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Optimal planning of phase II/III programs for clinical trials with multiple endpoints
Author(s) -
Kieser Meinhard,
Kirchner Marietta,
Dölger Eva,
Götte Heiko
Publication year - 2018
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.1861
Subject(s) - context (archaeology) , phase (matter) , computer science , clinical trial , sample size determination , drug development , sample (material) , phases of clinical research , operations research , medical physics , risk analysis (engineering) , statistics , medicine , mathematics , drug , pharmacology , paleontology , chemistry , biology , organic chemistry , chromatography
Summary Owing to increased costs and competition pressure, drug development becomes more and more challenging. Therefore, there is a strong need for improving efficiency of clinical research by developing and applying methods for quantitative decision making. In this context, the integrated planning for phase II/III programs plays an important role as numerous quantities can be varied that are crucial for cost, benefit, and program success. Recently, a utility‐based framework has been proposed for an optimal planning of phase II/III programs that puts the choice of decision boundaries and phase II sample sizes on a quantitative basis. However, this method is restricted to studies with a single time‐to‐event endpoint. We generalize this procedure to the setting of clinical trials with multiple endpoints and (asymptotically) normally distributed test statistics. Optimal phase II sample sizes and go/no‐go decision rules are provided for both the “all‐or‐none” and “at‐least‐one” win criteria. Application of the proposed method is illustrated by drug development programs in the fields of Alzheimer disease and oncology.