ArticleAmerican journal of respiratory and critical care medicine2015
Implications of Heterogeneity of Treatment Effect for Reporting and Analysis of Randomized Trials in Critical Care.
Article in American journal of respiratory and critical care medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 7 of them syntheses 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.
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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
153 citing papers in PubMed, 7 syntheses or guidelines pooled it.
- Predictive enrichment using biomarkers in studies of critically-ill patients with sepsis: a systematic review.Critical care (London, England) · 2025Pooled it
- Acetate- versus lactate-buffered crystalloid solutions: A systematic review with meta-analysis and trial sequential analysis.Acta anaesthesiologica Scandinavica · 2022Pooled it
- Between-trial heterogeneity in ARDS research.Intensive care medicine · 2021Pooled it
- Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT.Health technology assessment (Winchester, England) · 2021Pooled it
- Optimal Positive End Expiratory Pressure Levels in Ventilated Patients Without Acute Respiratory Distress Syndrome: A Bayesian Network Meta-Analysis and Systematic Review of Randomized Controlled Trials.Frontiers in medicine · 2021Pooled it
- Predictors of gastrointestinal bleeding in adult ICU patients: a systematic review and meta-analysis.Intensive care medicine · 2019Pooled it
- Measuring and Analyzing Length of Stay in Critical Care Trials.Medical care · 2019Pooled it
- Individualised treatment effects of enhanced early mobilisation in mechanically ventilated patients: a secondary analysis of the TEAM trial.Intensive care medicine · 2026Trial
- Arousal threshold modifies the effect of CPAP on executive function among individuals with obstructive sleep apnoea.The European respiratory journal · 2025Trial
- 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
- Heterogeneity of Treatment Effect in a Randomized Trial of a Communication Intervention.Journal of pain and symptom management · 2022Trial
- Identification of phenotypes in paediatric patients with acute respiratory distress syndrome: a latent class analysis.The Lancet. Respiratory medicine · 2022Trial
- Lower versus higher oxygenation targets in critically ill patients with severe hypoxaemia: secondary Bayesian analysis to explore heterogeneous treatment effects in the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial.British journal of anaesthesia · 2022Trial
- Effect of Esophageal Pressure-guided Positive End-Expiratory Pressure on Survival from Acute Respiratory Distress Syndrome: A Risk-based and Mechanistic Reanalysis of the EPVent-2 Trial.American journal of respiratory and critical care medicine · 2021Trial
- Trial
- Risk Factors for Cardiovascular Collapse during Tracheal Intubation of Critically III Adults.Annals of the American Thoracic Society · 2020Trial
- A Detoxification Intervention for Gulf War Illness: A Pilot Randomized Controlled Trial.International journal of environmental research and public health · 2019Trial
- Trial
- 24 vs. 72 hours of hypothermia for pediatric cardiac arrest: A pilot, randomized controlled trial.Resuscitation · 2018Trial
- Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial.American journal of respiratory and critical care medicine · 2017Trial
93 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
Randomized clinical trials (RCTs) are conducted to guide clinicians' selection of therapies for individual patients. Currently, RCTs in critical care often report an overall mean effect and selected individual subgroups. Yet work in other fields suggests that such reporting practices can be improved. Specifically, this Critical Care Perspective reviews recent work on so-called "heterogeneity of treatment effect" (HTE) by baseline risk and extends that work to examine its applicability to trials of acute respiratory failure and severe sepsis. Because patients in RCTs in critical care medicine-and patients in intensive care units-have wide variability in their risk of death, these patients will have wide variability in the absolute benefit that they can derive from a given therapy. If the side effects of the therapy are not perfectly collinear with the treatment benefits, this will result in HTE, where different patients experience quite different expected benefits of a therapy. We use simulations of RCTs to demonstrate that such HTE could result in apparent paradoxes, including: (1) positive trials of therapies that are beneficial overall but consistently harm or have little benefit to low-risk patients who met enrollment criteria, and (2) overall negative trials of therapies that still consistently benefit high-risk patients. We further show that these results persist even in the presence of causes of death unmodified by the treatment under study. These results have implications for reporting and analyzing RCT data, both to better understand how our therapies work and to improve the bedside applicability of RCTs. We suggest a plan for measurement in future RCTs in the critically ill.
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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.