SynthesisBMJ open2021
Testing for non-inferior mortality: a systematic review of non-inferiority margin sizes and trial characteristics.
Synthesis in BMJ open, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis 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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Seven vs Fourteen Days of Antibiotics for Gram-Negative Bloodstream Infection: A Systematic Review and Noninferiority Meta-Analysis.JAMA network open · 2025Pooled it
- Efficacy and safety of nalbuphine vs. pethidine in oocyte retrieval: a non-inferiority, double-blinded, randomized controlled trial.Frontiers in reproductive health · 2026Trial
- Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial.BMJ (Clinical research ed.) · 2023Trial
- Trial
- Trial
- Reduced-volume radiotherapy versus conventional-volume radiotherapy after induction chemotherapy in nasopharyngeal carcinoma: An open-label, noninferiority, multicenter, randomized phase 3 trial.CA: a cancer journal for cliniciansTrial
- Defining a Non-Inferiority Margin for Delirium Resolution in a Clinical Trial of Older Adults With Bacteriuria and Abnormal Urine Tests.Journal of the American Geriatrics Society · 2026Article
- Efficacy and safety of RApid PrednIsolone Dose reduction for acute exacerbation of Idiopathic Pulmonary Fibrosis (RAPID-IPF Trial): a study protocol for a randomised controlled trial.BMJ open respiratory research · 2026Article
- Article
- ADJUVANT Randomized Controlled Trial: Rationale and Design.Journal of the American Heart Association · 2026Article
- Clinical and methodological considerations from the RENOVATE trial.Journal of thoracic disease · 2026Article
- Clinical equivalence and non-inferiority within health technology assessment.The European journal of health economics : HEPAC : health economics in prevention and care · 2026Article
- Recommended methodologies for clinical investigations of high-risk medical devices-Conclusions from the European Union CORE-MD Project.The Lancet regional health. Europe · 2025Review
- Article
- Article
- The impact of a medically directed student registered nurse anesthesia staffing model on Postprocedural patient outcomes.Journal of clinical anesthesia · 2024Article
- Cardiovascular Safety of Testosterone-Replacement Therapy: Critical Appraisal of a Currently Published Clinical Trial.Arquivos brasileiros de cardiologia · 2024Article
- Short-course antibiotic therapy of 5 days in community-acquired pneumonia (CAP5): study protocol for a randomised controlled trial.BMJ open · 2023Article
- Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2023Article
- Noninferiority Margin Size and Acceptance of Trial Results: Contingent Valuation Survey of Clinician Preferences for Noninferior Mortality.Medical decision making : an international journal of the Society for Medical Decision Making · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo describe the size and variability of non-inferiority margins used in non-inferiority trials of medications with primary outcomes involving mortality, and to examine the association between trial characteristics and non-inferiority margin size.
designSystematic review. DATA SOURCES: Medline, Medline In Process, Medline Epub Ahead of Print and Embase Classic+Embase databases from January 1989 to December 2019. ELIGIBILITY CRITERIA: Prospective non-inferiority randomised controlled trials comparing pharmacological therapies, with primary analyses for non-inferiority and primary outcomes involving mortality alone or as part of a composite outcome. Trials had to prespecify non-inferiority margins as absolute risk differences or relative to risks of outcome and provide a baseline risk of primary outcome in the control intervention.
results3992 records were screened, 195 articles were selected for full text review and 111 articles were included for analyses. 82% of trials were conducted in thrombosis, infectious diseases or oncology. Mortality was the sole primary outcome in 23 (21%) trials, and part of a composite primary outcome in 88 (79%) trials. The overall median non-inferiority margin was an absolute risk difference of 9% (IQR 4.2%-10%). When non-inferiority margins were expressed relative to the baseline risk of primary outcome in control groups, the median relative non-inferiority margin was 1.5 (IQR 1.3-1.7). In multivariable regression analyses examining the association between trial characteristics (medical specialty, inclusion of paediatric patients, mortality as a sole or part of a composite primary outcome, presence of industry funding) and non-inferiority margin size, only medical specialty was significantly associated with non-inferiority margin size.
conclusionAbsolute and relative non-inferiority margins used in published trials comparing medications are large, allowing conclusions of non-inferiority in the context of large differences in mortality. Accepting the potential for large increases in outcomes involving mortality while declaring non-inferiority is a challenging methodological issue in the conduct of non-inferiority trials.
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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.