Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals

Abstract

Background: Compliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed.

Methods: We determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel.

Results: Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports.

Conclusions: Compliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic in silico simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.

Figure 1

Daily compliance during study observation period for each month and the entire observation period. The ends of the whiskers represent the lowest data value within 1.5 times the box height from the lower box edge and the highest data value within 1.5 times the box height from the upper box edge, respectively. Index numbers represent individual patients ID: if associated with circle, this ID was regarded as outlier (1.5-3 times box height from the box edge), if with a star as extreme value (> 3 times box height from the box edge); mo. = month.

Figure 2

Intraindividual daily compliance during the observation period. Compliant months (daily compliance ≥ 80%, white bars) or non-compliant months (daily compliance < 80%, grey bars); patient #11 and patient #31 participated five months only.

Figure 3

Forgiveness characterisation: Simulation approach B. Time with therapeutic undersupply (TTU) in percentage of total time versus discrete daily compliance values.

Figure 4

Forgiveness characterisation: Simulation approach C. Total time with therapeutic undersupply (TTU) in hours versus number of dosage omissions at steady-state.