Rickles 2005.

Methods	Randomization involved the researcher preparing 10 pieces of paper with sequential numbers for each participating pharmacist at the site. Each of the 8 pharmacies had a different cluster of numbers. When a patient was enrolled from a site, the researcher would randomly select a number out of the envelope. Selection of an odd or even number meant the patient was assigned to the control group or the intervention group, respectively. A total of 63 patients were randomized to either the intervention group (n = 31) or the control group (n = 32)
Participants	Patients were 18 years of age or older, willing to pick up their medication from a study pharmacy during the next 4 months, having no hearing impairment, having no antidepressant use in the last 4 months and planning to be in the local area in the next 4 months. Patients excluded from the study were those with a Beck Depression Inventory Second Edition (BDI‐II) score below 16, requiring a translator, pregnant or nursing, receiving medications for a psychotic or bipolar disorder, and/or having physical conditions requiring additional caution with their antidepressant
Interventions	Patients in the intervention group received 3 monthly calls from the pharmacists providing pharmacist‐guided education and monitoring (PGEM). On average, the first telephone call took place within the first 3 weeks of the patient picking up their initial antidepressant prescription from the pharmacy and took ˜19 minutes to complete. During the first call, the pharmacist assessed the patient's antidepressant knowledge and beliefs and clarified or explained issues that were not understood by the patients. Pharmacists rated the severity of their concerns and made suggestions on how to handle adverse effects, difficulties remembering or paying for medications, and other concerns. Also, the pharmacists accessed the patient's treatment goals or areas in which they hoped the medication would help, and how the medication was being used during the week before the telephone call. Pharmacists were expected to follow‐up on any indication of medication non‐adherence, inquire on why the doses were missed and make recommendations to increase medication compliance. The second and third telephone calls took place approximately 1 and 2 months after the initial call and on average, required 12 and 11 minutes to complete. During these calls, study pharmacists used the monitoring tool to guide their follow‐up on any concerns identified in earlier calls and made new recommendations as needed. Pharmacists reviewed current adherence, whether any new adverse effects or concerns had developed, and evaluated the patient's progress in their medication goals. Patients in the control group received 3 monthly calls from the pharmacists providing usual pharmacist's care ‐ defined as that education and monitoring which pharmacists may typically provide patients at the study pharmacies
Outcomes	Medication adherence was recorded after the first 3 months after enrollment and again after another 3 months. The number of missed doses was calculated by multiplying the number of prescribed doses per day times the number of days late between refills for the first 3‐month period and second 3‐month period. Results were multiplied by 100 to yield the percentage of missed doses for each period. The pharmacy records used for this method of compliance measurement were validated in 2 ways. First, the pharmacy records were compared with prescription insurance claims for 49 of 63 patients for whom claims data were available from the participating managed care organization. Inconsistencies were resolved by the research pharmacist after case‐by‐case analysis. Second, the patient's self reported antidepressant adherence was measured as part of the outcomes survey, "In the past 7 days ending yesterday, how many times did you miss taking a pill?" The BDI‐II was used to measure depression symptoms
Notes	While pharmacist‐guided education and monitoring had no significant impact on adherence at 3 months, a per‐protocol analysis revealed significantly improved adherence at 6 months for those who completed the study. When the 3 patients who withdrew from the study were included in the analysis, the difference did not reach significance at the 0.05 level
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization involved the researcher preparing 10 pieces of paper with sequential numbers for each participating pharmacist at the site. Each of the 8 pharmacies had a different cluster of numbers; the first site had numbers beginning with 100, the second site had numbers with 200, and so forth. Since the first site had 3 participating study pharmacists, 30 slips of paper numbered from 100 to 130 were prepared and placed into an envelope. When a patient was enrolled from that site, the researcher would randomly select a number out of the envelope. Selection of an odd or even number meant the patient was assigned to the usual care or PGEM group, respectively (pg 346)
Allocation concealment (selection bias)	Unclear risk	The study does not specify sequentially numbered, opaque, sealed envelopes. "Researcher: — Contacts patient to confirm eligibility and answers questions — Notifies pharmacist of eligible patients randomized to pharmacist‐guided education and monitoring." (pg 347)
Selective reporting (reporting bias)	Unclear risk	No protocol available; although it appears that everything was reported it is difficult to determine this without a protocol
Other bias	Unclear risk	States that a "...fifth study limitation pertains to randomization procedures. Since we randomized by patient and not by site, patients in the usual care group may have been exposed to improved antidepressant education and monitoring when they returned for refills. Thus, it is possible that the usual care group received enhanced care by study pharmacists." "Indeed, the invitation to participate in this study may have biased results in several ways due to the Hawthorne effect. Both study groups may have reported greater clinical improvement since they wanted to meet the expectations of interested pharmacists (especially since patients were unblinded to group assignment). This phenomenon may explain why study groups had greater antidepressant adherence than has been reported in the literature" (pg 352)
Blinding of outcome assessment (detection bias) Adherence measure	High risk	(PRIMARY) PHARMACY RECORD ‐ The author noted that the researcher was not blinded to study group
Blinding of outcome assessment (detection bias) Patient outcome	Unclear risk	(PRIMARY) DEPRESSION SYMPTOMS ‐ BDI‐II ‐ Procedures are unclear as to how the BDI‐II was returned to researchers
Blinding of participants (performance bias) Adherence measure	High risk	(PRIMARY) PHARMACY RECORD ‐ The author noted that the participants were not blinded to study group
Blinding of participants (performance bias) Patient outcome	High risk	(PRIMARY) DEPRESSION SYMPTOMS ‐ BDI‐II ‐ intent of BDI‐II would be obvious to patients. Any blinding could have been broken
Blinding of personnel (performance bias) Adherence measure	High risk	(PRIMARY) PHARMACY RECORD ‐ The author noted that the researcher was not blinded to study group
Blinding of personnel (performance bias) Patient outcome	Unclear risk	(PRIMARY) DEPRESSION SYMPTOMS ‐ BDI‐II ‐ Procedures are unclear as to how the BDI‐II was returned to researchers
Incomplete outcome data (attrition bias) Adherence measure	High risk	(PRIMARY) PHARMACY RECORD ‐ inclusion of the 3 dropouts reversed the results: "...we performed an intention‐to‐treat analysis that includes the three patient dropouts, this 6‐month difference was not significant (data not shown)."
Incomplete outcome data (attrition bias) Patient outcome	Unclear risk	(PRIMARY) DEPRESSION SYMPTOMS ‐ BDI‐II ‐ ITT analysis reversed results to not significant improvement in case of at least 1 outcome measure ‐ adherence. It is not known whether the incomplete data had any effect in the case of depression scores. (See table 2, pg 351)