Evidence map›Paper›PMID 41626892›Full record

ArticleResearch synthesis methods2026

Estimands and their implications for evidence synthesis for oncology: A simulation study of treatment switching in meta-analysis.

Rebecca Kathleen Metcalfe, Antonio Remiro-Azócar, Quang Vuong, Anders Gorst-Rasmussen, Oliver Keene, Shomoita Alam, Jay J H Park

Abstract read
In one paragraph

Article in Research synthesis methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

7 authors.

Rebecca Kathleen MetcalfeCore Clinical Sciences, Inc., Vancouver, BC, Canada.
Antonio Remiro-AzócarMethods and Outreach, Novo Nordisk Pharma, Madrid, Spain.ORCID https://orcid.org/0000-0002-2877-2315
Quang VuongCore Clinical Sciences, Inc., Vancouver, BC, Canada.
Anders Gorst-RasmussenBiostatistics HTA, https://ror.org/0435rc536Novo Nordisk A/S, Søborg, Denmark.
Oliver KeeneKeeneONStatistics, Maidenhead, UK.
Shomoita AlamCore Clinical Sciences, Inc., Vancouver, BC, Canada.
Jay J H ParkCore Clinical Sciences, Inc., Vancouver, BC, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ICH E9(R1) addendum provides guidelines on accounting for intercurrent events in clinical trials using the estimands framework. However, there has been limited attention to the estimands framework for meta-analysis. Using treatment switching, a well-known intercurrent event that occurs frequently in oncology, we conducted a simulation study to explore the bias introduced by pooling together estimates targeting different estimands in a meta-analysis of randomized clinical trials (RCTs) that allowed treatment switching. We simulated overall survival data of a collection of RCTs that allowed patients in the control group to switch to the intervention treatment after disease progression under fixed effects and random effects models. For each RCT, we calculated effect estimates for a treatment policy estimand that ignored treatment switching, and a hypothetical estimand that accounted for treatment switching either by fitting rank-preserving structural failure time models or by censoring switchers. Then, we performed random effects and fixed effects meta-analyses to pool together RCT effect estimates while varying the proportions of trials providing treatment policy and hypothetical effect estimates. We compared the results of meta-analyses that pooled different types of effect estimates with those that pooled only treatment policy or hypothetical estimates. We found that pooling estimates targeting different estimands results in pooled estimators that do not target any estimand of interest, and that pooling estimates of varying estimands can generate misleading results, even under a random effects model. Adopting the estimands framework for meta-analysis may improve alignment between meta-analytic results and the clinical research question of interest.

Indexed as

Medical OncologyMeta-Analysis as TopicNeoplasmsAlgorithmsBiasComputer SimulationData Interpretation, StatisticalHumansModels, StatisticalRandomized Controlled Trials as TopicResearch Designestimandsevidence synthesisICH E9(R1)meta-analysisoncologytreatment switching

Identifiers

PMID41626892
PMCPMC12824772

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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 OpenQuestion graph.