title: Evaluation of program success for programs with multiple trials in binary outcomes.
abstract: A late-stage clinical development program typically contains multiple trials. Conventionally, the program's success or failure may not be known until the completion of all trials. Nowadays, interim analyses are often used to allow evaluation for early success and/or futility for each individual study by calculating conditional power, predictive power and other indexes. It presents a good opportunity for us to estimate the probability of program success (POPS) for the entire clinical development earlier. The sponsor may abandon the program early if the estimated POPS is very low and therefore permit resource savings and reallocation to other products. We provide a method to calculate probability of success (POS) at an individual study level and also POPS for clinical programs with multiple trials in binary outcomes. Methods for calculating variation and confidence measures of POS and POPS and timing for interim analysis will be discussed and evaluated through simulations. We also illustrate our approaches on historical data retrospectively from a completed clinical program for depression.
authors: Merck Research Laboratories, North Wales, PA, USA.
authors: Meihua
authors: M
authors: Wang
authors: Merck Research Laboratories, North Wales, PA, USA.
authors: G Frank
authors: GF
authors: Liu
authors: Merck Research Laboratories, North Wales, PA, USA.
authors: Jerald
authors: J
authors: Schindler
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D000077608:Aprepitant; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D003627:Data Interpretation, Statistical; D003863:Depression / Q000188:drug therapy; D017277:Drug Approval / Q000379:methods; D006801:Humans; D015233:Models, Statistical; D009025:Morpholines / Q000627:therapeutic use; D011336:Probability; D015397:Program Evaluation / Q000379:methods; D013223:Statistics as Topic / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D009025:Morpholines; D000077608:Aprepitant
keywords: binary outcomes; confidence measures; probability of program success; probability of success