ArticleStatistical methods in medical research2022
Challenges of modelling approaches for network meta-analysis of time-to-event outcomes in the presence of non-proportional hazards to aid decision making: Application to a melanoma network.
Article in Statistical methods in medical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 5 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
12 citing papers in PubMed, 5 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Pooled it
- Treatments for renal cell carcinoma: NICE Pilot Treatment Pathways Appraisal.Health technology assessment (Winchester, England) · 2026Pooled it
- Lenvatinib plus pembrolizumab for untreated advanced renal cell carcinoma: a systematic review and cost-effectiveness analysis.Health technology assessment (Winchester, England) · 2024Pooled it
- Pooled it
- A systematic review and network meta-analysis of first-line immune checkpoint inhibitor combination therapies in patients with advanced non-squamous non-small cell lung cancer.Frontiers in immunology · 2022Pooled it
- Unanchored simulated treatment comparison on survival outcomes using parametric and Royston-Parmar models with application to lenvatinib plus pembrolizumab in renal cell carcinoma.BMC medical research methodology · 2025Trial
- Evidence Synthesis via Indirect Treatment Comparisons in the European Framework of Joint Clinical Assessment.Epidemiologia (Basel, Switzerland) · 2026Review
- NMAsurv: An R Shiny application for network meta-analysis based on survival data.Research synthesis methods · 2025Review
- One-step parametric network meta-analysis models using the exact likelihood that allow for time-varying treatment effects.Research synthesis methods · 2025Article
- Survival analysis of Kasturi tobacco plants in Jember district using the stratified cox and extended cox models.MethodsX · 2025Article
- Article
- Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma.Journal of comparative effectiveness research · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSynthesis of clinical effectiveness from multiple trials is a well-established component of decision-making. Time-to-event outcomes are often synthesised using the Cox proportional hazards model assuming a constant hazard ratio over time. However, with an increasing proportion of trials reporting treatment effects where hazard ratios vary over time and with differing lengths of follow-up across trials, alternative synthesis methods are needed.
objectivesTo compare and contrast five modelling approaches for synthesis of time-to-event outcomes and provide guidance on key considerations for choosing between the modelling approaches.
methodsThe Cox proportional hazards model and five other methods of estimating treatment effects from time-to-event outcomes, which relax the proportional hazards assumption, were applied to a network of melanoma trials reporting overall survival: restricted mean survival time, generalised gamma, piecewise exponential, fractional polynomial and Royston-Parmar models.
resultsAll models fitted the melanoma network acceptably well. However, there were important differences in extrapolations of the survival curve and interpretability of the modelling constraints demonstrating the potential for different conclusions from different modelling approaches.
conclusionThe restricted mean survival time, generalised gamma, piecewise exponential, fractional polynomial and Royston-Parmar models can accommodate non-proportional hazards and differing lengths of trial follow-up within a network meta-analysis of time-to-event outcomes. We recommend that model choice is informed using available and relevant prior knowledge, model transparency, graphically comparing survival curves alongside observed data to aid consideration of the reliability of the survival estimates, and consideration of how the treatment effect estimates can be incorporated within a decision model.
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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.