Breaking New Ground: Data Monitoring in the Coronary Drug Project

  • Paul L. Canner


Arriving at a decision for early termination of a treatment group or of an entire clinical trial, due to either beneficial or adverse results, is a complex process. It may involve, among other things, the need to (1) determine whether the observed treatment differences are likely to represent real effects and are not due to chance; (2) weigh the importance of different response variables, some possibly trending in favor of the treatment and some against it; (3) adjust for differences in distributions of baseline characteristics among the treatment groups; (4) discern possible biases (due to the study not being double-blind) in the medical management of patients or in the diagnosis of events; and (5) evaluate treatment effects in subgroups of the study participants. Experiences from the Coronary Drug Project in making decisions for early termination and for non-termination of treatment groups are described.


Data Monitoring Case Study Approach Coronary Heart Disease Death Coronary Drug Project Niacin Group 
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  1. 1.
    Zukel WJ. 1983. Evolution and funding of the Coronary Drug Project. Control Clin Trials 4:281–312.CrossRefGoogle Scholar
  2. 2.
    Coronary Drug Project Research Group. 1973. The Coronary Drug Project. Design, methods, and baseline results. Circulation 47(suppl. 1):I1–I79.Google Scholar
  3. 3.
    Canner PL, Klimt CR. 1983. Experimental design features of the Coronary Drug Project. Control Clin Trials 4:313–332.CrossRefGoogle Scholar
  4. 4.
    Dunnett CW. 1955. Multiple comparison procedures for comparing several treatments with a control. J Am Statist Assoc 50:1096–1121.zbMATHCrossRefGoogle Scholar
  5. 5.
    Canner PL. 1983. Monitoring of the data for evidence of adverse or beneficial treatment effects in the Coronary Drug Project. Control Clin Trials 4:467–483.CrossRefGoogle Scholar
  6. 6.
    Coronary Drug Project Research Group. 1970 The Coronary Drug Project. Initial findings leading to modifications of its research protocol. JAMA 214:1303–1313.CrossRefGoogle Scholar
  7. 7.
    Coronary Drug Project Research Group. 1972. The Coronary Drug Project. Findings leading to further modifications of its protocol with respect to dextrothyroxine. JAMA 220:996–1008.CrossRefGoogle Scholar
  8. 8.
    Coronary Drug Project Research Group. 1973. The Coronary Drug Project. Findings leading to discontinuation of the 2.5 mg/day estrogen group. JAMA 226:652–657.CrossRefGoogle Scholar
  9. 9.
    Coronary Drug Project Research Group. 1975. Clofibrate and niacin in coronary heart disease. JAMA 231:360–381.CrossRefGoogle Scholar
  10. 10.
    Coronary Drug Project Research Group. 1981. Practical aspects of decision making in clinical trials: The Coronary Drug Project as a case study. Control Clin Trials 1:363–376.CrossRefGoogle Scholar
  11. 11.
    Armitage P, McPherson CK, Rowe BC. 1969. Repeated significance tests on accumulating data. J R Statist Soc A 132:235–244.MathSciNetCrossRefGoogle Scholar
  12. 12.
    Canner PL. 1977. Monitoring treatment differences in long-term clinical trials. Biometrics 33:603–615.CrossRefGoogle Scholar
  13. 13.
    Miller RG. 1966. Simultaneous Statistical Inference. McGraw-Hill, New York.zbMATHGoogle Scholar
  14. 14.
    Halperin M, Ware J. 1974. Early decision in a censored Wilcoxon two-sample test for accumulating survival data. J Am Statist Assoc 69:414–422.MathSciNetzbMATHCrossRefGoogle Scholar
  15. 15.
    Armitage P. 1975. Sequential Medical Trials, 2nd ed. Wiley, New York.Google Scholar
  16. 16.
    Cornfield J. 1966. Sequential trials, sequential analysis and the likelihood principle. Am Statistician 20:18–23.zbMATHCrossRefGoogle Scholar
  17. 17.
    Cornfield J. 1966. A Bayesian test of some classical hypotheses—with applications to sequential clinical trials. J Am Statist Assoc 61:577–594.MathSciNetCrossRefGoogle Scholar
  18. 18.
    Cornfield J. 1969. The Bayesian outlook and its application. Biometrics 25:617–657.MathSciNetCrossRefGoogle Scholar
  19. 19.
    Feinstein AR. 1977. Clinical biostatistics. XLI. Hard science, soft data, and the challenges of choosing clinical variables in research. Clin Pharmacol Ther 22:485–498.Google Scholar
  20. 20.
    Coronary Drug Project Research Group. 1980. Influence of adherence to treatment and response of cholesterol on mortality in the Coronary Drug Project. N Engl J Med 303:1038–1041.CrossRefGoogle Scholar
  21. 21.
    Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W. 1986. Fifteen year mortality in Coronary Drug Project patients: Long-term benefit with niacin. J Am Coll Cardiol 8:1245–1255.CrossRefGoogle Scholar
  22. 22.
    Coronary Drug Project Research Group. 1976. Aspirin in coronary heart disease. J Chron Dis 29:625–642.CrossRefGoogle Scholar
  23. 23.
    Canner PL. 1984. Monitoring long-term clinical trials for beneficial and adverse treatment effects. Commun Statist Theor Meth 13:2369–2394.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Paul L. Canner
    • 1
  1. 1.Maryland Medical Research InstituteBaltimore

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