Sample size recalculation in three-stage clinical trials and its evaluation.
Adaptive trial design
Clinical trials
Performance evaluation
Sample size adaptation
Journal
BMC medical research methodology
ISSN: 1471-2288
Titre abrégé: BMC Med Res Methodol
Pays: England
ID NLM: 100968545
Informations de publication
Date de publication:
25 Sep 2024
25 Sep 2024
Historique:
received:
01
02
2024
accepted:
10
09
2024
medline:
26
9
2024
pubmed:
26
9
2024
entrez:
25
9
2024
Statut:
epublish
Résumé
In clinical trials, the determination of an adequate sample size is a challenging task, mainly due to the uncertainty about the value of the effect size and nuisance parameters. One method to deal with this uncertainty is a sample size recalculation. Thereby, an interim analysis is performed based on which the sample size for the remaining trial is adapted. With few exceptions, previous literature has only examined the potential of recalculation in two-stage trials. In our research, we address sample size recalculation in three-stage trials, i.e. trials with two pre-planned interim analyses. We show how recalculation rules from two-stage trials can be modified to be applicable to three-stage trials. We also illustrate how a performance measure, recently suggested for two-stage trial recalculation (the conditional performance score) can be applied to evaluate recalculation rules in three-stage trials, and we describe performance evaluation in those trials from the global point of view. To assess the potential of recalculation in three-stage trials, we compare, in a simulation study, two-stage group sequential designs with three-stage group sequential designs as well as multiple three-stage designs with recalculation. While we observe a notable favorable effect in terms of power and expected sample size by using three-stage designs compared to two-stage designs, the benefits of recalculation rules appear less clear and are dependent on the performance measures applied. Sample size recalculation is also applicable in three-stage designs. However, the extent to which recalculation brings benefits depends on which trial characteristics are most important to the applicants.
Sections du résumé
BACKGROUND
BACKGROUND
In clinical trials, the determination of an adequate sample size is a challenging task, mainly due to the uncertainty about the value of the effect size and nuisance parameters. One method to deal with this uncertainty is a sample size recalculation. Thereby, an interim analysis is performed based on which the sample size for the remaining trial is adapted. With few exceptions, previous literature has only examined the potential of recalculation in two-stage trials.
METHODS
METHODS
In our research, we address sample size recalculation in three-stage trials, i.e. trials with two pre-planned interim analyses. We show how recalculation rules from two-stage trials can be modified to be applicable to three-stage trials. We also illustrate how a performance measure, recently suggested for two-stage trial recalculation (the conditional performance score) can be applied to evaluate recalculation rules in three-stage trials, and we describe performance evaluation in those trials from the global point of view. To assess the potential of recalculation in three-stage trials, we compare, in a simulation study, two-stage group sequential designs with three-stage group sequential designs as well as multiple three-stage designs with recalculation.
RESULTS
RESULTS
While we observe a notable favorable effect in terms of power and expected sample size by using three-stage designs compared to two-stage designs, the benefits of recalculation rules appear less clear and are dependent on the performance measures applied.
CONCLUSIONS
CONCLUSIONS
Sample size recalculation is also applicable in three-stage designs. However, the extent to which recalculation brings benefits depends on which trial characteristics are most important to the applicants.
Identifiants
pubmed: 39322963
doi: 10.1186/s12874-024-02337-9
pii: 10.1186/s12874-024-02337-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
214Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : RA 2347/4-2
Organisme : Deutsche Forschungsgemeinschaft
ID : RA 2347/4-2
Organisme : Deutsche Forschungsgemeinschaft
ID : KI 708/4-2
Organisme : Deutsche Forschungsgemeinschaft
ID : KI 708/4-2
Organisme : Deutsche Forschungsgemeinschaft
ID : RA 2347/4-2
Informations de copyright
© 2024. The Author(s).
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