Evidence map›Paper›PMID 40854849›Full record

ArticleBMJ open2025

Disparity between statistical significance and clinical importance in published randomised controlled trials: a methodological study.

Tonya Marianne Esterhuizen, Lawrence Mbuagbaw, Nadia Rehman, Nathan Yanwou, Devron J Swaby, Esme Kittle, Johann-Christoph Licht, Lehana Thabane

Abstract read
In one paragraph

Article in BMJ open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Reporting of second-generationContemporary clinical trials communications · 2026
    Article
  3. Article
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

8 authors.

Tonya Marianne EsterhuizenDivision of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa tonyae@sun.ac.za.ORCID http://orcid.org/0000-0002-8703-1664
Lawrence MbuagbawDivision of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa.ORCID http://orcid.org/0000-0001-5855-5461
Nadia RehmanDepartment of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.ORCID http://orcid.org/0000-0002-0174-1527
Nathan YanwouPublic Health and Preventive Medicine Residency Program, McGill University, Montreal, Québec, Canada.
Devron J SwabySchool of Interdisciplinary Science, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Esme KittleSchool of Medicine, University of Limerick, Limerick, Ireland.
Johann-Christoph LichtSchool of Medicine, University of Limerick, Limerick, Ireland.
Lehana ThabaneDivision of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape, South Africa.ORCID http://orcid.org/0000-0003-0355-9734

Funding

African Centre for Biostatistical ExcellenceD43TW010547 · FIC · STELLENBOSCH UNIVERSITY · PI Rhoderick Machekano, Taryn Natalie Young · 2017 to 2026
$3.1M
FIC NIH HHS D43 TW010547
6 · The paper itself

Abstract

objectivesWe estimated the extent of the disparity between statistical significance and clinical importance in published randomised controlled trials (RCTs), and explored factors associated with this disparity.

designA methodological study of trials published between 2018 and 2022 and indexed in PubMed was conducted. Primary reports of two-arm, phase three, superiority trials of human health interventions were included. Pharmacokinetic studies and pilot trials were excluded. The relationship between the specified delta value or minimum clinically important difference (as specified in the sample size calculation) and the effect size determined the clinical importance of the trial results. Studies where the clinical importance was at least possible, with no statistical significance, were classified as SS-CI+ disparity, and studies which were definitely not clinically important but statistically significant were classified as SS+CI- disparity. Factors associated with each type of disparity were explored at the study level using multinomial logistic regression.

results500 trials were included. In 38.4% (n=192) of these, information was not available to classify clinical importance. Overall disparity was found in 63 of the remaining 308 studies, 20.5% (95% confidence interval (CI) 16.2% to 25.5%). SS+CI- disparity was 10.3% (15/145) (95% CI 6.1% to 16.8%) and SS-CI+ disparity was 29.5% (48/163) (95% CI 22.7% to 37.2%).Studies testing complementary or alternative medicines relative to drug trials were positively associated with SS+CI- disparity. Low journal impact factor, small sample size, unfunded or grant funding and failure to mention allocation concealment were positively associated with SS-CI+disparity.

conclusionsIn up to 20% of RCTs, there may be a disparity between statistical significance and clinical importance. Clinical importance of results should be taken into account in the interpretation of trial results, and trials should adhere stringently to reporting guidelines.

Indexed as

Randomized Controlled Trials as TopicResearch DesignClinical RelevanceData Interpretation, StatisticalHumansSample SizeClinical RelevanceRandomized Controlled TrialResearch DesignSTATISTICS & RESEARCH METHODS

Identifiers

PMID40854849
PMCPMC12414192

What Socratic holds

Textmetadata
LicenceCC BY-NC
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Registered trials

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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 Socratic graph.