Pill Count Measures of Compliance in a Drug Trial: Variability and Suitability

Abstract

To evaluate pill counts as a compliance measure for drug trials, we followed 121 ambulatory hypertensives selected for good compliance over less than or equal to 12 months. The medication regimens consisted of either pinacidil or hydralazine as monotherapy or with propranolol and/or hydrochlorothiazide. Pill counts for the two primary drugs were obtained at each of the 20 return visits. The population was characterized by chronic uncomplicated hypertension and sociodemographic diversity; mean age was 53 years. Despite excellent average weekly pill counts (overall mean compliance rate [+/- SD] = 96.0 +/- 13.2%), we observed large intersubject and intrasubject variance in weekly pill count assessment: individuals' mean standard deviation = 13.7% (range = 0%-86%) and mean coefficient of variation = 0.138 (range = 0.001-0.410). By pill count, 35% of individuals exhibited greater than 110% compliance on at least 1 visit. We conclude that (a) pill count variability is large, even among highly selected subjects, (b) traditional reports of overall pill counts are suboptimal, and (c) pill counts may unreliably measure medication-taking behavior because "supranormal" compliance by this method is improbable but common.

Evaluation of Adherence Should Become an Integral Part of Assessment of Patients With Apparently Treatment-Resistant Hypertension

“…33 Indirect methods are simple, inexpensive, and time-efficient, and they imply a reasonable workload. 27,[34][35][36] On the other hand, the sensitivity of these methods is poor 35,[37][38][39][40] ; they are heavily dependent on patient behavior, 41,42 affected by social desirability and recall biases, [43][44][45][46][47] and fail to provide information about the timing of doses, which is an essential 48 Accordingly, they are poorly correlated with direct methods such as MEMS and drug dosage in body fluids. 35,37,42,44,45,47 In particular, in a sample of 47 patients with apparently resistant hypertension, poor adherence was grossly underestimated by the Morisky Medication Adherence Scale-8 (26%) compared with drug monitoring (51%).…”

Positive impact of compliance to strontium ranelate on the risk of nonvertebral osteoporotic fractures

“…The use of sophisticated techniques such as biologic assays is restricted to research. All these methods have shown their limitations [46][47][48].…”

Assessing Antiretroviral Adherence via Electronic Drug Monitoring and Self-Report: An Examination of Key Methodological Issues

“…A frequent refrain among reviewers of the medication adherence literature, dating back to the field's pioneers (Rudd et al, 1988), laments the difficulty in measuring adherence and underscores the need for further research and better methods. In addition to uncertainty about the best assessment strategy, there is little consensus regarding how best to operationalize medication adherence for analysis (Osterberg & Blaschke, 2005).…”