Evidence map›Paper›PMID 27855102›Full record

SynthesisBMJ open2016

Non-inferiority trials: are they inferior? A systematic review of reporting in major medical journals.

Sunita Rehal, Tim P Morris, Katherine Fielding, James R Carpenter, Patrick P J Phillips

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMJ open, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 7 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.

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

71 citing papers in PubMed, 7 syntheses or guidelines pooled it.

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11 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

5 authors.

Sunita RehalMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK.ORCID 0000-0002-2578-5778
Tim P MorrisMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK.
Katherine FieldingMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK.
James R CarpenterMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK.
Patrick P J PhillipsMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK.

Funding

Medical Research Council 1546500Medical Research Council 510636Medical Research Council 532196Medical Research Council MC_UU_12023/21Medical Research Council MC_UU_12023/27
6 · The paper itself

Abstract

objectiveTo assess the adequacy of reporting of non-inferiority trials alongside the consistency and utility of current recommended analyses and guidelines.

designReview of randomised clinical trials that used a non-inferiority design published between January 2010 and May 2015 in medical journals that had an impact factor >10 (JAMA Internal Medicine, Archives Internal Medicine, PLOS Medicine, Annals of Internal Medicine, BMJ, JAMA, Lancet and New England Journal of Medicine). DATA SOURCES: Ovid (MEDLINE).

methodsWe searched for non-inferiority trials and assessed the following: choice of non-inferiority margin and justification of margin; power and significance level for sample size; patient population used and how this was defined; any missing data methods used and assumptions declared and any sensitivity analyses used.

resultsA total of 168 trial publications were included. Most trials concluded non-inferiority (132; 79%). The non-inferiority margin was reported for 98% (164), but less than half reported any justification for the margin (77; 46%). While most chose two different analyses (91; 54%) the most common being intention-to-treat (ITT) or modified ITT and per-protocol, a large number of articles only chose to conduct and report one analysis (65; 39%), most commonly the ITT analysis. There was lack of clarity or inconsistency between the type I error rate and corresponding CIs for 73 (43%) articles. Missing data were rarely considered with (99; 59%) not declaring whether imputation techniques were used.

conclusionsReporting and conduct of non-inferiority trials is inconsistent and does not follow the recommendations in available statistical guidelines, which are not wholly consistent themselves. Authors should clearly describe the methods used and provide clear descriptions of and justifications for their design and primary analysis. Failure to do this risks misleading conclusions being drawn, with consequent effects on clinical practice.

Indexed as

PublishingResearch DesignBiasBiomedical ResearchGuidelines as TopicHumansJournal Impact FactorPatient SelectionPeriodicals as TopicSample SizeStatistics as Topicclinical trialnon-inferiorityrandomised controlled clinical trialssystematic review

Identifiers

PMID27855102
PMCPMC5073571

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.