Vollmer 2014.

Study characteristics
Methods	Randomised controlled clinical trial (RCT) Randomisation ratio: 1:1:1 Equivalence design: (2‐sided confidence interval) Open label
Participants	N recruited = 45,051 N randomised = 21,752 (7255 control, 7247 IVR, 7250 IVR+) for all, 16,380 for statins, and 13,063 for ACEi/ARB N reported outcomes: Statin adherence = 16,366 and LDL levels = 13,776 Mean age 63.6 yrs (SD 12.2), 53% men INCLUSION CRITERIA ≥ 40 years old (Mean age 63.6) “Using each region’s EMR, we identified participants 40 years and older with diabetes mellitus and/or cardiovascular disease (CVD), suboptimally (<90%) adherent to a statin or ACEI/ARB during the previous 12 months, and due or overdue for a refill” EXCLUSION CRITERIA “We excluded only individuals with medical conditions that might contraindicate the use of these medications, such as medication allergies, liver failure, cirrhosis, rhabdomyolysis, end‐stage renal disease, chronic kidney disease and those on KP’s “do not contact” list.” COUNTRY/SETTING: 3 regions of the Kaiser Permanente (KP) health plan—Northwest (KPNW), Hawaii (KPH), and Georgia (KPG), USA STUDY PERIOD: "Study enrollment began in December 2011 and continued through May 2012. Intervention and outcome assessment continued through November 2012."
Interventions	Number of study centres: 3 regions of the Kaiser Permanente (KP) health plan—Northwest (KPNW), Hawaii (KPH), and Georgia (KPG) CONTROL GROUP “UC participants had access to the full range of usual services, including each region’s normal education and care management outreach efforts to encourage statin and ACEI/ARB use.” INTERVENTION GROUPS Interactive Voice Recognition (IVR) Calls “VR participants received automated phone calls when they were due or overdue for a refill. The calls used speech‐recognition technology to educate patients about their medications and help them refill prescriptions (we created separate “refill” and “tardy” calls). The flow of each call was determined by participants’ responses; each call lasted 2 to 3 minutes. At randomization, IVR participants received a pamphlet explaining these calls. Both call types offered a transfer to KP’s automated pharmacy refill line. The tardy call also offered a transfer to a live pharmacist. With permission, obtained at the first successful call contact, the program left detailed messages on answering machines or with another household member.” Enhanced IVR (IVR+) “In addition to IVR calls, participants in the IVR+ arm received a personalized re‐minder letter if they were 60 to 89 days overdue and a live outreach call if they were ≥90 days overdue, as well as EMR‐based feedback to their primary care provider. IVR+ participants received additional materials, including a personalized health report with their latest BP and cholesterol levels, a pill organizer, and bimonthly mailings.”
Outcomes	“We used a modified version of the Proportion of Days Covered (PDC),16 defined from pharmacy dispensing records, for our primary measure. Because we were measuring adherence to chronic medications patients were known to be taking at randomization, we modified the PDC (mPDC) to include the whole follow‐ up period as the denominator time frame rather than time from first dispensing.17 We accounted for medication on hand at randomization and ignored any medication remaining at the end of follow‐up. We computed mPDCs separately for statins and ACEI/ARBs.” PRIMARY OUTCOMES: medication adherence SECONDARY OUTCOMES: lipid Levels, blood pressure
Notes	Commercial funding/non‐commercial funding/other funding: “This project was supported by grant number R01HS019341 from the Agency for Healthcare Research and Quality.” Stated aim for study: “Evaluate the utility of 2 electronic medical record (EMR)‐linked, automated phone reminder interventions for improving adherence to cardiovascular disease medications.”
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Computer‐generated randomization assignments were stratified by region and blocked to assure balance across treatment arms"
Allocation concealment (selection bias)	Low 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	16,380 randomised for statins with adherence data for 16,366 at end of study
Selective reporting (reporting bias)	Low risk	All outcomes reported