ABSTRACT
Adaptive Trial? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487 22.2 Planning an Adaptive Clinical Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489
22.2.1 Simulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489 22.2.2 Discussions with the Regulators . . . . . . . . . . . . . . . . . . . . . . . . . 490
22.3 Executing an Adaptive Clinical Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492 22.3.1 Managing Investigators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492 22.3.2 Extracting the Clinical Data for Analysis . . . . . . . . . . . . . . . 494 22.3.3 Preparing for Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496 22.3.4 The DMC’s Role and the DMC Charter . . . . . . . . . . . . . . . . 499 22.3.5 Third Parties: The Multiple CRO Ecosystem . . . . . . . . . . . 501 22.3.6 Managing the Risks in an Adaptive Design . . . . . . . . . . . . . 502
22.4 In Summary: A Challenge Worth Taking . . . . . . . . . . . . . . . . . . . . . . . . 503 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
Dose-response adaptive clinical trials (with multiple doses) are perhaps the most difficult adaptive trial to implement, but they are the best designs for minimising the risks of making wrong decisions about the drug. People are naturally more apprehensive of “unknown unknowns” than they are of “known unknowns” (to borrow the phrases made famous by Donald Rumsfeld). So whilst in this chapter we offer some experience of overcoming the difficulties
of implementing dose-response adaptive trials, possibly the greater value in this chapter is simply the description of what all the difficulties are. So the “unknowns” become “known”.
