Abstract
We discuss group-sequential designs for early efficacy or futility stopping in superiority clinical trials with multiple co-primary endpoints. We discuss several decision-making frameworks for evaluating efficacy or futility based on boundaries using group-sequential methodology. We incorporate the correlations among the endpoints into the calculations for futility critical boundaries and evaluate the required sample sizes as a function of design parameters including mean differences, the number of planned analyses, and efficacy critical boundaries. We provide an example to illustrate the methods and discuss practical considerations when designing efficient group-sequential designs in clinical trials with co-primary endpoints.
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References
Ando Y, Hamasaki T, Evans SR, Asakura K, Sugimoto T, Sozu T, Ohno Y (2015) Sample size considerations in clinical trials when comparing two interventions using multiple co-primary binary relative risk contrasts. Stat Biopharm Res 7:81–94
Asakura K, Hamasaki T, Sugimoto T, Hayashi K, Evans SR, Sozu T (2014) Sample size determination in group-sequential clinical trials with two co-primary endpoints. Stat Med 33:2897–2913
Asakura K, Hamasaki T, Evans SR (2015) Interim evaluation of efficacy or futility in group-sequential clinical trials with multiple co-primary endpoints. The 2015 Joint Statistical Meetings, Seattle, USA, 8–13 August
Chang MN, Hwang IK, Shih WJ (1998) Group sequential designs using both Type I and Type II error probability spending functions. Commun Stat Theor Methods 27:1323–1339
Cheng Y, Ray S, Chang M, Menon S (2014) Statistical monitoring of clinical trials with multiple co-primary endpoints using multivariate B-value. Stat Biopharm Res 6:241–250
Chuang-Stein C, Stryszak P, Dmitrienko A, Offen W (2007) Challenge of multiple co-primary endpoints: a new approach. Stat Med 26:1181–1192
Cook RJ, Farewell VT (1994) Guideline for monitoring efficacy and toxicity responses in clinical trials. Biometrics 50s:1146–1162
DeMets DL, Ware JH (1980) Group sequential methods for clinical trials with a one-sided hypothesis. Biometrika 67:651–660
DeMets DL, Ware JH (1982) Asymmetric group sequential boundaries for monitoring clinical trials. Biometrika 69:661–663
Gould AL, Pecore VJ (1982) Group sequential methods for clinical trials allowing early acceptance of H0 and incorporating costs. Biometrika 69:75–80
Green R, Schneider LS, Amato DA, Beelen AP, Wilcock G, Swabb EA, Zavitz KH, for the Tarenflurbil Phase 3 Study Group (2009) Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. J Am Med Assoc 302:2557–2564
Hamasaki T, Asakura K, Evans SR, Sugimoto T, Sozu T (2015) Group-sequential strategies in clinical trials with multiple co-primary outcomes. Stat Biopharm Res 7:36–54
Jennison C, Turnbull BW (1993) Group sequential tests for bivariate response: interim analyses of clinical trials with both efficacy and safety. Biometrics 49:741–752
Kordzakhia G, Siddiqui O, Huque MF (2010) Method of balanced adjustment in testing co-primary endpoints. Stat Med 29:2055–2066
Lachin JM (2005) A review of methods for futility stopping based on conditional power. Stat Med 24:2747–2764
Lan KKG, DeMets DL (1983) Discrete sequential boundaries for clinical trials. Biometrika 70:659–663
Lan KKG, Simon R, Halperin M (1982) Stochastically curtailed tests in long-term clinical trials. Commun Stat Theor Methods 1:207–219
O’Brien PC, Fleming TR (1979) A multiple testing procedure for clinical trials. Biometrics 35:549–556
Pharmaceuticals and Medical Devices Agency (2010a) Review report of memantine. 1 Dec 2010, Pharmaceuticals and Medical Devices Agency, Tokyo (in Japanese). Available at: http://www.pmda.go.jp/drugs/2011/P201100018/43057400_22300AMX00423_A100_2.pdf. Accessed 25 Nov 2015
Pharmaceuticals and Medical Devices Agency (2010b) Review report of galantamine hydrobromide. 1 Dec 2010, Pharmaceuticals and Medical Devices Agency, Tokyo (in Japanese). Available at: http://www.pmda.go.jp/drugs/2011/P201100024/80015500_23000AMX00426_A100_1.pdf. Accessed 25 Nov 2015
Pharmaceuticals and Medical Devices Agency (2011) Review report of rivastigmine. 11 March 2011, Pharmaceuticals and Medical Devices Agency, Tokyo (in Japanese). Available at: http://www.pmda.go.jp/drugs/2011/P201100075/18018800_22300AMX00529000_A100_1.pdf. Accessed 25 Nov 2015
Snapinn S, Chen MG, Jiang Q, Koutsoukos T (2006) Assessment of futility in clinical trials. Pharm Stat 5:273–281
Ware JH, Muller JE, Braunwald E (1985) The futility index: an approach to the cost-effective termination of randomized clinical trials. Am J Med 78:635–643
Whitehead J, Matsushita T (2003) Stopping clinical trials because of treatment ineffectiveness: a comparison of a futility design with a method of stochastic curtailment. Stat Med 22:677–687
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Hamasaki, T., Asakura, K., Evans, S.R., Ochiai, T. (2016). Interim Evaluation of Efficacy or Futility in Clinical Trials with Two Co-primary Endpoints. In: Group-Sequential Clinical Trials with Multiple Co-Objectives. SpringerBriefs in Statistics(). Springer, Tokyo. https://doi.org/10.1007/978-4-431-55900-9_4
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DOI: https://doi.org/10.1007/978-4-431-55900-9_4
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