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Interim Evaluation of Efficacy in Clinical Trials with Two Primary Endpoints

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Group-Sequential Clinical Trials with Multiple Co-Objectives

Part of the book series: SpringerBriefs in Statistics ((JSSRES))

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Abstract

In this chapter, we provide an overview of the fundamental concepts and technical details for group-sequential designs for clinical trials comparing two interventions based on two primary endpoints. In this situation, there are many procedures for controlling the Type I error rate. We discuss the simplest procedure, i.e., the weighted Bonferroni procedure which is commonly applied in practice. We evaluate the behavior of the sample size, power, and Type I error rate associated with the procedure.

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References

  • Berger RL (1982) Multiparameter hypothesis testing and acceptance sampling. Technometrics 24:295–300

    Article  MathSciNet  MATH  Google Scholar 

  • Bretz F, Maurer W, Brannath W, Posch M (2009) A graphical approach to sequentially rejective multiple test procedures. Stat Med 28:586–604

    Article  MathSciNet  Google Scholar 

  • Bretz F, Hothorn T, Westfall P (2011) Multiple comparisons using R. Chapman and Hall, CRC Press, Boca Raton

    MATH  Google Scholar 

  • Burman CF, Sonesson C, Guilbaud O (2009) A recycling framework for the construction of Bonferroni-based multiple tests. Stat Med 28:739–761

    Article  MathSciNet  Google Scholar 

  • Dmitrienko A, Tamhane AC, Bretz F (2010) Multiple testing problems in pharmaceutical statistics. Chapman and Hall, CRC Press, Boca Raton

    Google Scholar 

  • Glimm E, Mauer W, Bretz F (2009) Hierarchical testing of multiple endpoints in group-sequential trials. Stat Med 29:219–228

    MathSciNet  Google Scholar 

  • Glimm E, Mauer W, Bretz F (2010) Hierarchical testing of multiple endpoints in group-sequential trials. Stat Med 29:219–228

    MathSciNet  Google Scholar 

  • Hung HMJ, Wang SJ, O’Neill RT (2007) Statistical considerations for testing multiple endpoints in group sequential or adaptive clinical trials. J Biopharm Stat 17:1201–1210

    Article  MathSciNet  Google Scholar 

  • Jennison C, Turnbull BW (1991) Exact calculations for sequential t, χ 2 and F tests. Biometrika 78:133–141

    MathSciNet  MATH  Google Scholar 

  • Jennison C, Turnbull BW (2000) Group sequential methods with applications to clinical trials. Chapman and Hall, CRC Press, Boca Raton

    MATH  Google Scholar 

  • Kosorok MR, Shi Y, DeMets DL (2004) Design and analysis of group-sequential clinical trials with multiple primary endpoints. Biometrics 60:134–145

    Google Scholar 

  • Lan KKG, DeMets DL (1984) Discrete sequential boundaries for clinical trials. Biometrika 70:659–663

    Google Scholar 

  • Maurer W, Bretz F (2013) Multiple testing in group sequential trials using graphical approaches. Stat Biopharm Res 5:311–320

    Article  Google Scholar 

  • O’Brien PC (1984) Procedures for comparing samples with multiple endpoints. Biometrics 40:1079–1087

    Article  MathSciNet  Google Scholar 

  • O’Brien PC, Fleming TR (1979) A multiple testing procedure for clinical trials. Biometrics 35:549–556

    Article  Google Scholar 

  • Pocock SJ (1977) Group sequential methods in the design and analysis of clinical trials. Biometrika 64:191–199

    Article  Google Scholar 

  • Pocock SJ, Geller NL, Tsiatis AA (1987) The analysis of multiple endpoints in clinical trials. Biometrics 43:487–498

    Article  MathSciNet  Google Scholar 

  • Senn S, Bretz F (2007) Power and sample size when multiple endpoints are considered. Pharm Stat 6:161–170

    Article  Google Scholar 

  • Sozu T, Sugimoto T, Hamasaki T, Evans SR (2015) Sample size determination in clinical trials with multiple endpoints. Springer International Press, Cham

    Book  MATH  Google Scholar 

  • Tamhane AC, Mehta CR, Liu L (2010) Testing a primary and secondary endpoint in a group sequential design. Biometrics 66:1174–1184

    Article  MathSciNet  MATH  Google Scholar 

  • Tamhane AC, Wu Y, Mehta C (2012) Adaptive extensions of a two-stage group sequential procedure for testing primary and secondary endpoints (I): unknown correlation between the endpoints. Stat Med 31:2027–2040

    Article  MathSciNet  Google Scholar 

  • Tang DI, Geller NL (1999) Closed testing procedures for group sequential clinical trials with multiple endpoints. Biometrics 55:1188–1192

    Article  MATH  Google Scholar 

  • Tang DI, Gnecco C, Geller NL (1989) Design of group sequential clinical trials with multiple endpoints. J Am Stat Assoc 84:776–779

    Article  Google Scholar 

  • Wiens BL, Dmitrienko A (2010) On selecting a multiple comparison procedure for analysis of a clinical trial: fallback, fixed sequence, and related procedures. Stat Biopharm Res 2:22–32

    Article  Google Scholar 

  • Xi D, Tamhane AC (2015) Allocating recycled significance levels in group sequential procedures for multiple endpoints. Biometrical J 57:90–107

    Article  MathSciNet  MATH  Google Scholar 

  • Ye Y, Li A, Lui L, Yao B (2013) A group sequential Holm procedure with multiple primary endpoints. Stat Med 32:1112–1124

    Article  MathSciNet  Google Scholar 

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Authors and Affiliations

  1. Department of Data Science, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan

    Toshimitsu Hamasaki

  2. Department of Data Science, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan

    Koko Asakura

  3. Department of Biostatistics and the Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Scott R. Evans

  4. Biostatistics Department, Shionogi & Co., Ltd., Osaka, Japan

    Toshimitsu Ochiai

Authors
  1. Toshimitsu Hamasaki
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  2. Koko Asakura
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  3. Scott R. Evans
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  4. Toshimitsu Ochiai
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Corresponding author

Correspondence to Toshimitsu Hamasaki .

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Hamasaki, T., Asakura, K., Evans, S.R., Ochiai, T. (2016). Interim Evaluation of Efficacy in Clinical Trials with Two 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_5

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