ArticleJournal of the National Cancer Institute2023
Seamless phase II/III design: a useful strategy to reduce the sample size for dose optimization.
Article in Journal of the National Cancer Institute, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis 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
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Adaptive designs in clinical trials: a systematic review-part I.BMC medical research methodology · 2024Pooled it
- GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial.JAMA network open · 2024Trial
- From Phase Ib/II to Seamless Phase II/III: A Simulation-Based Discussion of Design Strategies for Dose Optimization and Confirmatory Phase.Clinical pharmacology and therapeutics · 2026Article
- Integrating a pilot study and large trial into one adaptive design.Contemporary clinical trials · 2025Article
- BARD: A seamless two-stage dose optimization design integrating backfill and adaptive randomization.Clinical trials (London, England) · 2025Article
- Adaptive phase I-II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies.Clinical trials (London, England) · 2024Review
- Statistical and practical considerations in planning and conduct of dose-optimization trials.Clinical trials (London, England) · 2024Review
- A generalized phase 1-2-3 design integrating dose optimization with confirmatory treatment comparison.Biometrics · 2024Article
- Hierarchical Composite Endpoints for Dose Optimization in Early Phase Oncology Trials.Pharmaceutical statisticsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe traditional more-is-better dose selection paradigm, originally developed for cytotoxic chemotherapeutics, can be problematic when applied to the development of novel molecularly targeted agents. Recognizing this issue, the US Food and Drug Administration initiated Project Optimus to reform the dose optimization and selection paradigm in oncology drug development, emphasizing the need for greater attention to benefit-risk considerations.
methodsWe identify different types of phase II/III dose-optimization designs, classified according to trial objectives and endpoint types. Through computer simulations, we examine their operating characteristics and discuss the relevant statistical and design considerations for effective dose optimization.
resultsPhase II/III dose-optimization designs are capable of controlling family-wise type I error rates and achieving appropriate statistical power with substantially smaller sample sizes than the conventional approach while also reducing the number of patients who experience toxicity. Depending on the design and scenario, the sample size savings range from 16.6% to 27.3%, with a mean savings of 22.1%.
conclusionsPhase II/III dose-optimization designs offer an efficient way to reduce sample sizes for dose optimization and accelerate the development of targeted agents. However, because of interim dose selection, the phase II/III dose-optimization design presents logistical and operational challenges and requires careful planning and implementation to ensure trial integrity.
Indexed as
Identifiers
What OpenQuestion holds
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.