title: A portfolio-based approach to optimize proof-of-concept clinical trials.
abstract: Improving proof-of-concept (PoC) studies is a primary lever for improving drug development. Since drug development is often done by institutions that work on multiple drugs simultaneously, the present work focused on optimum choices for rates of false positive (α) and false negative (β) results across a portfolio of PoC studies. Simple examples and a newly derived equation provided conceptual understanding of basic principles regarding optimum choices of α and β in PoC trials. In examples that incorporated realistic development costs and constraints, the levels of α and β that maximized the number of approved drugs and portfolio value varied by scenario. Optimum choices were sensitive to the probability the drug was effective and to the proportion of total investment cost prior to establishing PoC. Results of the present investigation agree with previous research in that it is important to assess optimum levels of α and β. However, the present work also highlighted the need to consider cost structure using realistic input parameters relevant to the question of interest.
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285, USA. cmallinc@lilly.com
authors.forename: Craig
authors.initials: C
authors.lastname: Mallinckrodt
authors.forename: Geert
authors.initials: G
authors.lastname: Molenberghs
authors.forename: Charles
authors.initials: C
authors.lastname: Persinger
authors.forename: Stephen
authors.initials: S
authors.lastname: Ruberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Sashegyi
authors.forename: Stacy
authors.initials: S
authors.lastname: Lindborg
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D019317:Evidence-Based Medicine / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D008954:Models, Biological; D016896:Treatment Outcome