Advertisement

Some Problems of Multiplicity in Long-Term Intervention Studies

  • Michael Gent
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 39)

Abstract

Much has been learned about the design and execution of long-term intervention studies from the experience with the recent major trials1–11 evaluating various platelet suppressing drugs in the secondary prevention of myocardial ischemia or cerebral ischemia. These studies have also served to highlight a number of misconceptions and oversights about statistical analysis and interpretation, particularly as they relate to the multiplicity of questions which, of necessity, must be asked of the data both as they accumulate and at the completion of the study.

Keywords

Sudden Death Arteriovenous Shunt Repeat Examination Study Research Group Coronary Drug Project 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    P.C. Elwood, A.L. Cochrane, M.L. Burr, P.M. Sweetnam, G. Williams, E. Welsby, S.J. Hughes and R. Renton, A randomized controlled clinical trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction, Br. Med. J. 1: 436 (1974).PubMedCrossRefGoogle Scholar
  2. 2.
    The Coronary Drug Project Research Group, Aspirin in coronary heart disease, J. Chronic. Pis. 29: 625 (1976).CrossRefGoogle Scholar
  3. 3.
    K. Breddin, Multicenter two-year prospective study on the prevention of secondary myocardial infarction by ASA in comparison with phenprocoumon and placebo, in: “Essais Controles Multicentres Principes et Problems,” J.P. Boissel and C.R. Klimt, eds., I.N.S.E.R.M., Paris (1979).Google Scholar
  4. 4.
    P.C. Elwood and P.M. Sweetnam, Aspirin and secondary mortality after myocardial infarction, Lancet ii: 1313 (1979).CrossRefGoogle Scholar
  5. 5.
    Aspirin Myocardial Infarction Study Research Group, A randomized controlled trial of aspirin in persons recovered from myocardial infarction, JAMA 243: 661 (1980).CrossRefGoogle Scholar
  6. 6.
    The Persantine - Aspirin Reinfarction Study Research Group, Persantine and aspirin in coronary heart disease, Circulation 62: 449 (1980).CrossRefGoogle Scholar
  7. 7.
    The Anturane Reinfarction Trial Research Group, Sulfinpyrazone in the prevention of cardiac death after myocardial infarction: The Anturane Reinfarction Trial, N. Engl. J. Med. 298: 289 (1978).CrossRefGoogle Scholar
  8. 8.
    The Anturane Reinfarction Trial Research Group, Sulfinpyrazone in the prevention of sudden death after myocardial infarc-tion, N. Engl. J. Med, 302: 250 (1980).CrossRefGoogle Scholar
  9. 9.
    W.S. Fields, N.A. Lemak, R.F. Frankowski and R.J. Hardy, Controlled trial of aspirin in cerebral ischemia, Stroke 8: 301 (1977).PubMedCrossRefGoogle Scholar
  10. 10.
    W.S. Fields, N.A. Lemak, R.F. Frankowski and R.J. Hardy, Controlled trial of aspirin in cerebral ischemia. Part II: Surgical group, Stroke 9: 309 ( 1978.PubMedCrossRefGoogle Scholar
  11. 11.
    Canadian Cooperative Study Group, A randomized trial of aspirin and sulfinpyrazone in threatened stroke, N. Engl. J. Med. 299: 53 (1978).CrossRefGoogle Scholar
  12. 12.
    J.W. Tukey, Some thoughts on clinical trials, especially problems of multiplicity, Science 198: 679 (1977).PubMedCrossRefGoogle Scholar
  13. 13.
    D.G. Kleinbaum and L.L. Kupper, “Applied regression analysis and other multivariable methods,” Wadsworth Publishing Company, Belmont, California (1978).Google Scholar
  14. 14.
    M. Gent, Recent intervention studies of platelet suppressant drugs in cerebral ischemia: Methodological aspects, in: “Drug Treatment and Prevention in Cerebrovascular Disorders,” G. Tognoni and S. Garattini, eds., Elsevier/North Holland Biomedical Press, Amsterdam (1979).Google Scholar
  15. 15.
    M. Gent and D.L. Sackett, The qualification and disqualification of patients and events in long-term cardiovascular clinical trials, Thromb. Hemostas. 41: 123 (1979).Google Scholar
  16. 16.
    D.L. Sackett and M. Gent, Controversy in counting and attributing events in clinical trials, N. Engl. J. Med. 301: 1410 (1979).PubMedCrossRefGoogle Scholar
  17. 17.
    M. Gent and J. Hirsh, Definition of high risk/high response population for stroke in patients with transient ischemic attacks, Thromb. Hemostas. 41: 40 (1979).Google Scholar
  18. 18.
    W.H. Harris, E.W. Salzman, C.A. Athanasoulis, A.C. Waltman and R.W. DeSanctis, Aspirin prophylaxis of venous thrombo-embolism after total hip replacement, N. Engl. J. Med. 297: 1246 (1977).PubMedCrossRefGoogle Scholar
  19. 19.
    A. Linos, J.W. Worthing, W. O’Fallon, V. Fuster, J.P. Whisnant and L.T. Kurland, Effect of aspirin on prevention of coronary and cerebrovascular disease in patients with rheumatoid arthritis. A long-term follow-up study, Mayo Clin. Proc. 53: 581 (1978).PubMedGoogle Scholar
  20. 20.
    J. Hirsh, M. Blajchman and A. Kaegi, The bleeding time, in: “Platelet Function Testing,” DHEW Publication No. (NIH) 78-1087, Washington (1978).Google Scholar
  21. 21.
    A. Kaegi, G.F. Pineo, A.G. Shimizu, H. Trivedi, J. Hirsh and M. Gent, The prevention of arteriovenous shunt thrombosis by sulfinpyrazone, N. Engl. J. Med. 290: 304 (1974).PubMedCrossRefGoogle Scholar
  22. 22.
    M. Johnson, E. Ramey and P.W. Ramwell, Sex and age difference in human platelet aggregation, Nature 253: 355 (1975).PubMedCrossRefGoogle Scholar
  23. 23.
    J.G. Kelton, J. Hirsh, C.J. Carter and M.J. Buchanan, Sex differences in the antithrombotic effects of aspirin, Blood 52: 1073 (1978).PubMedGoogle Scholar
  24. 24.
    G.J. Kelliher, R.K. Dix, M. Jurkiewicz and T.L. Lawrence, Effect of sulfinpyrazone on arrhythmia and death following coronary occlusion in cats, in: “Cardiovascular Actions of Sulfinpyrazone,” M. McGregor, J.F. Mustard, M. Oliver and S. Sherry, eds., Symposia Specialists Inc., Summit, New Jersey (1980).Google Scholar

Copyright information

© Springer Science+Business Media New York 1981

Authors and Affiliations

  • Michael Gent
    • 1
  1. 1.Faculty of Health SciencesMcMaster UniversityHamiltonCanada

Personalised recommendations