This article focuses on statistical analysis of clinical trials pursuing tailored therapy objectives, wherein evaluation of treatment effect occurs in the overall population as well as in a predefined subpopulation(s). The design and analysis principles presented provide a framework for decision making based on these novel multipopulation tailoring trial designs, considering the particular case of confirmatory trials. These principles include traditional multiple testing considerations, as well as 2 new analysis principles.
CappuzzoFCiuleanuTStelmakhL. SATURN: a double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC. J Clin Oncol. 2009;27(15 S):8001.
7.
WangSO’NeillRHungH. Approaches to evaluation of treatment effect in randomized clinical trials with genomic subset. Pharm Stat. 2007;6:227–244.
8.
WangSHungHO’NeillR. Adaptive patient enrichment designs in therapeutic trials. Biom J. 2009;51:358–374.
9.
SongYChiGY. A method for testing a prespecified subgroup in clinical trials. Stat Med. 2007;26:3535–3549.
10.
AloshMHuqueM. A flexible strategy for testing subgroups and overall population. Stat Med. 2009;28:3–23.
11.
ZhaoYDDmitrienkoATamuraR. On optimal designs of clinical trials with a sensitive subgroup. Stat Biopharm Res. 2010;2:72–83.
12.
FreidlinBSimonR. Adaptive signature design: an adaptive clinical trial design for generating and prospectively testing a gene expression signature for sensitive patients. Clin Cancer Res. 2005;11:7872–7878.
13.
JiangWFreidlinBSimonR. Biomarker-adaptive threshold design: a procedure for evaluating treatment with possible biomarker-defined subset effect. J Natl Cancer Inst. 2007;99:1036–1043.
14.
DmitrienkoABretzFWestfallPH. Multiple testing methodology. In:
DmitrienkoATamhaneACBretzF, eds. Multiple Testing Problems in Pharmaceutical Statistics. New York, NY: Chapman and Hall/CRC Press; 2009:35–98.
15.
WiensB. A fixed-sequence Bonferroni procedure for testing multiple endpoints. Pharm Stat. 2003;2:211–215.
16.
WiensBDmitrienkoA. The fallback procedure for evaluating a single family of hypotheses. J Biopharm Stat. 2003;15:929–942.
17.
HuqueMFAloshM. A flexible fixed-sequence testing method for hierarchically ordered correlated multiple endpoints in clinical trials. J Stat Plann Inference. 2008;138:321–335.
18.
MillenBADmitrienkoA. Chain procedures: a class of flexible closed testing procedures with clinical trial applications. Stat Biopharm Res. 2011;3:14–30.
19.
BretzFMaurerWBrannathWPoschM. A graphical approach to sequentially rejective multiple test procedures. Stat Med. 2009;28:586–604.
20.
BurmanCFSonessonCGuilbaudO. A recycling framework for the construction of Bonferroni-based multiple tests. Stat Med. 2009;28:739–761.
21.
GailMSimonR. Testing for qualitative interactions between treatment effects and patient subsets. Biometrics. 1985;41:361–372.
22.
PiantadosiSGailMH. A comparison of the power of two tests for qualitative interaction. Stat Med. 1993;12:1239–1248.
