Evidence map›Paper›PMID 24755011›Full record

ArticleTrials2014

The risks and rewards of covariate adjustment in randomized trials: an assessment of 12 outcomes from 8 studies.

Brennan C Kahan, Vipul Jairath, Caroline J Doré, Tim P Morris

3 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 243 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
243citing papers in PubMed, 9 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

NCT05457972 phase4recruitingnot on this mapstarted 2025, after this paper: background citation

Postpartum Vaginal Estrogen for Sexual Function in Breastfeeding Patients: A Randomized Controlled Trial

TypeinterventionalSponsorUniversity Hospitals Cleveland Medical CenterRan2025 to 2026Enrolled100ConditionsBreastfeeding, Postpartum Sexual Dysfunction, Vaginal AtrophyArmsEstradiol, Vaginal Moisturizer
NCT07002294 narecruitingnot on this mapstarted 2026, after this paper: background citation

The Effect of SPecialty cAre on Recovery From Cardiac Arrest Trial (the SPARC Trial)

TypeinterventionalSponsorUniversity of PittsburghRan2026 to 2032Enrolled1,618ConditionsCardiac Arrest (CA), Heart Arrest, Heart Arrest, Out-Of-HospitalArmsTransfer to specialty care, Usual care
NCT07512401 completednot on this map

Safety of Reduced Methotrexate Lab Monitoring: a Population-based, Target Trial Emulation Study

TypeobservationalSponsorMayo ClinicRan2012 to 2025Enrolled2,414ConditionsRheumatic DiseasesArmsStandard methotrexate lab monitoring, Reduced methotrexate lab monitoring
3 · Its place in the literature

Who cites it

243 citing papers in PubMed, 9 syntheses or guidelines pooled it.

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  5. Measuring quality of life in trials including patients on haemodialysis: methodological issues surrounding the use of the Kidney Disease Quality of Life Questionnaire.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022
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  6. Individual participant data meta-analysis versus aggregate data meta-analysis: A case study in eczema and food allergy prevention.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2022
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  16. Early exclusive enteral feeding in 30-33 weeks gestation infants: a randomized controlled trial.Journal of perinatology : official journal of the California Perinatal Association · 2025
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183 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Brennan C KahanPragmatic Clinical Trials Unit, Queen Mary University of London, London E1 2AB, UK. b.kahan@qmul.ac.uk.
Vipul Jairath
Caroline J Doré
Tim P Morris

Funding

Medical Research Council MC_EX_G0800814Medical Research Council MC_U122870183
6 · The paper itself

Abstract

backgroundAdjustment for prognostic covariates can lead to increased power in the analysis of randomized trials. However, adjusted analyses are not often performed in practice.

methodsWe used simulation to examine the impact of covariate adjustment on 12 outcomes from 8 studies across a range of therapeutic areas. We assessed (1) how large an increase in power can be expected in practice; and (2) the impact of adjustment for covariates that are not prognostic.

resultsAdjustment for known prognostic covariates led to large increases in power for most outcomes. When power was set to 80% based on an unadjusted analysis, covariate adjustment led to a median increase in power to 92.6% across the 12 outcomes (range 80.6 to 99.4%). Power was increased to over 85% for 8 of 12 outcomes, and to over 95% for 5 of 12 outcomes. Conversely, the largest decrease in power from adjustment for covariates that were not prognostic was from 80% to 78.5%.

conclusionsAdjustment for known prognostic covariates can lead to substantial increases in power, and should be routinely incorporated into the analysis of randomized trials. The potential benefits of adjusting for a small number of possibly prognostic covariates in trials with moderate or large sample sizes far outweigh the risks of doing so, and so should also be considered.

Indexed as

Data Interpretation, StatisticalModels, StatisticalAnalysis of VarianceComputer SimulationHumansLinear ModelsLogistic ModelsProportional Hazards ModelsRandomized Controlled Trials as TopicReproducibility of ResultsResearch Design

Identifiers

PMID24755011
PMCPMC4022337

What OpenQuestion holds

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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.