Consistency efficacy assessment of multi-regional clinical trials

Abstract

Abstract: The multi-regional clinical trials (MRCTs) have received wide attention with an increasing trend of globalization of clinical trials. A key issue in MRCTs is how to assess the consistency of treatment effect across regions. In this paper, we provide a systematic review of methods that be commonly used for assessing the consistency in MRCTs. We also give some simple discussion about the choice of methods of assessing the consistency of treatment effect across regions, such as the power of the test, the false-positive rate and the relationship between the type I error and the sample size. The purpose of this paper is to provide some reference for the members in designing and conducting MRCTs and offer some theory evidences of clinical trails for new drug development. We hope that more researchers can concern this study in this field, promoting the development of MRCTs in our country.

Key words: Multi-regional clinical trials (MRCTs), Consistency, Heterogeneity, Quantitative, Qualitative

CLC Number:

R969.4

WANG Fei, XIE Hai-tang, JIANG Bo, YAN Fang-rong. Consistency efficacy assessment of multi-regional clinical trials[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(10): 1126-1131.

References

[1] Blair JEA, Zannad F, Konstam MA,et al. Continental differences in clinical characteristics, management, and outcomes in patients hospitalized with worsening heart failure [J]. J Am Coll Cardiol,2008,52(20):1640-1648.
[2] Wedel H, DeMets D, Deedwania P, et al. Challenges of subgroup analyses in multinational clinical trials: experiences from the MERIT-HF trial[J]. Am Heart J, 2001, 142(3):502-511.
[3] Akkerhuis KM, Deckers JW, Boersma E, et al. Geographic variability in outcomes within an international trial of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes[J]. Eur Heart J Suppl, 2000, 21(5):371-381.
[4] Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses[J]. BMJ,2003, 327(7414):557-560.
[5] Der Simonian R, Laird N. Meta-analysis in clinical trials[J]. Control Clin Trials, 1986, 7(4):177-188.
[6] Fleiss. Analysis of data from multiclinic trials[J]. Control Clin Trials,1986, 7(4):267-275.
[7] Chow SC, Shao J, Hu YP. Assessing sensitivity and similarity in bridging studies[J]. J Biopharm Stat, 2002, 12(3):385-400.
[8] Gail M, Simon R. Testing for qualitative interaction between treatment effects and patient subsets[J]. Biometrics,1985, 41(2):361-372.
[9] Piantadosi S, Gail M. A comparison of the power of two tests for qualitative interactions[J]. Stat Med, 1993,12(13):1239-1248.
[10] Ciminera JL, Heyse JF, Nguyen HH, et al. Tests for qualitative treatment-by-centre interaction using a 'Pushback' procedure[J]. Stat Med, 1993, 12(11):1033-1045.
[11] Ministry of Health, Labour and Welfare of Japan. Basic Principles on Global Clinical Trials[S]. September 28, 2007.
[12] Kawai N. An approach to rationalize partitioning sample size into individual regions in a multiregional trial[J]. Drug Inf J, 2008, 42(2):139-147.
[13] Uesaka H. Sample size allocation to regions in a multiregional trial[J]. J Biopharm Stat, 2009, 19(4):580-594.
[14] FDA Medical Review of COZAARTM Tablets (Losartan Potassium). NDA 20-386/SE1-028[EB/OL]. Available at http://www.fda.gov/ohrms/dockets/ac/02/briefing/3849b1_03_medical-review.pdf. March 2002.
[15] Quan H, Li M, Chen J, et al. Assessment of consistency of treatment effects in multi-regional clinical trials[J]. Drug Inf J, 2010, 44(5):617-632.