Applicability of a Pick a Winner trial design to acute myeloid leukemia

Randomized clinical trials remain the gold standard to establish efficacy and safety of new treatments. In acute myeloid leukemia, large trials have been associated with gradual improvement in outcome over 2 decades in younger patients without major differences emerging between treatments. By contrast, in older patients, improvement has been minimal, which justifies a new approach to identifying effective treatments. Given the urgent un-met need, and with the emergence of several novel agents or combinations that are likely to be expensive, large benefits are probably required to change clinical practice. To address this issue, we have evolved a Pick a Winner randomized progressive design with a rolling incorporation of novel treatments (drug X), which has been tested in older patients with acute myeloid leukemia. The rationale, operational characteristics, and initial experience of such an approach in the context of the United Kingdom National Cancer Research Institute AML16 trial are presented. (Blood. 2011;118(9):2389-2394)