Adaptive designs in clinical trials: a systematic review-part I
Notice bibliographique
Résumé
Abstract Background: Adaptive designs (ADs) are intended to make clinical trials more flexible, offering efficient and potentially cost-saving benefits. Despite a large number of methods-based research papers in the literature on different adaptations to trials, the advantages and limitations of such designs remain unfamiliar to large parts of the clinical community including those in pediatric medicine where efficient clinical trials are essential to inform care. This systematic review provides an overview of the use of ADs in published clinical trials (Part I) and compares the application of AD in trials in adult and pediatric studies, providing real-world examples and recommendations for the child health community (Part II). Methods: Published studies from 2010 to April 2020 were searched in the following databases: MEDLINE (Ovid), Embase (Ovid), and International Pharmaceutical Abstracts (Ovid). Protocols, reports, and a secondary analysis using AD were included. We did not include any trial registrations and interventions other than drugs or vaccines. 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. 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. Dose finding designs were used in the highest proportion of the included AD (82, 22.4 %), followed by adaptive randomization (56, 14.4%), group sequential design in 47 trials (12.8%), then drop-the-losers (pick-the-winner) design in 28 trials (7.6%) and seamless phase 2-3 design in 27 trials (7.4%). Approximately 203 (64%) studies used frequentist statistical methods and 75 (23.7%) used Bayesian methods. Conclusion: In Part I of this review, we provide a comprehensive overview of the landscape and methodological features of adaptive clinical trials. We found that adaptive designs were applied mostly in Phase II oncology trials, aimed to establish efficacy and determine the choice of doses for the Phase III of the trials. Phase I trials of new drugs that included adaptations most frequently aimed to identify the maximum tolerable dose. Adaptation details were not uniformly reported across all trials and were hardly reported in the pediatric trials. Study protocol registration: DOI:10.1186/s13063-018-2934-7
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,462 | 0,932 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,010 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,002 | 0,004 |
| Intégrité de la recherche | 0,002 | 0,012 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; les deux têtes enseignantes s’accordent sur ce qui est montré ici.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».