Evaluation of Some Strategies for Treating Concomitant Factors in Randomized Trials

Summary

In a randomized clinical trial, the design may or may not be stratified, the analysis may or may not be adjusted. The cross-classification of these alternatives leads to four different strategies. These strategies, plus another one, are evaluated within the framework of a linear model. A discussion about the conditional and unconditional points of view throws some light on the problem of bias in a randomized trial.

In einer randomisierten klinischen Studie kann die Versuchsanlage stratifiziert sein oder nicht, die Analyse bereinigt oder nicht. Die Kreuzklassifikation dieser Alternativen führt zu vier verschiedenen Strategien. Diese Strategien sowie eine weitere werden im Rahmen eines linearen Modells bewertet. Eine Diskussion der konditionalen und nicht-konditionalen Gesichtspunkte beleuchtet das Problem des Bias bei einer randomisierten Studie.

Key-Words

Randomized Trial - Concomitant Factors - Stratification

Schlüssel-Wörter

Randomisierte Studie - Begleitfaktoren - Stratifizierung

• REFERENCES

• 1 Armitage P. The analysis of data from clinical trials. Statistician 1979; 28: 171-183.
• 2 Brown Jr. B. W. Statistical controversies in the design of clinical trials. Some personal views. Contr. clin. Trials 1980; 1: 13-27.
• 3 Chalmers T. C, Celano P, Sacks H. S, Smith H. Bias in treatment assignment in controlled clinical trials. New Engl. J. Med 1983; 309: 1358-1361.
• 4 Cox D. R. The use of a concomitant variable in selecting an experimental design. Biometrika 1957; 44: 150-158.
• 5 Cox D. R. Randomization and concomitant variables in the design of experiments. In Kallianpur G, Krishnaiah P. R, Ghosh J. K. (Eds.) Statistics and Probability: Essays in Honor of C. R. Rao. Amsterdam: North-Holland Publ. Co; 1982: 197-202.
• 6 Fisher R. A. The Design of Experiments. Edinburgh: Oliver and Boyd; 1935
• 7 Green S. B, Byar D. P. The effect of stratified randomization on size and power of statistical tests in clinical trials. J. chron. Dis 1978; 31: 445-454.
• 8 Kempthorne O. The randomization theory of experimental inference. J. Amer. stat. Ass 1955; 50: 946-967.
• 9 Kendall M. G, Stuart A. The Advanced Theory of Statistics, Vol.2. London: Griffin; 1977
• 10 Lavori P. W, Louis T. A, Bailar J. C, Polansky M. Designs for experiments. Parallel comparisons of treatment. New Engl. J. Med 1983; 309: 1291-1298.
• 11 McHugh R, Matts J. Post-stratification in the randomized clinical trial. Biometrics 1983; 39: 217-225.
• 12 Meier P. Stratification in the design of a clinical trial. Contr. clin. Trials 1981; 1: 355-361.
• 13 Peto R, Pike M. C, Armitage P, Breslow N. E, Cox D. R, Howard S. V, Mantel N, McPherson K, Peto J, Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. Brit. J. Cancer 1976; 34: 585-612.
• 14 Pocock S. J. Allocation of patients to treatment in clinical trials. Biometrics 1979; 35: 183-197.
• 15 Pocock S. J, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 1975; 31: 103-115.
• 16 Simon R. Restricted randomization designs in clinical trials. Biometrics 1979; 35: 503-512.
• 17 University Group Diabetes Program. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes: I. Design, methods and baseline results. II. Mortality results. Diabetes 1970; 19 Suppl (Suppl. 02) 747-788.
• 18 Zelen M. The randomization and stratification of patients to clinical trials. J. chron. Dis 1974; 27: 365-375.