ArticleJournal of the American Medical Informatics Association : JAMIA2020
Large-scale evidence generation and evaluation across a network of databases (LEGEND): assessing validity using hypertension as a case study.
Article in Journal of the American Medical Informatics Association : JAMIA, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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
21 citing papers in PubMed.
- Post-Acute Dyslipidemia and Abnormal Body Mass Index in Children and Adolescents with COVID-19: A Cohort Study from the RECOVER Initiative.The Journal of pediatrics · 2026Article
- Post-acute dyslipidemia and abnormal BMI in children and adolescents with COVID-19: An EHR Cohort Study from the RECOVER Initiative.medRxiv : the preprint server for health sciences · 2025Article
- Objective study validity diagnostics: a framework requiring pre-specified, empirical verification to increase trust in the reliability of real-world evidence.Journal of the American Medical Informatics Association : JAMIA · 2025Article
- Pediatric Gastrointestinal Tract Outcomes During the Postacute Phase of COVID-19.JAMA network open · 2025Article
- Application of a digital quality measure for cancer diagnosis in Epic Cosmos.Journal of the American Medical Informatics Association : JAMIA · 2025Article
- Pediatric Gastrointestinal Outcomes During the Post-Acute Phase of COVID-19: Findings from RECOVER Initiative from 29 Hospitals in the US.medRxiv : the preprint server for health sciences · 2024Article
- OHDSI Standardized Vocabularies-a large-scale centralized reference ontology for international data harmonization.Journal of the American Medical Informatics Association : JAMIA · 2024Article
- LEVERAGING EPIC'S NATIVE ETL INFRASTRUCTURE FOR OMOP CDM IMPLEMENTATION: A COLLABORATIVE EXPERIENCE.AMIA ... Annual Symposium proceedings. AMIA Symposium · 2024Article
- Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM.BMJ medicine · 2023Article
- Prior-Preconditioned Conjugate Gradient Method for Accelerated Gibbs Sampling in "LargeJournal of the American Statistical Association · 2023Article
- Adjusting for indirectly measured confounding using large-scale propensity score.Journal of biomedical informatics · 2022Article
- Assessing the effectiveness of empirical calibration under different bias scenarios.BMC medical research methodology · 2022Article
- Article
- Analysis of Dual Combination Therapies Used in Treatment of Hypertension in a Multinational Cohort.JAMA network open · 2022Article
- International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients.Frontiers in pharmacology · 2022Article
- Data Consult Service: Can we use observational data to address immediate clinical needs?Journal of the American Medical Informatics Association : JAMIA · 2021Article
- Increasing trust in real-world evidence through evaluation of observational data quality.Journal of the American Medical Informatics Association : JAMIA · 2021Article
- Drawing Reproducible Conclusions from Observational Clinical Data with OHDSI.Yearbook of medical informatics · 2021Article
- Comprehensive Comparative Effectiveness and Safety of First-Line β-Blocker Monotherapy in Hypertensive Patients: A Large-Scale Multicenter Observational Study.Hypertension (Dallas, Tex. : 1979) · 2021Observational
- Inflection Point: Ideas for Accelerating Breakthroughs and Improving Cardiovascular Health.Circulation. Cardiovascular quality and outcomes · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
Abstract
objectivesTo demonstrate the application of the Large-scale Evidence Generation and Evaluation across a Network of Databases (LEGEND) principles described in our companion article to hypertension treatments and assess internal and external validity of the generated evidence. MATERIALS AND
methodsLEGEND defines a process for high-quality observational research based on 10 guiding principles. We demonstrate how this process, here implemented through large-scale propensity score modeling, negative and positive control questions, empirical calibration, and full transparency, can be applied to compare antihypertensive drug therapies. We assess internal validity through covariate balance, confidence-interval coverage, between-database heterogeneity, and transitivity of results. We assess external validity through comparison to direct meta-analyses of randomized controlled trials (RCTs).
resultsFrom 21.6 million unique antihypertensive new users, we generate 6 076 775 effect size estimates for 699 872 research questions on 12 946 treatment comparisons. Through propensity score matching, we achieve balance on all baseline patient characteristics for 75% of estimates, observe 95.7% coverage in our effect-estimate 95% confidence intervals, find high between-database consistency, and achieve transitivity in 84.8% of triplet hypotheses. Compared with meta-analyses of RCTs, our results are consistent with 28 of 30 comparisons while providing narrower confidence intervals.
conclusionWe find that these LEGEND results show high internal validity and are congruent with meta-analyses of RCTs. For these reasons we believe that evidence generated by LEGEND is of high quality and can inform medical decision-making where evidence is currently lacking. Subsequent publications will explore the clinical interpretations of this evidence.
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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.