ReviewIntensive care medicine2022
Randomised clinical trials in critical care: past, present and future.
Review in Intensive care medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 7 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
65 citing papers in PubMed, 7 syntheses or guidelines pooled it.
- Challenges and Recommendations for Integrating Circadian Medicine in Critical Care: A Roadmap.Chest · 2026Guideline
- Underreporting of acute kidney injury in randomized trials of acute respiratory distress syndrome with mortality endpoints: a systematic review.Critical care science · 2026Pooled it
- Research without prior consent procedure and intervention effect on mortality in critical care: a meta-epidemiological study of randomized controlled trials.Critical care (London, England) · 2025Pooled it
- Characterization changes and research waste in randomized controlled trials of global gastroesophageal reflux disease and hiatus hernia over the past 20 years.International journal of surgery (London, England) · 2025Pooled it
- Eligibility Criteria of Randomized Clinical Trials in Critical Care Medicine.JAMA network open · 2025Pooled it
- Composite outcome measures in high-impact critical care randomised controlled trials: a systematic review.Critical care (London, England) · 2024Pooled it
- Methodology and design of platform trials: a meta-epidemiological study.Journal of clinical epidemiology · 2023Pooled it
- Trial
- Use of days alive without life support and similar count outcomes in randomised clinical trials - an overview and comparison of methodological choices and analysis methods.BMC medical research methodology · 2023Trial
- Heterogeneous treatment effects of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia-Post hoc exploratory analyses of the COVID STEROID 2 trial.Acta anaesthesiologica Scandinavica · 2023Trial
- Decades of intensive care medicine trials: what randomised evidence has changed, corrected, and still questions to resolve.Intensive care medicine · 2026Review
- Optimizing endpoints in early phase clinical trials of acute respiratory distress syndrome.American journal of respiratory and critical care medicine · 2026Article
- Sample size assumptions, timing asymmetries, and endpoint selection limit the interpretability of the CLEANSE hemoadsorption trial in septic shock.Critical care (London, England) · 2026Article
- Developing a Core Outcome Measurement Set for Adult ICU Patients, the CoreMS-ICU-A Protocol.Acta anaesthesiologica Scandinavica · 2026Article
- Clinical implications of ferroptosis in critical illness: a narrative review.Journal of intensive care · 2026Review
- Barriers to Adopting Evidence From Bayesian Adaptive Clinical Trials in Critical Care: A Randomized Experiment With US Intensivists.CHEST critical care · 2026Article
- Key Features of Contemporary Pilot and Feasibility Trials: Protocol for a Methodological Study.Acta anaesthesiologica Scandinavica · 2026Review
- The Impact of Diet on Long-Term Oncological Outcomes: Investigating Nutritional Mechanisms in Cancer Prevention Management and Prognosis.Nutrients · 2026Review
- Flawed design and selection bias in critical care randomized controlled trials (RCTs): the patient safety risk of the "RCT mimic".Patient safety in surgery · 2025Review
- Potential of biomarker-based enrichment strategies to identify critically ill patients for emerging cell death interventions.Cell death and differentiation · 2025Article
5 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
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Randomised clinical trials (RCTs) are the gold standard for providing unbiased evidence of intervention effects. Here, we provide an overview of the history of RCTs and discuss the major challenges and limitations of current critical care RCTs, including overly optimistic effect sizes; unnuanced conclusions based on dichotomization of results; limited focus on patient-centred outcomes other than mortality; lack of flexibility and ability to adapt, increasing the risk of inconclusive results and limiting knowledge gains before trial completion; and inefficiency due to lack of re-use of trial infrastructure. We discuss recent developments in critical care RCTs and novel methods that may provide solutions to some of these challenges, including a research programme approach (consecutive, complementary studies of multiple types rather than individual, independent studies), and novel design and analysis methods. These include standardization of trial protocols; alternative outcome choices and use of core outcome sets; increased acceptance of uncertainty, probabilistic interpretations and use of Bayesian statistics; novel approaches to assessing heterogeneity of treatment effects; adaptation and platform trials; and increased integration between clinical trials and clinical practice. We outline the advantages and discuss the potential methodological and practical disadvantages with these approaches. With this review, we aim to inform clinicians and researchers about conventional and novel RCTs, including the rationale for choosing one or the other methodological approach based on a thorough discussion of pros and cons. Importantly, the most central feature remains the randomisation, which provides unparalleled restriction of confounding compared to non-randomised designs by reducing confounding to chance.
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.