ReviewDrug safety2022
A Review of Causal Inference for External Comparator Arm Studies.
Review in Drug safety, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis 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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Acceptance of external control arms by HTA agencies: a review of oncology submissions in France, England, Germany and Norway from 2021 to 2023.British journal of cancer · 2025Pooled it
- External Control Arms in Japan: A Systematic Case Analysis of Documented Regulatory Implementation and Uncertainty Management.Clinical pharmacology and therapeutics · 2026Article
- AI-based augmentation of oncology clinical trials.Nature reviews. Clinical oncology · 2026Review
- Causal inference in real-world dementia research: a systematic review protocol.Systematic reviews · 2026Article
- Assessing Overall Survival Benefits in Advanced Cancers: The Role of External Comparator Cohort Studies with Real-World Data.Clinical pharmacology and therapeutics · 2026Article
- Article
- Sieving for gold: external comparator studies to prioritize drugs for late-stage clinical trial.Journal of comparative effectiveness research · 2026Review
- External Comparator Studies: Performance of Four Missing Data-Handling Approaches, Stratified by Four Different Marginal Estimators.Drug safety · 2025Article
- Examining the Effect of Missing Data and Unmeasured Confounding on External Comparator Studies: Case Studies and Simulations.Drug safety · 2024Article
- A federated learning system for precision oncology in Europe: DigiONE.Nature medicine · 2024Article
- Application of the target trial emulation framework to external comparator studies.Frontiers in drug safety and regulation · 2024Article
- External comparator studies and the joint application of the estimand and target trial emulation frameworks.Frontiers in drug safety and regulation · 2024Article
- Important tool in our rare disease toolbox: hybrid retrospective-prospective natural history studies serve well as external comparators for rare disease studies.Frontiers in drug safety and regulation · 2024Review
- Utilization of anonymization techniques to create an external control arm for clinical trial data.BMC medical research methodology · 2023Observational
- Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Review
- External comparators and estimands.Frontiers in drug safety and regulation · 2023Article
- External Comparator Cohort studies - clarification of terminology.Frontiers in drug safety and regulation · 2023Article
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 at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Randomized controlled trials (RCTs) are the gold standard design to establish the efficacy of new drugs and to support regulatory decision making. However, a marked increase in the submission of single-arm trials (SATs) has been observed in recent years, especially in the field of oncology due to the trend towards precision medicine contributing to the rise of new therapeutic interventions for rare diseases. SATs lack results for control patients, and information from external sources can be compiled to provide context for better interpretability of study results. External comparator arm (ECA) studies are defined as a clinical trial (most commonly a SAT) and an ECA of a comparable cohort of patients-commonly derived from real-world settings including registries, natural history studies, or medical records of routine care. This publication aims to provide a methodological overview, to sketch emergent best practice recommendations and to identify future methodological research topics. Specifically, existing scientific and regulatory guidance for ECA studies is reviewed and appropriate causal inference methods are discussed. Further topics include sample size considerations, use of estimands, handling of different data sources regarding differential baseline covariate definitions, differential endpoint measurements and timings. In addition, unique features of ECA studies are highlighted, specifically the opportunity to address bias caused by unmeasured ECA covariates, which are available in the SAT.
Indexed as
Identifiers
What 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.