  Background: 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). 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.
  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.
