American Heart Journal
Volume 155, Issue 1 , Pages 33-41 , January 2008

Monitoring the ACTIVE-W trial: Some issues in monitoring a noninferiority trial

  • John A. Cairns, MD

      Affiliations

    • University of British Columbia, Vancouver, British Columbia, Canada
    • Corresponding Author InformationReprint requests: John Cairns, MD, GLD Health Care Centre, 2775 Laurel St, Rm 9113, Vancouver, British Columbia, Canada V5Z1M9.
    • ,
  • Janet Wittes, PhD

      Affiliations

    • Statistics Collaborative, Inc., Washington, DC
    • ,
  • D. George Wyse, MD, PhD

      Affiliations

    • Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada
    • ,
  • Janet Pogue, MSc

      Affiliations

    • McMaster University, Hamilton, Ontario, Canada
    • ,
  • Michael Gent, DSc

      Affiliations

    • McMaster University, Hamilton, Ontario, Canada
    • ,
  • Jack Hirsh, MD

      Affiliations

    • McMaster University, Hamilton, Ontario, Canada
    • ,
  • John Marler, MD

      Affiliations

    • National Institute of Neurological Disorders and Stroke, Bethesda, MD
    • ,
  • Edward L.C. Pritchett, MD

      Affiliations

    • Duke University, Durham, NC

Received 29 May 2007 ,Accepted 4 September 2007.

References 

  1. ACTIVE Writing Group on behalf of the ACTIVE InvestigatorsConnolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomized controlled trial. Lancet. 2006;367:1903–1912
  2. Wittes J. Active-control trials—a linguistic problem. Int Chin Stat Soc Bull. 2001;39–40
  3. D'Agostino RB, Massaro JM, Sullivan LM. Non-inferiority trials: design concepts and issues—the encounters of academic consultants in statistics. Stat Med. 2003;22:169–186
  4. Lange S, Freitag G. Choice of delta: requirements and reality—results of a systematic review. Biometrical J. 2005;1:12–27
  5. Piaggio G, Elbourne DR, Altman DG, et al. for the CONSORT Group Reporting of noninferiority and equivalence randomized trials. An extension of the CONSORT Statement. JAMA. 2006;295:1152–1160
  6. Kaul S, Diamond GA, Weintraub WS. Trials and tribulations of non-inferiority. The ximelagatran experience. J Am Coll Cardiol. 2005;46:1986–1995
  7. Kaul S, Diamond GA. Making sense of noninferiority: a clinical and statistical perspective on its application to cardiovascular clinical trials. Progr Cardiovasc Dis. 2007;49:284–299
  8. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991;324:781–788
  9. DeMets DL, Friedman LM. The data monitoring experience in the Cardiac Arrhythmia Suppression Trial: the need to be prepared early. In:  DeMets DL,  Furberg CD,  Friedman LM editor. Data monitoring in clinical trials. New York (NY): Springer; 2006;p. 198–208
  10. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321–333
  11. Lan KK, Simon R, Halperin M. Stochastically curtailed sampling in long-term clinical trials. Commun Stat Theory Methods. 1984;13:2339–2353
  12. Lan KK, Wittes J. The B-value: a tool for monitoring data. Biometrics. 1988;44:579–585
  13. Ware JH, Muller JE, Braunwald E. The futility index. An approach to the cost-effective termination of randomized clinical trials. Am J Med. 1985;78:635–643
  14. Lachin JM. A review of methods for futility stopping based on conditional power. Statis Med. 2005;24:2747–2764
  15. Freemantle N, Calvert M, Wood J, et al. Composite outcomes in randomized trials. Greater precision but with greater uncertainty?. JAMA. 2003;289:2554–2559
  16. Montori VM, Permanyer-Miralda , Ferreira-Gonzalez , et al. Validity of composite end points in clinical trials. BMJ. 2005;330:594–596
  17. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355:2203–2216
  18. Pocock SJ. Current controversies in data monitoring for clinical trials. Clin Trials. 2006;3:513–521

 Funding of ACTIVE-W (Clinical Trials.gov, number NCT00243178) by Sanofi-Aventis and Bristol-Myers Squibb. No funding requested or provided for the present publication.

 Conflicts of interest: all coauthors were members of the ACTIVE-W DSMB and received honoraria for their participation. Cairns, Wittes, Pogue, Gent, Hirsh, Pritchett—none additional; Wyse—Scientific Advisory Board Sanofi Aventis; Hirsh—consulted on clopidogrel, chaired advisory boards for Bristol-Myers Squibb.

PII: S0002-8703(07)00775-2

doi: 10.1016/j.ahj.2007.09.011

American Heart Journal
Volume 155, Issue 1 , Pages 33-41 , January 2008

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