Vrijens 2006.

Study characteristics
Methods	Parallel cluster‐randomised controlled clinical trial Randomisation ratio: 1:1 Equivalence design: (2‐sided confidence interval) Open‐label
Participants	N recruited = 429 N randomised = 392 (198 control, 194 intervention) N reported outcomes = 392 Mean age 61.9 yrs (SD 9.9) in the intervention group and 60.4 yrs (SD 10.2) in the control group 55% men in the intervention group and 46% in the control group INCLUSION CRITERIA “All patients, aged 18 years or above, who had been taking atorvastatin for at least 3 months, and who had no contraindications to continuation of the treatment, could be included in the study provided they usually got their medication in one of the pharmacies participating in the study.“ EXCLUSION CRITERIA None reported COUNTRY/SETTING: Belgium STUDY PERIOD: Patients enrolled between 13 February 2000 and 26 June 2002
Interventions	Number of study centres: 35 pharmacies “In each linguistic region, one district was randomized to deliver care as usual (control group), while in the other district a patient intervention through a pharmaceutical care program was implemented (intervention group).” “The supportive intervention program consisted of review by the patients’ pharmacist, jointly with the patient, of the electronically compiled dosing history, a ‘beep‐card’ that reminds patient of the dosing time, and educational reminders. In the intervention group, the pharmacist delivered an educational message at each follow‐up visit, updated the ‘compliance passport’ and analyzed, together with the patient, the electronically compiled dosing history of the past month/ 3 months.”
Outcomes	“The primary outcome parameter is ‘post‐baseline adherence’ to prescribed therapy defined for each patient as the proportion of days during which the MEMS record showed that the patient had opened the pill container. The estimation of this variable started from the second pharmacy visit until an arbitrary cut‐off point of 300 days after inclusion. ‘Baseline adherence’ is estimated between inclusion and the second visit to the pharmacy. Adherence can vary in many different ways over time. Summarizing the history in just one measure may hide important features of adherence patterns, especially potential changes over time. We captured the temporal evolution of daily adherence to study this clinically relevant aspect of dosing history data. Further we found it useful to define persistence as the length of time between onset and discontinuation of treatment execution.” PRIMARY OUTCOMES: adherence, persistence
Notes	Publication details Commercial funding/non‐commercial funding/other funding: “No conflict of interest was declared. Contract grant sponsor: Pfizer Belgium, Boulevard de la Plaine 17, BE 1050 Bruxelles—Ixelles, Belgium.” Stated aim for study “The objective of this study was to estimate the effect of a pharmaceutical care program on the adherence of once‐daily atorvastatin treatment in patients with elevated cholesterol levels.”
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	“In each linguistic region, one district was randomized to deliver care as usual (control group), while in the other district a patient intervention through a pharmaceutical care program was implemented (intervention group)” “While we realize that there might be bias in the selection of the participating patients resulting three of the nine baseline variables being statistically significantly different between the two groups, the intervention effect remained significant in a multiple Cox regression analysis controlling for the baseline variables”
Allocation concealment (selection bias)	Unclear risk	See above
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Unblinded "open‐label study"
Incomplete outcome data (attrition bias) All outcomes	Low risk	“Between 13 February 2000 and 26 June 2002, 429 subjects were entered into the study, of whom 37 did not visit the pharmacy: hence, a total of 392 subjects are included in the ITT set, of whom 194 attended pharmacies that employed adherence enhancing interventions and 198 subjects had no intervention”
Selective reporting (reporting bias)	Low risk	All outcomes reported