The randomized placebo-phase design for clinical trials

Randomized controlled trials are the criterion standard method for evaluati ng the effectiveness of medical treatments. There are situations, however, where the possibility of being in the control group in a randomized control led trial is unacceptable to potential subjects or their physicians. This l ack of acceptance is a reason for poor accrual. We developed and validated a new clinical trial design for survival data that may allay concerns about not receiving an investigational product and should be more acceptable. Ca lled the randomized placebo-phase design, this new design asks whether, on average, those subjects who begin active treatment sooner respond sooner th an those who begin it later. Using Monte Carlo computer simulations, we dem onstrated that the design is valid and may offer advantages over traditiona l randomized controlled trials in some situations. The randomized placebo-p hase design may be especially useful when highly potent therapies for rare diseases are tested or when accrual may be otherwise difficult. (C) 2001 El sevier Science Inc. All rights reserved.