Improved compliance measures: applications in an ambulatory hypertensive drug trial.

To assess the value of improved monitoring of medication-taking behavior in a drug trial, we employed a modified pill vial with microcircuitry to record the precise times when the vials were opened. After a 3-week placebo washout period, 21 ambulatory subjects with mild hypertension (mean age, 57 years; 67% men; 76% white) randomly received isradipine or enalapril twice daily in a double-blind titration during 10 weeks. Both drugs achieved a 13% reduction in sitting diastolic blood pressure (p less than 0.01) with minimal symptomatic or laboratory toxicity. Although pill counts indicated near-perfect compliance (92% to 99% for both groups), the electronic monitor showed that fewer than half of all openings occurred at the prescribed interval of 12 +/- 2 hours. Modest overdispensing was documented in the 3 days before scheduled visits. The monitor confirmed that pill count misclassified compliance sufficiency in 22% of visits and permitted more discrete attribution for drug-associated adverse reactions and secondary resistance to treatment. We conclude that the electronic monitor reduces ambiguity about medication compliance and helps interpret both the biology and pharmacology of the trial.

RCT Entities:   Population Interventions Outcomes