ArticleJournal of the National Cancer Institute2023
Dose optimization during drug development: whether and when to optimize.
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 21 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Skipping a pillar does not make for strong foundations: Pharmacokinetic-pharmacodynamic reasoning behind the shape of dose-response relationships in oncology.CPT: pharmacometrics & systems pharmacology · 2023Pooled it
- High-throughput identification of bacterial β-glucuronidase inhibitors using machine learning.Gut microbes · 2026Article
- 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
- From authorisation to clinical practice: evolution of the use of biological medicines according to the SmPC and guidelines (2006 to 2025).European journal of clinical pharmacology · 2026Article
- Information borrowing in phase II randomized dose-ranging clinical trials in oncology.BMC medical research methodology · 2026Article
- Cinobufagin as a Potential Intervention Against Liver Cancer-A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Article
- Exposure-safety Markov modeling of ocular adverse events in patient populations treated with tisotumab vedotin.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Impact of Dose-Escalation Design on the Safety and Development of Anticancer Drugs in Clinical Trials.Clinical and translational science · 2025Article
- Bioactive compounds from marine algae in pancreatic cancer therapy: mechanistic insights into fucoidan and phlorotannins: a review.Medical oncology (Northwood, London, England) · 2025Review
- Totality of the Evidence: Optimizing Dosage Selection Strategies in Oncology.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Research Methods for "Dose-Effect-Toxicity" Relationship of Chinese Medicine Herbs.Chinese journal of integrative medicine · 2025Review
- Oncology Dose Optimization: Tailored Approaches to Different Molecular Classes.Clinical pharmacology and therapeutics · 2025Review
- Transforming Niclosamide through Nanotechnology: A Promising Approach for Long COVID Management.Small (Weinheim an der Bergstrasse, Germany) · 2025Review
- Posterior Predictive Design for Phase I Clinical Trials.Journal of the American Statistical Association · 2025Article
- Repurposing propofol for breast cancer therapy through promoting apoptosis and arresting cell cycle.Oncology reports · 2024Article
- Statistical and practical considerations in planning and conduct of dose-optimization trials.Clinical trials (London, England) · 2024Review
- Backfilling Patients in Phase I Dose-Escalation Trials Using Bayesian Optimal Interval Design (BOIN).Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Novel Clinical Trial Designs with Dose Optimization to Improve Long-term Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
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3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The goal of dose optimization during drug development is to identify a dose that preserves clinical benefit with optimal tolerability. Traditionally, the maximum tolerated dose in a small phase I dose escalation study is used in the phase II trial assessing clinical activity of the agent. Although it is possible that this dose level could be altered in the phase II trial if an unexpected level of toxicity is seen, no formal dose optimization has routinely been incorporated into later stages of drug development. Recently it has been suggested that formal dose optimization (involving randomly assigning patients between 2 or more dose levels) be routinely performed early in drug development, even before it is known that the experimental therapy has any clinical activity at any dose level. We consider the relative merits of performing dose optimization earlier vs later in the drug development process and demonstrate that a considerable number of patients may be exposed to ineffective therapies unless dose optimization is delayed until after clinical activity or benefit of the new agent has been established. We conclude that patient and public health interests may be better served by conducting dose optimization after (or during) phase III evaluation, with some exceptions when dose optimization should be performed after activity shown in phase II evaluation.
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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.