Assessment of Consistency of Treatment Effects in Multiregional Clinical Trials

• Published in: Drug information journal 2010-09, Vol.44 (5), p.617-632
• Main Authors: Quan, Hui, Li, Mingyu, Chen, Joshua, Gallo, Paul, Binkowitz, Bruce, Ibia, Ekapimo, Tanaka, Yoko, Ouyang, Soo Peter, Luo, Xiaolong, Li, Gang, Menjoge, Shailendra, Talerico, Steven, Ikeda, Kimitoshi
• Format: Article
• Language: English
• Subjects: Biostatistics; Clinical medicine; Clinical trials; Drug Safety and Pharmacovigilance; Methods; Pharmaceuticals; Pharmacotherapy; Pharmacy; Sample size; Studies
• ISSN: 2168-4790; 0092-8615; 2168-4804; 2164-9200
• DOI: 10.1177/009286151004400509

Multiregional clinical trials (MRCTs) present great opportunities but also challenges to the trial community. To address the challenges and fully realize the opportunities, a PhRMA MRCT Cross-Functional Key Issue Team (KIT) was formed in 2008. One of the work streams within the KIT particularly focuses on the assessment of consistency of treatment effects across regions. As the main objective of this work stream, this research explores a number of definitions for consistency assessments. We address the issues primarily for superiority trials with continuous endpoints, then extend briefly to noninferiority trials, random effect models, binary endpoints, and survival endpoints. Computations and simulations are used to study the properties of the proposed definitions, particularly the power for showing consistency. To illustrate applications of the methods, we use a trial example with a continuous endpoint. We discuss considerations for trial design as well as for data analysis. The consistency assessment relies heavily on the definition of regions and the number of regions. We recommend working with health authorities to define region in a manner that is sensible from a practical interpretation standpoint and also makes region consistency assessment a feasible undertaking.