Clinical Trials in Sudden Cardiac Death Prevention: Principles and Endpoints

Chapter

Abstract

A properly designed and conducted randomized clinical trial is the most objective approach for definitive comparison of medical therapies. However, a clinical trial is a complex collaborative undertaking and requires substantial multidisciplinary planning efforts. This chapter presents the main components of a randomized trial and discusses the essential statistical concepts relevant in a trial design. The primary result and summary of statistical power, analysis, and the follow-up approach of the four recently completed pivotal clinical trials pertinent to the prevention of sudden cardiac death are summarized.

Keywords

Randomized controlled trial Intention-to-treat principle Informed consent Data Safety Monitoring Board Type I error Primary endpoint test statistic Treatment effect Statistical power Sample size Subgroup and interim analyses 

References

  1. 1.
    Friedman L, Furberg CD, DeMets DL. Fundamentals of clinical trials. 4th ed. New York: Springer; 2010.CrossRefGoogle Scholar
  2. 2.
    Piantadosi S. Clinical trials: a methodologic perspective. 2nd ed. Hoboken: Wiley; 2005.CrossRefGoogle Scholar
  3. 3.
    Chow SC, Liu JP. Design and analysis of clinical trials: concepts and methodologies. Hoboken: Wiley; 2004.Google Scholar
  4. 4.
    Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing clinical research. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2007.Google Scholar
  5. 5.
    Cook TD, DeMets DL, editors. Introduction to statistical methods for clinical trials. Boca Raton: Chapman & Hall; 2008.Google Scholar
  6. 6.
    Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH, for the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005; 352:225–37.Google Scholar
  7. 7.
    Boyle CA, Decoufle P. National sources of vital status information extent of coverage and possible selectivity in reporting. Am J Epidemiol. 1990;131:160–8.PubMedGoogle Scholar
  8. 8.
    National Research Council. The prevention and treatment of missing data in clinical trials. Panel on handling missing data in clinical trials. Committee on National Statistics. In: DoBaSSa, editor. Education. Washington, DC: The National Academies Press; 2010.Google Scholar
  9. 9.
    DeMets DL, Furberg CD, Friedman LM, editors. Data monitoring in clinical trials: a case studies approach. New York: Springer; 2006.Google Scholar
  10. 10.
    Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The cardiac arrhythmia suppression trial. N Engl J Med. 1991;324:781–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Al-Khatib SM, Sanders GD, Mark DB, Lee KL, Bardy GH, Bigger JT, et al. Implantable cardioverter defibrillators and cardiac resynchronization therapy in patients with left ventricular dysfunction: randomized trial evidence through 2004. Am Heart J. 2005;149:1020–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Chow SC, Chang M. Adaptive design methods in clinical trials. 2nd ed. New York: Chapman & Hall/CRC; 2011.Google Scholar
  13. 13.
    Fleming TR. Standard versus adaptive monitoring procedures: a commentary. Stat Med. 2006;25:3305–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Proschan MA, Lan KKG, Wittes JT. Statistical monitoring of clinical trials: a unified approach. New York: Springer; 2006.Google Scholar
  15. 15.
    Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med. 1999;341:1882–90.PubMedCrossRefGoogle Scholar
  16. 16.
    Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:877–83.PubMedCrossRefGoogle Scholar
  17. 17.
    Kadish A, Dyer A, Daubert JP, Quigg R, Estes NA, Anderson KP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004;350:2151–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Liu MB, Davis K. A clinical trials manual from The Duke Clinical Research Institute: lessons from a Horse Named Jim. 2nd ed. Hoboken: Wiley-Blackwell; 2010.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department of Biostatistics and BioinformaticsDuke University School of Medicine, Duke Clinical Research InstituteDurhamUSA

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