ReviewThe Lancet. Respiratory medicine2022
Use of pragmatic and explanatory trial designs in acute care research: lessons from COVID-19.
Review in The Lancet. Respiratory medicine, 2022. 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 24 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
24 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Challenges and Recommendations for Integrating Circadian Medicine in Critical Care: A Roadmap.Chest · 2026Guideline
- A rapid review of community engagement and informed consent processes for adaptive platform trials and alternative design trials for public health emergencies.Wellcome open research · 2023Pooled it
- Contextual factors related to ventilator mode during an embedded randomized trial: a longitudinal survey of clinicians.BMC health services research · 2026Trial
- Trial
- Oral Melatonin in Critically Ill Patients With COVID-19: A Quasi-Experimental Pragmatic Trial.Journal of medical virology · 2026Trial
- Measles, mumps, and rubella vaccine at age 6 months and hospitalisation for infection before age 12 months: randomised controlled trial.BMJ (Clinical research ed.) · 2023Trial
- Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial.BMC research notes · 2023Trial
- A framework for health systems to assess and prioritize participation in pragmatic clinical trials.Learning health systems · 2025Article
- Eliciting Patient Preferences for Pragmatic Critical Care Trials: A Qualitative Study.Annals of the American Thoracic Society · 2025Article
- Co-designing and pilot-testing an infographic to support the consent process in an adaptive platform trial for adults in ICU with community-acquired pneumonia or COVID-19: a mixed methods study within a trial (SWAT).Research involvement and engagement · 2025Article
- Review
- Cultivating Innovative, Pragmatic, Randomized Controlled Registry Trials Embedded in Hemodialysis Care: Conference Proceeding From Gardener's Grove 2023.Canadian journal of kidney health and disease · 2025Article
- Toward Precision in Critical Care Research: Methods for Observational and Interventional Studies.Critical care medicine · 2024Review
- Candent issues in pneumonia. Reflections from the Fifth Annual Meeting of Spanish Experts 2023.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2024Review
- Insights into epileptogenesis from post-traumatic epilepsy.Nature reviews. Neurology · 2024Review
- Research Priorities in Critical Care Cardiology: JACC Expert Panel.Journal of the American College of Cardiology · 2023Review
- Designing and Implementing "Living and Breathing" Clinical Trials: An Overview and Lessons Learned from the COVID-19 Pandemic.Critical care clinics · 2023Review
- Progressing from "Whether to" to "How to" Conduct Pragmatic Trials.The American journal of bioethics : AJOB · 2023Article
- Preoxygenation with standard facemask combining apnoeic oxygenation using high flow nasal cannula versuss standard facemask alone in patients with and without obesity: the OPTIMASK international study.Annals of intensive care · 2023Article
- Optimizing patient recruitment into clinical trials of antimicrobial-resistant pathogens.JAC-antimicrobial resistance · 2023Review
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
19 authors.
Funding
Abstract
Unique challenges arise when conducting trials to evaluate therapies already in common clinical use, including difficulty enrolling patients owing to widespread open-label use of trial therapies and the need for large sample sizes to detect small but clinically meaningful treatment effects. Despite numerous successes in trials evaluating novel interventions such as vaccines, traditional explanatory trials have struggled to provide definitive answers to time-sensitive questions for acutely ill patients with COVID-19. Pragmatic trials, which can increase efficiency by allowing some or all trial procedures to be embedded into clinical care, are increasingly proposed as a means to evaluate therapies that are in common clinical use. In this Personal View, we use two concurrently conducted COVID-19 trials of hydroxychloroquine (the US ORCHID trial and the UK RECOVERY trial) to contrast the effects of explanatory and pragmatic trial designs on trial conduct, trial results, and the care of patients managed outside of clinical trials. In view of the potential advantages and disadvantages of explanatory and pragmatic trial designs, we make recommendations for their optimal use in the evaluation of therapies in the acute care setting.
Indexed as
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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.