Objective: The objective of this study was to demonstrate the utility of continuous monitoring and enhancement of medication compliance during a long-term clinical trial, predictors of compliance, and relationships to drinking outcomes.
Methods: Alcohol-dependent patients enrolled in a multicenter VA cooperative study were randomly assigned to once-daily naltrexone (NTX) for 3 or 12 months (short-term or long-term NTX) or placebo for 12 months of treatment. All medications were dispensed in bottles with medication event monitoring (MEMS, AARDEX, Union City, CA) caps with a microprocessor that recorded openings as presumptive doses. Patients were trained to develop personal cues as dosing reminders. Monthly feedback sessions included review of compliance data and cues.
Results: There were no significant differences among short-term NTX, long-term NTX, and placebo (209 each) groups in measures of compliance. Overall compliance rates were 71% +/- 31% of doses for the first 13 weeks and 43% +/- 33% of doses over 52 weeks. Some doses were taken during 83% +/- 27% of the first 13 weeks. Higher medication compliance predicted fewer drinks per drinking day (P = .02) throughout follow-up and a lower percentage of drinking days (P = .002 during the first 13 weeks) with no significant effect for treatment group.
Conclusions: The feedback and monitoring programs were important features to demonstrate that lack of treatment effect was not a result of poor compliance. Medication compliance data supported the internal validity of the trial by demonstrating that good compliers had better outcomes, irrespective of treatment with NTX or placebo. The MEMS feedback methodology is feasible for use in multicenter trials.