DOSE FREQUENCY AND DOSE INTERVAL COMPLIANCE WITH MULTIPLE ANTIEPILEPTIC MEDICATIONS DURING A CONTROLLED CLINICAL-TRIAL

Compliance with medication regimens and clinical trial schedules was e valuated during a study of vigabatrin (VGB), an antiepileptic drug (AE D). Medication Event Monitors (MEMS, Aprex Corp., Fremont, CA, U.S.A.) were provided to monitor use of VGB and other AEDs administered to 11 1 patients at 10 sites. MEMS reports showed the number of doses admini stered daily, times of doses, and intervals between doses. The 66 pati ents whose data were evaluable took VGB as prescribed (twice daily, b. i.d.) on 89 +/- 7% of days in the clinical trial (mean 189 +/- 63 days ). However, only 66 +/- 24% of doses were taken within the 9-15-h dose interval window for twice-daily dosing, a lower rate than that for do se frequency compliance (p < 0.001). Concomitant medications prescribe d b.i.d. (n = 66) (86 +/- 11% dose frequency compliance) were taken at lower rates than VGB (p < 0.02), Interval compliance also was lower f or concomitant b.i.d. medications (59 +/- 26%) than for VGB (p < 0.01) . Dose frequency compliance for thrice-daily (t.i.d.) medications (n = 36) was 80 +/- 18 and 40 +/- 19% for interval compliance (6-10 h) (bo th p < 0.0001 vs. VGB). Dose frequency compliance for four times daily (q.i.d.) medications (n = 23) was 80 +/- 23 and 33 +/- 18% for interv al compliance (4-8 hf (both p < 0.0001 vs. VGB). Patients at eight sit es did not use MEMS properly, often for practical reasons, voiding inc luding of data for 93 medications (32%) because of noncompliance with the study design to monitor compliance. Medication monitoring showed d ifferences in dose frequency compliance and dose interval compliance b etween investigational and concomitant medications, as well as study p rotocol noncompliance, by outpatients in a long-term clinical trial.