ArticlePharmaceutical research2015
Influence of the Size of Cohorts in Adaptive Design for Nonlinear Mixed Effects Models: An Evaluation by Simulation for a Pharmacokinetic and Pharmacodynamic Model for a Biomarker in Oncology.
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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
6 citing papers in PubMed.
- Advances and Further Comparison of Software Tools for Fisher Information Matrix-Based Design Evaluation in Pharmacometrics.Pharmaceutical research · 2026Article
- Published population pharmacokinetic models of mycophenolate sodium: a systematic review and external evaluation in a Chinese sample of renal transplant recipients.Frontiers in pharmacology · 2025Article
- Lessons learned from IDeAl - 33 recommendations from the IDeAl-net about design and analysis of small population clinical trials.Orphanet journal of rare diseases · 2018Review
- Dose-finding methods for Phase I clinical trials using pharmacokinetics in small populations.Biometrical journal. Biometrische Zeitschrift · 2017Article
- Optimal Design for Informative Protocols in Xenograft Tumor Growth Inhibition Experiments in Mice.The AAPS journal · 2016Article
- Accelerating Monte Carlo power studies through parametric power estimation.Journal of pharmacokinetics and pharmacodynamics · 2016Article
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
purposeIn this study we aimed to evaluate adaptive designs (ADs) by clinical trial simulation for a pharmacokinetic-pharmacodynamic model in oncology and to compare them with one-stage designs, i.e., when no adaptation is performed, using wrong prior parameters.
methodsWe evaluated two one-stage designs, ξ0 and ξ*, optimised for prior and true population parameters, Ψ0 and Ψ*, and several ADs (two-, three- and five-stage). All designs had 50 patients. For ADs, the first cohort design was ξ0. The next cohort design was optimised using prior information updated from the previous cohort. Optimal design was based on the determinant of the Fisher information matrix using PFIM. Design evaluation was performed by clinical trial simulations using data simulated from Ψ*.
resultsEstimation results of two-stage ADs and ξ * were close and much better than those obtained with ξ 0. The balanced two-stage AD performed better than two-stage ADs with different cohort sizes. Three- and five-stage ADs were better than two-stage with small first cohort, but not better than the balanced two-stage design.
conclusionsTwo-stage ADs are useful when prior parameters are unreliable. In case of small first cohort, more adaptations are needed but these designs are complex to implement.
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.