Evidence map›Paper›PMID 41677175›Full record

ArticleStatistics in medicine2026

A Novel Method for Inserting Dose Levels Mid-Trial in Early-Phase Oncology Combination Studies.

Matthew George, Ian Wadsworth, Pavel Mozgunov

Abstract read
In one paragraph

Article in Statistics in medicine, 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

3 authors.

Matthew GeorgePhastar, London, UK.
Ian WadsworthPhastar, London, UK.
Pavel MozgunovMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.

Funding

National Institute for Health and Care Research NIHR300576UK Medical Research Council MC UU 00040/03
6 · The paper itself

Abstract

The use of combination treatments in early-phase oncology trials is growing. The objective of these trials is to search for the maximum tolerated dose combination from a predefined set. However, cases in which the initial set of combinations does not contain one close to the target toxicity pose a significant challenge. Currently, solutions are typically ad hoc and may bring practical challenges. We propose a novel method for inserting dose levels mid-trial, which features a search for the contour partitioning the dose space into combinations with toxicity truly above and below the target toxicity. Establishing this contour with a degree of certainty suggests that no combination is close to the target toxicity, triggering an insertion. We examine our approach in a comprehensive simulation study applied to the PIPE design and two-dimensional Bayesian logistic regression model (BLRM), though any model-based or model-assisted design is an appropriate candidate. Our results demonstrate that, on average, the insertion method can increase the probability of selecting combinations close to the target toxicity, without increasing the probability of subtherapeutic or toxic recommendations.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsMaximum Tolerated DoseNeoplasmsBayes TheoremComputer SimulationDose-Response Relationship, DrugHumansLogistic ModelsModels, Statisticaladaptive designscombination trialsdose‐findingdose insertions

Identifiers

PMID41677175
PMCPMC12917875

What OpenQuestion holds

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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.