Table 2.

Study Design Issues Identified During Trial Planning and Types of Adaptive Designs to Potentially Address These Issues

Study Design Issue Identified in Trial Planning	Adaptive Design to Potentially Address the Issuea
Imprecise estimate of control group response rate or variation in responses	Sample size adjustment
Imprecise magnitude and/or precision of effect size	Sample size adjustment Predicted intervals
Uncertainty regarding subjects most likely to experience a benefit or a toxicity	Population enrichment
Uncertainty regarding the optimal dose of a new drug to assess its efficacy	Seamless phase II/III trial; multiarm, multistage trial
Multiple drugs, drug combinations, or treatment or testing strategies need to be evaluated in a consistent and efficient manner	Multiarm, multistage trial; platform trial
Uncommon or rare condition makes it difficult to recruit sufficient subjects	Umbrella or basket trial
Uncertainty or evolution in optimal end point(s) to evaluate efficacy or safety	Changing end points

^aSee text for discussion of the advantages and limitations of specific designs.