ArticleInjury2015
Collider bias in trauma comparative effectiveness research: the stratification blues for systematic reviews.
Article in Injury, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The effectiveness of prehospital hypertonic saline for hypotensive trauma patients: a systematic review and meta-analysis.BMC emergency medicine · 2017Pooled it
- Causal inference methods for systematic reviews.Journal of the Medical Library Association : JMLA · 2026Article
- Estimating bias from withdrawal of life sustaining treatment in clinical trials.Critical care (London, England) · 2025Review
- High-dimensional analysis of injured patients reveals distinct circulating proteomic profiles in plasma vs. whole blood resuscitation.Cell reports. Medicine · 2025Article
- Haemostatic resuscitation in practice: a descriptive analysis of blood products administered during Operation HERRICK, Afghanistan.BMJ military health · 2025Article
- Selection bias in multidrug-resistant tuberculosis cohort studies assessing sputum culture conversion.PloS one · 2022Article
- Retrospective study on rib fractures: smoking and alcohol matter for mortality and complications.Trauma surgery & acute care open · 2021Article
- Observational
- Estimating the ratio of multivariate recurrent event rates with application to a blood transfusion study.Statistical methods in medical research · 2017Article
- Hypertonic Saline Primes Activation of the p53-p21 Signaling Axis in Human Small Airway Epithelial Cells That Prevents Inflammation Induced by Pro-inflammatory Cytokines.Journal of proteome research · 2016Article
- Recurrent event frailty models reduced time-varying and other biases in evaluating transfusion protocols for traumatic hemorrhage.Journal of clinical epidemiology · 2016Observational
- A joint latent class analysis for adjusting survival bias with application to a trauma transfusion study.Statistics in medicine · 2016Article
- Article
- Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries.Journal of extracellular vesicles · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCollider bias, or stratifying data by a covariate consequence rather than cause (confounder) of treatment and outcome, plagues randomised and observational trauma research. Of the seven trials of prehospital hypertonic saline in dextran (HSD) that have been evaluated in systematic reviews, none found an overall between-group difference in survival, but four reported significant subgroup effects. We hypothesised that an avoidable type of collider bias often introduced inadvertently into trauma comparative effectiveness research could explain the incongruous findings.
methodsThe two most recent HSD trials, a single-site pilot and a multi-site pivotal study, provided data for a secondary analysis to more closely examine the potential for collider bias. The two trials had followed the a priori statistical analysis plan to subgroup patients by a post-randomisation covariate and well-established surrogate for bleeding severity, massive transfusion (MT), ≥ 10 unit of red blood cells within 24h of admission. Despite favourable HSD effects in the MT subgroup, opposite effects in the non-transfused subgroup halted the pivotal trial early. In addition to analyzing the data from the two trials, we constructed causal diagrams and performed a meta-analysis of the results from all seven trials to assess the extent to which collider bias could explain null overall effects with subgroup heterogeneity.
resultsAs in previous trials, HSD induced significantly greater increases in systolic blood pressure (SBP) from prehospital to admission than control crystalloid (p=0.003). Proportionately more HSD than control decedents accrued in the non-transfused subgroup, but with paradoxically longer survival. Despite different study populations and a span of over 20 years across the seven trials, the reported mortality effects were consistently null, summary RR=0.99 (p=0.864, homogeneity p=0.709).
conclusionsHSD delayed blood transfusion by modifying standard triggers like SBP with no detectable effect on survival. The reported heterogeneous HSD effects in subgroups can be explained by collider bias that trauma researchers can avoid by improved covariate selection and data capture strategies.
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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.