OUTCOMES OF A PLACEBO RUN-IN PERIOD IN A HEAD AND NECK-CANCER CHEMOPREVENTION TRIAL

This study describes the outcomes of an eight-week placebo run-in peri od in a head and neck cancer chemoprevention trial. Of 391 former canc er patients who entered the run-in over the first two years of the tri al, 91% were randomized. Pill counts showed that adherence rates range d from 0% to 120% (mean 96%, SD = 15%). The trial did not randomize su bjects who were no longer interested in trial participation (n = 20), who did not return within 10 weeks of enrollment date (n = 3), or who did not achieve a drug adherence level of at least 75% (n = 9). Three subjects were not randomized for other reasons. Univariate predictors of run-in outcome (randomized or not randomized) included ethnicity, e ducation level, cancer site, cancer stage, and Karnofsky performance s core. Multivariate analyses resulted in a logistic model with Karnofsk y performance and education level as significant predictors of randomi zation. Persons with a Karnofsky score of 100 had 2.3 higher odds of r andomization (95% CI = 1.1, 4.9) than persons with compromised Karnofs ky scores, and persons with more than a high school education had 2.1 higher odds of randomization (95% CI = 1.0, 4.9) than persons with les s education. These results suggest that the use of a run-in period may compromise the external validity of randomized prevention trials. Mor e research is needed to understand further the behavioral factors unde rlying the observed differences so that prevention researchers can dev elop effective interventions for facilitating trial participation, esp ecially in underrepresented, trial-eligible groups. Investigators shou ld expand the objectives of a run-in period to (1) evaluate why eligib le persons refuse trial enrollment or fail to be randomized at the end of the run-in and (2) use the run-in period for a systematic evaluati on of levels and costs of intervention strategies designed to promote trial enrollment and adherence. (C) Elsevier Science Inc. 1997.