In:
Clinical Trials, SAGE Publications, Vol. 15, No. 5 ( 2018-10), p. 452-461
Abstract:
Well-designed phase II trials must have acceptable error rates relative to a pre-specified success criterion, usually a statistically significant p-value. Such standard designs may not always suffice from a clinical perspective because clinical relevance may call for more. For example, proof-of-concept in phase II often requires not only statistical significance but also a sufficiently large effect estimate. Purpose We propose dual-criterion designs to complement statistical significance with clinical relevance, discuss their methodology, and illustrate their implementation in phase II. Methods Clinical relevance requires the effect estimate to pass a clinically motivated threshold (the decision value (DV)). In contrast to standard designs, the required effect estimate is an explicit design input, whereas study power is implicit. The sample size for a dual-criterion design needs careful considerations of the study’s operating characteristics (type I error, power). Results Dual-criterion designs are discussed for a randomized controlled and a single-arm phase II trial, including decision criteria, sample size calculations, decisions under various data scenarios, and operating characteristics. The designs facilitate GO/NO-GO decisions due to their complementary statistical–clinical criterion. Limitations While conceptually simple, implementing a dual-criterion design needs care. The clinical DV must be elicited carefully in collaboration with clinicians, and understanding similarities and differences to a standard design is crucial. Conclusion To improve evidence-based decision-making, a formal yet transparent quantitative framework is important. Dual-criterion designs offer an appealing statistical–clinical compromise, which may be preferable to standard designs if evidence against the null hypothesis alone does not suffice for an efficacy claim.
Type of Medium:
Online Resource
ISSN:
1740-7745
,
1740-7753
DOI:
10.1177/1740774518770661
Language:
English
Publisher:
SAGE Publications
Publication Date:
2018
detail.hit.zdb_id:
2159773-X
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