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 period in a head and neck cancer chemoprevention trial. Of 391 former cancer patients who entered the run-in over the first two years of the trial, 91% were randomized. Pill counts showed that adherence rates ranged from 0% to 120% (mean 96%, SD = 15%). The trial did not randomize subjects 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, education level, cancer site, cancer stage, and Karnofsky performance score. Multivariate analyses resulted in a logistic model with Karnofsky performance and education level as significant predictors of randomization. Persons with a Karnofsky score of 100 had 2.3 higher odds of randomization (95% CI = 1.1, 4.9) than persons with compromised Karnofsky 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 less education. These results suggest that the use of a run-in period may compromise the external validity of randomized prevention trials. More research is needed to understand further the behavioral factors underlying the observed differences so that prevention researchers can develop effective interventions for facilitating trial participation, especially in under-represented, trial-eligible groups. Investigators should expand the objectives of a run-in period to (1) evaluate why eligible 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 evaluation of levels and costs of intervention strategies designed to promote trial enrollment and adherence.