Biomarker threshold adaptive designs for survival endpoints. Issue 6 (2nd November 2018)

• Record Type: Journal Article
• Authors: Diao, Guoqing; Dong, Jun; Zeng, Donglin; Ke, Chunlei; Rong, Alan; Ibrahim, Joseph G
• Is Part Of: Journal of biopharmaceutical statistics. Volume 28:Issue 6(2018)
• Page Start: 1038
• Page End: 1054
• Publication Date: 2018-11-02
• Subjects: Adaptive enrichment design -- predictive biomarker -- survival endpoint -- two-stage design; Pharmacy -- Statistical methods -- Periodicals; Drugs -- Testing -- Statistical methods -- Periodicals; Biometry -- Periodicals; Biopharmaceutics -- Periodicals; Pharmacokinetics -- Periodicals; 615.19
• DOI: 10.1080/10543406.2018.1434191
• Languages: English
• ISSNs: 1054-3406

Abstract

ABSTRACT: Due to the importance of precision medicine, it is essential to identify the right patients for the right treatment. Biomarkers, which have been commonly used in clinical research as well as in clinical practice, can facilitate selection of patients with a good response to the treatment. In this paper, we describe a biomarker threshold adaptive design with survival endpoints. In the first stage, we determine subgroups for one or more biomarkers such that patients in these subgroups benefit the most from the new treatment. The analysis in this stage can be based on historical or pilot studies. In the second stage, we sample subjects from the subgroups determined in the first stage and randomly allocate them to the treatment or control group. Extensive simulation studies are conducted to examine the performance of the proposed design. Application to a real data example is provided for implementation of the first-stage algorithms.