ReviewPharmacoepidemiology and drug safety2020
Methods for external control groups for single arm trials or long-term uncontrolled extensions to randomized clinical trials.
Review in Pharmacoepidemiology and drug safety, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Considerations for pooling real-world data as a comparator cohort to a single arm trial: a simulation study on assessment of heterogeneity.BMC medical research methodology · 2023Pooled it
- Novel clinical trial design and analytic methods to tackle challenges in therapeutic development in rare diseases.Annals of translational medicine · 2022Trial
- Considerations for the Integration of Clinical Trials and Real-World Data.Clinical pharmacology and therapeutics · 2026Review
- Population PK/PD Modeling and Simulation to Predict the Comparative Long-Term Efficacy of Olokizumab in Rheumatoid Arthritis Patients.Journal of clinical medicine · 2026Article
- Article
- Duchenne Muscular Dystrophy and Delandistrogene Moxeparvovec Gene Therapy in Children: A Systematic Review and Meta-Analysis.Neurology. Genetics · 2026Review
- Combining external placebo-arm data in a prevention trial: effects of cocoa extract supplementation on cardiovascular disease.European journal of epidemiology · 2026Article
- External Control Augmentation Increases Estimates Precision for Finerenone plus Sodium-Glucose Cotransporter-2 Inhibitors.Kidney international reports · 2026Article
- Article
- Effects of a post-acute care management program on subsequent acute care utilization for hospitalized patients discharged to skilled nursing facilities.BMC health services research · 2026Article
- External Comparator Studies: Performance of Four Missing Data-Handling Approaches, Stratified by Four Different Marginal Estimators.Drug safety · 2025Article
- Real-World Data and Causal Machine Learning to Enhance Drug Development.Therapeutic innovation & regulatory science · 2025Review
- Estimating per-protocol effects in external comparator analyses using real-world data.Journal of comparative effectiveness research · 2025Review
- Estimating comparative effectiveness using Single-Arm trials: A challenge in the field of agnosticism.BMC medical research methodology · 2025Article
- An External Control Arm for the Oral Factor XIa Inhibitor Asundexian Phase 2 Trial in Atrial Fibrillation (PACIFIC-AF) Using Electronic Health Records.Cardiology and therapy · 2025Article
- Flexible quantitative bias analysis for unmeasured confounding in subject-level indirect treatment comparisons with proportional hazards violation.BMC medical research methodology · 2025Article
- Synthetic Data in Healthcare and Drug Development: Definitions, Regulatory Frameworks, Issues.CPT: pharmacometrics & systems pharmacology · 2025Review
- Safe inference outside of randomized trials: Application of the stability-controlled quasi-experiment to the effects of three COVID-19 therapies.Observational studies · 2025Article
- Editorial: External control arms for single-arm studies: methodological considerations and applications.Frontiers in drug safety and regulation · 2025Article
- Informative censoring in externally controlled clinical trials: a potential source of bias.ESMO open · 2025Article
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 at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeClinical trials compare outcomes among patients receiving study treatment with comparators drawn from the same source. These internal controls are missing in single arm trials and from long-term extensions (LTE) of trials including only the treatment arm. An external control group derived from a different setting is then required to assess safety or effectiveness.
methodsWe present examples of external control groups that demonstrate some of the issues that arise and make recommendations to address them through careful assessment of the data source fitness for use, design, and analysis steps.
resultsInclusion and exclusion criteria and context that produce a trial population may result in trial patients with different clinical characteristics than are present in an external comparison group. If these differences affect the risk of outcomes, then a comparison of outcome occurrence will be confounded. Further, patients who continue into LTE may differ from those initially entering the trial due to treatment effects. Application of appropriate methods is needed to make valid inferences when such treatment or selection effects are present. Outcome measures in a trial may be ascertained and defined differently from what can be obtained in an external comparison group. Differences in sensitivity and specificity for identification or measurement of study outcomes leads to information bias that can also invalidate inferences.
conclusionThis review concentrates on threats to the valid use of external control groups both in the scenarios of single arm trials and LTE of randomized controlled trials, along with methodological approaches to mitigate them.
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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.