ArticleBiometrical journal. Biometrische Zeitschrift2025
Estimands for Early-Phase Dose Optimization Trials in Oncology.
Article in Biometrical journal. Biometrische Zeitschrift, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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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
2 citing papers in PubMed.
- PRO-ADD: Patient-empowered dose-finding trials integrating safety, preliminary efficacy and patient-reported outcomes for optimal dose selection.Statistical methods in medical research · 2026Article
- Estimands for Early-Phase Dose Optimization Trials in Oncology.Biometrical journal. Biometrische Zeitschrift · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose. However, with the advent of molecular-targeted therapies and antibody drug conjugates, dose-limiting toxicities are less frequently observed, giving rise to the concept of optimal biological dose (OBD), which considers both efficacy and toxicity. The estimand framework presented in the addendum of the ICH E9(R1) guidelines strengthens the dialogue between different stakeholders by bringing in greater clarity in the clinical trial objectives and by providing alignment between the targeted estimand under consideration and the statistical analysis methods. However, there is a lack of clarity in implementing this framework in early-phase dose optimization studies. This paper aims to discuss the estimand framework for dose optimization trials in oncology, considering efficacy and toxicity through utility functions. Such trials should include pharmacokinetics data, toxicity data, and efficacy data. Based on these data, the analysis methods used to identify the optimized dose/s are also described. Focusing on optimizing the utility function to estimate the OBD, the population-level summary measure should reflect only the properties used for estimating this utility function. A detailed strategy recommendation for intercurrent events has been provided using a real-life oncology case study. Key recommendations regarding the estimand attributes include that in a seamless phase I/II dose optimization trial, the treatment attribute should start when the subject receives the first dose. We argue that such a framework brings in additional clarity to dose optimization trial objectives and strengthens the understanding of the drug under consideration, which would enable the correct dose to move to phase II of clinical development.
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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.