The natural history of medication compliance in a drug trial: Limitations of pill counts

To assess medication compliance over time, we prospectively performed pill counts among 121 ambulatory hypertensive subjects for ⩽ 12 months. Prescribed regimens consisted of pinacidil or hydralazine administered four times a day and of secondary drugs administered up to twice daily. Surreptitious pill counts occurred every 1 to 12 weeks. Among a middle‐aged subject group that had been selected for high rates of compliance, we observed mean compliance rates that approximated 100%. We noted marked intrasubject and intersubject variability for any one medication, between medications, and over time. From baseline blood pressures (±SE) of 155.5 ± 1.9/97.3 ± 1.0 mm Hg, subsequent mean blood pressures varied by compliance subgroup: “hypocompliers” (< 80%), 151.3/91.0 mm Hg; “hypercompliers” (⩾ 120%), 147.6/91.4 mm Hg; and “eucompliers” (80% to 119%), 143.3/88.5 mm Hg (systolic blood pressure: F 1,52 = −220.9, NS; diastolic blood pressure: F 1,52 = −121.4, NS). We concluded that weekly pill counts indicated marked intersubject and intrasubject variability, obscured by long‐term averages; that compliance lapses appeared to be random; and that excessive medication‐taking was the most consistent with “pill dumping.” Clinical Pharmacology and Therapeutics (1989) 46 , 169–176; doi: 10.1038/clpt.1989.122