The performance of a Bayesian value-based sequential clinical trial design in the presence of an equivocal cost-effectiveness signal: evidence from the HERO trial.
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:
19 Jul 2024
19 Jul 2024
Historique:
received:
23
08
2023
accepted:
17
05
2024
medline:
20
7
2024
pubmed:
20
7
2024
entrez:
19
7
2024
Statut:
epublish
Résumé
There is increasing interest in the capacity of adaptive designs to improve the efficiency of clinical trials. However, relatively little work has investigated how economic considerations - including the costs of the trial - might inform the design and conduct of adaptive clinical trials. We apply a recently published Bayesian model of a value-based sequential clinical trial to data from the 'Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis' (HERO) trial. Using parameters estimated from the trial data, including the cost of running the trial, and using multiple imputation to estimate the accumulating cost-effectiveness signal in the presence of missing data, we assess when the trial would have stopped had the value-based model been used. We used re-sampling methods to compare the design's operating characteristics with those of a conventional fixed length design. In contrast to the findings of the only other published retrospective application of this model, the equivocal nature of the cost-effectiveness signal from the HERO trial means that the design would have stopped the trial close to, or at, its maximum planned sample size, with limited additional value delivered via savings in research expenditure. Evidence from the two retrospective applications of this design suggests that, when the cost-effectiveness signal in a clinical trial is unambiguous, the Bayesian value-adaptive design can stop the trial before it reaches its maximum sample size, potentially saving research costs when compared with the alternative fixed sample size design. However, when the cost-effectiveness signal is equivocal, the design is expected to run to, or close to, the maximum sample size and deliver limited savings in research costs.
Sections du résumé
BACKGROUND
BACKGROUND
There is increasing interest in the capacity of adaptive designs to improve the efficiency of clinical trials. However, relatively little work has investigated how economic considerations - including the costs of the trial - might inform the design and conduct of adaptive clinical trials.
METHODS
METHODS
We apply a recently published Bayesian model of a value-based sequential clinical trial to data from the 'Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis' (HERO) trial. Using parameters estimated from the trial data, including the cost of running the trial, and using multiple imputation to estimate the accumulating cost-effectiveness signal in the presence of missing data, we assess when the trial would have stopped had the value-based model been used. We used re-sampling methods to compare the design's operating characteristics with those of a conventional fixed length design.
RESULTS
RESULTS
In contrast to the findings of the only other published retrospective application of this model, the equivocal nature of the cost-effectiveness signal from the HERO trial means that the design would have stopped the trial close to, or at, its maximum planned sample size, with limited additional value delivered via savings in research expenditure.
CONCLUSION
CONCLUSIONS
Evidence from the two retrospective applications of this design suggests that, when the cost-effectiveness signal in a clinical trial is unambiguous, the Bayesian value-adaptive design can stop the trial before it reaches its maximum sample size, potentially saving research costs when compared with the alternative fixed sample size design. However, when the cost-effectiveness signal is equivocal, the design is expected to run to, or close to, the maximum sample size and deliver limited savings in research costs.
Identifiants
pubmed: 39030495
doi: 10.1186/s12874-024-02248-9
pii: 10.1186/s12874-024-02248-9
doi:
Substances chimiques
Hydroxychloroquine
4QWG6N8QKH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155Subventions
Organisme : UK National Institute for Health Research (NIHR)
ID : CTU Support Funding scheme (2019 call)
Organisme : UK National Institute for Health Research (NIHR)
ID : CTU Support Funding scheme (2019 call)
Organisme : UK National Institute for Health Research (NIHR)
ID : CTU Support Funding scheme (2019 call)
Organisme : UK National Institute for Health Research (NIHR)
ID : CTU Support Funding scheme (2019 call)
Organisme : UK National Institute for Health Research (NIHR)
ID : CTU Support Funding scheme (2019 call)
Organisme : UK National Institute for Health Research (NIHR)
ID : CTU Support Funding scheme (2019 call)
Informations de copyright
© 2024. The Author(s).
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