ArticleAnnals of internal medicine2015
Alternatives to Hazard Ratios for Comparing the Efficacy or Safety of Therapies in Noninferiority Studies.
Article in Annals of internal medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 3 of them syntheses 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
96 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Beyond hazard ratios: appropriate statistical methods for quantifying the clinical effectiveness of immune-oncology therapies - the example of the Netherlands.BMC medical research methodology · 2024Pooled it
- Immunotherapy in advanced kidney cancer: an alternative meta-analytic method using reconstructed survival data in case of proportional hazard assumption violation.Frontiers in oncology · 2022Pooled it
- Correlation of Milestone Restricted Mean Survival Time Ratio With Overall Survival Hazard Ratio in Randomized Clinical Trials of Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.JAMA network open · 2019Pooled it
- Exploratory Time-Dependent Patterns in Estimated Treatment Effect of Talazoparib Plus Enzalutamide in HRR Non-Deficient or Unknown Metastatic Castration-Resistant Prostate Cancer: A Post Hoc Analysis of the TALAPRO-2 Trial.International journal of urology : official journal of the Japanese Urological Association · 2026Trial
- Trial
- Survival outcomes of population-wide colonoscopy screening: reanalysis of the NordICC data.BMC gastroenterology · 2024Trial
- A comparison of different population-level summary measures for randomised trials with time-to-event outcomes, with a focus on non-inferiority trials.Clinical trials (London, England) · 2023Trial
- Restricted mean survival time versus conventional effect summary for treatment decision-making: A mixed-methods study.Journal of the American Geriatrics Society · 2023Trial
- Trial
- Pravastatin for Primary Prevention in Older Adults: Restricted Mean Survival Time Analysis.Journal of the American Geriatrics Society · 2018Trial
- Robot-Assisted Minimally Invasive Direct Coronary Artery Bypass Graft in High-Risk Patients with Reduced Left Ventricular Function: Comparison with Conventional Off-Pump Coronary Artery Bypass Graft Surgery.Medicina (Kaunas, Lithuania) · 2026Article
- Design and Analysis of Randomized Clinical Trials With Average Hazard: Practical Guidance and Tools for Implementation.Statistics in medicine · 2026Article
- Patient-Centric Pragmatic Clinical Trials: Opening the DOOR.Statistics in medicine · 2026Article
- Determining the threshold time in restricted mean survival time analysis for two group comparisons with applications in clinical and epidemiology studies.American journal of epidemiology · 2026Article
- Comparative effectiveness research with average hazard for censored time-to-event outcomes: simulation study and application to observational data.BMC medical research methodology · 2025Article
- Ensuring Quality and Interpretability of Progression Free Survival and Overall Survival in Oncology Clinical Trials.Therapeutic innovation & regulatory science · 2025Article
- Assessing delayed treatment benefits of immunotherapy using long-term average hazard: a novel test/estimation approach.Lifetime data analysis · 2025Article
- Power and sample size calculation for non-inferiority trials with treatment switching in intention-to-treat analysis comparing RMSTs.BMC medical research methodology · 2025Article
- Prognostic significance of right ventricular dysfunction in heart failure with preserved ejection fraction: a meta-analysis of reconstructed time-to-event data.Echo research and practice · 2025Article
- Summary measures in non-inferiority clinical trials with a time-to-event outcome: an empirical comparison of power.BMC medical research methodology · 2025Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
A noninferiority study is often used to investigate whether a treatment's efficacy or safety profile is acceptable compared with an alternative therapy regarding the time to a clinical event. The empirical quantification of the treatment difference for such a study is routinely based on the hazard ratio (HR) estimate. The HR, which is not a relative risk, may be difficult to interpret clinically, especially when the underlying proportional hazards assumption is violated. The precision of the HR estimate depends primarily on the number of observed events but not directly on exposure times or sample size of the study population. If the event rate is low, the study may require an impractically large number of events to ensure that the prespecified noninferiority criterion for the HR is attainable. This article discusses deficiencies in the current approach for the design and analysis of a noninferiority study. Alternative procedures are provided, which do not depend on any model assumption, to compare 2 treatments. For a noninferiority safety study, the patients' exposure times are more clinically important than the observed number of events. If the patients' exposure times are long enough to evaluate safety reliably, then these alternative procedures can effectively provide clinically interpretable evidence on safety, even with relatively few observed events. These procedures are illustrated with data from 2 studies. One explores the cardiovascular safety of a pain medicine; the second examines the cardiovascular safety of a new treatment for diabetes. These alternative strategies to evaluate safety or efficacy of an intervention lead to more meaningful interpretations of the analysis results than the conventional strategy that uses the HR estimate.
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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.