Adaptive designs in clinical trials: a systematic review-part I.

Autor: Ben-Eltriki M; Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada. mbeneltriki@alumni.ubc.ca.; George and for Fay Yee Centre Healthcare Innovation, Winnipeg, MB, Canada. mbeneltriki@alumni.ubc.ca.; Cochrane Hypertension Review Group, Therapeutic Initiative, University of British Columbia, Vancouver, BC, Canada. mbeneltriki@alumni.ubc.ca., Rafiq A; Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada., Paul A; Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada., Prabhu D; George and for Fay Yee Centre Healthcare Innovation, Winnipeg, MB, Canada., Afolabi MOS; Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada., Baslhaw R; George and for Fay Yee Centre Healthcare Innovation, Winnipeg, MB, Canada.; Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada., Neilson CJ; Neil John Maclean Health Sciences Library, University of Manitoba, Winnipeg, MB, Canada., Driedger M; Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada., Mahmud SM; Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada., Lacaze-Masmonteil T; Department of Pediatrics, Cumming School of Medicine, University of Calgary, Alberta, Canada., Marlin S; Clinical Trials Ontario, Toronto, Ontario, Canada., Offringa M; Department of Paediatrics, Management & Evaluation, Institute of Health Policy, University of Toronto, Ontario, Canada.; The Hospital for Sick Children, Toronto, Ontario, Canada., Butcher N; The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada., Heath A; The Hospital for Sick Children, Toronto, Ontario, Canada.; Division of Biostatistics, Dalla Lana School of Public Health, Child Health Evaluative Sciences, University of Toronto, ScientistToronto, Ontario, Canada.; Department of Statistical Science, University College London, London, UK., Kelly LE; Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada. lauren.kelly@umanitoba.ca.; George and for Fay Yee Centre Healthcare Innovation, Winnipeg, MB, Canada. lauren.kelly@umanitoba.ca.; Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. lauren.kelly@umanitoba.ca.; Departments of Pharmacology and Therapeutics, Community Health Sciences, University of Manitoba, 417-753 McDermot Ave, Winnipeg, Manitoba, R3E0T6, Canada. lauren.kelly@umanitoba.ca.
Jazyk: angličtina
Zdroj: BMC medical research methodology [BMC Med Res Methodol] 2024 Oct 04; Vol. 24 (1), pp. 229. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1186/s12874-024-02272-9
Abstrakt: Background: Adaptive designs (ADs) are intended to make clinical trials more flexible, offering efficiency and potentially cost-saving benefits. Despite a large number of statistical methods in the literature on different adaptations to trials, the characteristics, advantages and limitations of such designs remain unfamiliar to large parts of the clinical and research community. This systematic review provides an overview of the use of ADs in published clinical trials (Part I). A follow-up (Part II) will compare the application of AD in trials in adult and pediatric studies, to provide real-world examples and recommendations for the child health community.
Methods: Published studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical Abstracts (Ovid). Clinical trial protocols, reports, and a secondary analyses using AD were included. We excluded trial registrations and interventions other than drugs or vaccines to align with regulatory guidance. Data from the published literature on study characteristics, types of adaptations, statistical analysis, stopping boundaries, logistical challenges, operational considerations and ethical considerations were extracted and summarized herein.
Results: Out of 23,886 retrieved studies, 317 publications of adaptive trials, 267 (84.2%) trial reports, and 50 (15.8%) study protocols), were included. The most frequent disease was oncology (168/317, 53%). Most trials included only adult participants (265, 83.9%),16 trials (5.4%) were limited to only children and 28 (8.9%) were for both children and adults, 8 trials did not report the ages of the included populations. Some studies reported using more than one adaptation (there were 390 reported adaptations in 317 clinical trial reports). Most trials were early in drug development (phase I, II (276/317, 87%). Dose-finding designs were used in the highest proportion of the included trials (121/317, 38.2 %). Adaptive randomization (53/317, 16.7%), with drop-the-losers (or pick-the-winner) designs specifically reported in 29 trials (9.1%) and seamless phase 2-3 design was reported in 27 trials (8.5%). Continual reassessment methods (60/317, 18.9%) and group sequential design (47/317, 14.8%) were also reported. Approximately two-thirds of trials used frequentist statistical methods (203/309, 64%), while Bayesian methods were reported in 24% (75/309) of included trials.
Conclusion: This review provides a comprehensive report of methodological features in adaptive clinical trials reported between 2010 and 2020. Adaptation details were not uniformly reported, creating limitations in interpretation and generalizability. Nevertheless, implementation of existing reporting guidelines on ADs and the development of novel educational strategies that address the scientific, operational challenges and ethical considerations can help in the clinical trial community to decide on when and how to implement ADs in clinical trials. STUDY PROTOCOL REGISTRATION: https://doi.org/10.1186/s13063-018-2934-7 .
(© 2024. The Author(s).)
Databáze: MEDLINE
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