Sample Size Determination in Clinical Trials with Multiple Correlated Endpoints

• Activity Number: 606
• Type: Topic Contributed
• Date/Time: Thursday, August 2, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Toshimitsu Hamasaki*+ and Takashi Sozu and Tomoyuki Sugimoto and Scott Evans
• Companies: Osaka University Graduate School of Medicine and Kyoto University and Hirosaki University and Harvard University
• Keywords: Clinical Trials ; Conjunctive Power ; Disjunctive Power ; Multiplicity ; Multipe Endpoints ; Sample Size

Abstract

The determination of sample size and the evaluation of power are critical elements in the design of a clinical trial. Most commonly, a single outcome is selected as the primary endpoint and is used as the basis for the trial design including sample size determination, as well as for interim monitoring and final analyses. However, many recent clinical trials have utilized more than one primary endpoint potentially offering a more complete characterization of intervention effects. Use of multiple endpoints creates complexities in the evaluation of power and sample size in the planning of clinical trials, specifically relating to control of the Type I or II errors when potential correlation among the outcomes is possible. We describe an approach to the evaluation of power and sample size in superiority/non-inferiority clinical trials with multiple primary endpoints. We first discuss simple situations, in which all outcomes are of a common scale, i.e., (i) all continuous, (ii) all binary and (iii) all time-to-event form. We then discuss more complex situations where endpoint scales are mixed, i.e., (iv) continuous and binary, and (v) time-to-event and binary endpoints.