCase-crossover analysis produced biased estimates when 30% of patients persisted on the precipitant drug (estimated OR 2.85) and when the use of the precipitant drug was increasing in simulated cohorts (estimated OR 2.56). Self-controlled case series produced biased estimates when patients discontinued the object drug following the occurrence of an outcome (estimated incidence ratio [IR] of 2.09 [50% of patients stopping therapy] and 2.22 [90%]). Both designs yielded similarly biased estimates in the presence of time-varying, within-person confounding.
conclusionIn settings with independent or rare outcomes and no substantial event-dependent censoring (<50%), self-controlled case series may be preferable to case-crossover design for evaluating outcomes of drug-drug interactions. With frequent event-dependent drug discontinuation, a case-crossover design may be preferable provided there are no time-related trends in drug exposure.
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