Planning the Size of Clinical Trials with Allowance for Patient Noncompliance^[*]

Abstract

Various approaches are considered for adjustment of clinical trial size for patient noncompliance. Such approaches either model the effect of noncompliance through comparison of two survival distributions or two simple proportions. Models that allow for variation of noncompliance and event rates between time intervals are also considered. The approach that models the noncompliance adjustment on the basis of survival functions is conservative and hence requires larger sample size. The model to be selected for noncompliance adjustment depends upon available estimates of noncompliance and event rate patterns.

Key-Words

Clinical Trial - Sample Size - Noncompliance - Survival Analysis - Proportions

^* This work was presented in part at the International Statistical Institute, 1989, Paris, France.

• REFERENCES

• 1 Lachin JM, Foulkes MA. Evaluation of sample size and power for analyses of survival with allowance for nonuniform patient entry, losses to follow-up, noncompliance and stratification. Biometrics 1986; 42: 507-19.
• 2 Gross AJ, Clark VA. Survival Distributions: Reliability Applications in the Biomedical Sciences. New York: Wiley; 1975
• 3 Rubinstein LV, Gail MH, Santner TJ. Planning the duration of a comparative clinical trial with loss to follow-up and a period of continued observation. J Chronic Diseases 1981; 34: 469-79.
• 4 Schoenfeld DA, Richter JR. Nomograms for calculating the number of patients needed for a clinical trial with survival as an endpoint. Biometrics 1982; 38: 163-70.
• 5 Lachin JM. Introduction to sample size determination and power analysis for clinical trials. Controlled Clin Trials 1981; 02: 93-113.
• 6 George SL, Desu MM. Planning the size and duration of a clinical trial studying the time to some critical event. J Chron Dis 1974; 27: 15-24.
• 7 Fleiss JL. Statistical Methods for Rates and Proportions. New York: Wiley; 1981
• 8 Schork MA, Remington RD. The determination of sample size in treatment-control comparisons for chronic disease studies in which dropout or nonadherence is a problem. J Chron Dis 1967; 20: 233-8.
• 9 Halperin M, Rogot E, Gurian J, Ederer F. Sample sizes for medical trials with special reference to long-term therapy. J Chron Dis 1968; 21: 13-24.
• 10 Wu M, Fisher M, DeMets D. Sample sizes for long-term medical trial with time-dependent dropout and event rates. Controlled Clin Trials 1980; 1: 109-21.
• 11 Donner A. Approaches to sample size estimation in the design of clinical trials -A review. Statist in Med 1984; 03: 199-214.