ABSTRACT

Multiple-endpoint problems can arise in many different situations. For in-

stance, when there is a single primary efficacy endpoint with one or more

secondary endpoints, we try to claim the drug effect on primary and sec-

ondary endpoints; when there are two endpoints, at least one needs to be

statistically significant to claim efficacy of the test drug; in a clinical trial

we can use a surrogate endpoint for an accelerated approval and a clinically

important endpoint for a full approval. In this chapter, we will first review

the single-stage and stepwise methods in classical designs, then discuss

multiple-endpoint issues in adaptive designs. We will use trial examples to

give step by step instructions.