SynthesisDrug safety2013
Defining a reference set to support methodological research in drug safety.
Synthesis in Drug safety, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 2 of them syntheses 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
86 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Methods for drug safety signal detection using routinely collected observational electronic health care data: A systematic review.Pharmacoepidemiology and drug safety · 2023Pooled it
- Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D).Diabetes, obesity & metabolism · 2018 · on this mapPooled it
- Contrastive learning of adverse events to provide effective and interpretable vector representations for machine-assisted pharmacovigilance.Briefings in bioinformatics · 2026Article
- Negative controls and how to use them: a guidance paper.International journal of epidemiology · 2026Article
- Causal knowledge graph analysis identifies adverse drug effects.Bioinformatics (Oxford, England) · 2026Article
- Review
- Recommendations to Enable Broader Use of Real-World Evidence to Inform Decision-Making Throughout Pharmacovigilance Signal Management.Pharmacoepidemiology and drug safety · 2025Review
- Article
- A trajectory-informed model for detecting drug-drug-host interaction from real-world data.Journal of biomedical informatics · 2025Article
- A theoretical model for detecting drug interaction with awareness of timing of exposure.Scientific reports · 2025Article
- Probing Large Language Model Hidden States for Adverse Drug Reaction Knowledge.medRxiv : the preprint server for health sciences · 2025Article
- Applying two approaches to detect unmeasured confounding due to time-varying variables in a self-controlled risk interval design evaluating COVID-19 vaccine safety signals, using myocarditis as a case example.American journal of epidemiology · 2025Article
- Cell-type specific single-cell signatures reveal nephrotoxic drug effects.Computational and structural biotechnology journal · 2025Article
- The State of Use and Utility of Negative Controls in Pharmacoepidemiologic Studies.American journal of epidemiology · 2024Review
- Using public clinical trial reports to probe non-experimental causal inference methods.BMC medical research methodology · 2023Article
- Exploring the impact of design criteria for reference sets on performance evaluation of signal detection algorithms: The case of drug-drug interactions.Pharmacoepidemiology and drug safety · 2023Article
- Early Detection of Adverse Drug Reaction Signals by Association Rule Mining Using Large-Scale Administrative Claims Data.Drug safety · 2023Article
- The Coming of Age of AI/ML in Drug Discovery, Development, Clinical Testing, and Manufacturing: The FDA Perspectives.Drug design, development and therapy · 2023Article
- Evaluation of four machine learning models for signal detection.Therapeutic advances in drug safety · 2023Article
- Using a data-driven approach for the development and evaluation of phenotype algorithms for systemic lupus erythematosus.PloS one · 2023Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMethodological research to evaluate the performance of methods requires a benchmark to serve as a referent comparison. In drug safety, the performance of analyses of spontaneous adverse event reporting databases and observational healthcare data, such as administrative claims and electronic health records, has been limited by the lack of such standards.
objectivesTo establish a reference set of test cases that contain both positive and negative controls, which can serve the basis for methodological research in evaluating methods performance in identifying drug safety issues. RESEARCH
designSystematic literature review and natural language processing of structured product labeling was performed to identify evidence to support the classification of drugs as either positive controls or negative controls for four outcomes: acute liver injury, acute kidney injury, acute myocardial infarction, and upper gastrointestinal bleeding.
resultsThree-hundred and ninety-nine test cases comprised of 165 positive controls and 234 negative controls were identified across the four outcomes. The majority of positive controls for acute kidney injury and upper gastrointestinal bleeding were supported by randomized clinical trial evidence, while the majority of positive controls for acute liver injury and acute myocardial infarction were only supported based on published case reports. Literature estimates for the positive controls shows substantial variability that limits the ability to establish a reference set with known effect sizes.
conclusionsA reference set of test cases can be established to facilitate methodological research in drug safety. Creating a sufficient sample of drug-outcome pairs with binary classification of having no effect (negative controls) or having an increased effect (positive controls) is possible and can enable estimation of predictive accuracy through discrimination. Since the magnitude of the positive effects cannot be reliably obtained and the quality of evidence may vary across outcomes, assumptions are required to use the test cases in real data for purposes of measuring bias, mean squared error, or coverage probability.
Indexed as
Identifiers
24166222What 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.