Creating a synthetic control arm from previous clinical trials: Application to establishing early end points as indicators of overall survival in acute myeloid leukemia (AML).

7021Background: Clinical trials of experimental drugs require controls. Concurrently randomized controls are the gold standard for judging drug effect. Historical controls are not ideal but are much more efficient and economical. Historical controls derived from a single clinical trial have the biases of that trial. Using many trials with comparable end points and eligibility minimizes such bias. Medidata’s archive contains >3000 trials with clinical data rights for deidentified aggregated analyses. We used this resource to develop a synthetic control arm (SCA) for a particular phase I/II single-arm trial in AML. We demonstrate the utility of this approach by addressing a different but equally important issue: establishing early end points as predictors of long term clinical outcomes. Methods: We built an SCA from 7 relapsed/refractory AML trials completed in last 5 yrs. They had similar eligibility criteria as a particular phase I/II trial for an investigational agent. We selected subjects for the SCA wh...