ReviewAmerican journal of respiratory and critical care medicine2016
Toward Smarter Lumping and Smarter Splitting: Rethinking Strategies for Sepsis and Acute Respiratory Distress Syndrome Clinical Trial Design.
Review in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 3 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
192 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Do Interventions Improve Symptoms Among ICU Surrogates Facing End-of-Life Decisions? A Prognostically-Enriched Systematic Review and Meta-Analysis.Critical care medicine · 2022Pooled it
- A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality.Critical care (London, England) · 2020Pooled it
- Guidelines on the management of acute respiratory distress syndrome.BMJ open respiratory research · 2019Guideline
- Early differential protein expression in blood and bronchoalveolar fluid among ARDS phenotypes.Scientific reports · 2026Trial
- Development and validation of novel sepsis subphenotypes using trajectories of vital signs.Intensive care medicine · 2022Trial
- Clustering identifies endotypes of traumatic brain injury in an intensive care cohort: a CENTER-TBI study.Critical care (London, England) · 2022Trial
- Identification of phenotypes in paediatric patients with acute respiratory distress syndrome: a latent class analysis.The Lancet. Respiratory medicine · 2022Trial
- Trial
- Adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation.Genes and immunity · 2019Trial
- Trial
- Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study.Intensive care medicine · 2018Trial
- Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis.Thorax · 2018Trial
- Trial
- Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial.American journal of respiratory and critical care medicine · 2017Trial
- Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome.Critical care medicine · 2017Trial
- Early Immune Phenotype-Guided Immunomodulatory Strategies and Intensive Care Outcomes in Septic Shock: A Single-Center Retrospective Cohort Study.Shock (Augusta, Ga.) · 2026Observational
- Multi-cohort consensus clustering identifies three distinct transcriptomic endotypes in sepsis.BMC bioinformatics · 2026Article
- Predictive validity of SOFA-2: analytical and contextual considerations.Critical care (London, England) · 2026Article
- Whole blood transcriptomics reveals sepsis mortality-associated changes in neutrophil degranulation.American journal of respiratory cell and molecular biology · 2026Observational
- Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS.Critical care (London, England) · 2026Observational
132 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
5 authors.
Funding
Abstract
Both quality improvement and clinical research efforts over the past few decades have focused on consensus definition of sepsis and acute respiratory distress syndrome (ARDS). Although clinical definitions based on readily available clinical data have advanced recognition and timely use of broad supportive treatments, they likely hinder the identification of more targeted therapies that manipulate select biological mechanisms underlying critical illness. Sepsis and ARDS are by definition heterogeneous, and patients vary in both their underlying biology and their severity of illness. We have long been able to identify subtypes of sepsis and ARDS that confer different prognoses. The key is that we are now on the verge of identifying subtypes that may confer different response to therapy. In this perspective, inspired by a 2015 American Thoracic Society International Conference Symposium entitled "Lumpers and Splitters: Phenotyping in Critical Illness," we highlight promising approaches to uncovering patient subtypes that may predict treatment responsiveness and not just differences in prognosis. We then discuss how this information can be leveraged to improve the success and translatability of clinical trials by using predictive enrichment and other design strategies. Last, we discuss the challenges and limitations to identifying biomarkers and endotypes and incorporating them into routine clinical practice.
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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.