NCT00414817.

Methods	Design: open‐label, pragmatic, parallel‐group randomised controlled trial Duration: 78 weeks Setting: conducted through 2 Kaiser Permanente research centres in Hawaii and Baltimore. USA Trial registration: NCT00414817
Participants	Population: 14,064 adults with asthma randomised to receive interactive voice response calls or usual care. Not all participants were previous ICS users. 3171 of the intervention group and 3260 of the usual care group described as the primary analysis sample ‐ previous ICS users Age: 18 years of age and older; ages reported in categories rather than as mean (SD) Baseline asthma severity: 33.3% had comorbid COPD; other characteristics included recent ED visit, hospitalisation or OCS burst for asthma; current SABA usage; and number of medications used Inclusion criteria: Target population consisted of KPNW and KPH members 18 years of age and older who were members for the 12 months before randomisation, had been seen for asthma and received at least 1 dispensing of a respiratory medication during that time frame. For study of both primary and secondary ICS adherence, target population included individuals without evidence of prior ICS use. Present analysis focuses on the subset of 6903 individuals with ICS dispensing during baseline year Exclusion criteria: Individuals meeting the above criteria were included in the final analysis sample only if they had ever received (or for usual care participants would have qualified for) an intervention call Percentage withdrawn: of 6903 previous users qualifying for analysis, 3171 were included in the intervention analysis sample and 3260 in the usual care analysis sample Other allowed medication: not reported
Interventions	Intervention summary: interactive voice recognition (IVR) intervention including 3 basic IVR call types, each typically lasting 2 to 3 minutes: refill reminder call, for people whose last ICS dispensing was at least a month ago and who should have < 30 days supply left, reminded participants that they were due for a refill and offered a transfer to the automated pharmacy refill line and/or information about KP’s online refill service; tardy refill call, for people > 1 month past refill date, reminded participants they were due for an ICS refill, assessed asthma control, explored ICS adherence barriers and provided tailored educational messages; and initiator/restart call, for participants who were starting ICS for the first time or were lapsed users, included probes for asthma control and adherence barriers and offered tailored educational messages Control summary: usual care Complex intervention: no
Outcomes	Outcomes measured: 8 alternative measures of pharmacy‐based adherence, described as continuous multiple‐interval measures of medication availability and gaps. Clinicaltrials.gov lists the primary outcome as days' supply of ICS available as documented in participants' pharmacy records at 19 months, and secondary outcomes as health status from survey responses (subset), utilisation of acute healthcare services from medical record data and an economic analysis. Multiple post hoc analyses provided in published reports Adherence calculation: 8 alternative measures of pharmacy‐based adherence (one of the resulting publications is a comparison of pharmacy‐based measures of medication adherence)
Notes	Type of publication: multiple peer‐reviewed journal articles Funding: NHLBI
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Randomization stratified by region and the clinic facility to which each patient was paneled" ‐ but no further details about how the random sequence was generated
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	Although it was not possible to blind participants to group allocation, the primary outcome (adherence) was measured objectively using pharmacy data. However, as participants would have been aware that they were taking part in a trial of adherence and were being monitored, this may have affected their adherence behaviour beyond the effect intended by the intervention
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of outcome assessors is not described; however, the nature of the primary outcomes (adherence measured using pharmacy data) makes them not prone to detection bias
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Owing to the trial design, it was not possible to measure attrition in the usual way
Selective reporting (reporting bias)	High risk	Prospectively registered trial (NCT00414817), but many outcomes of interest not presented numerically, so unable to include it in the meta‐analysis ("We also observed no significant intervention effects on reliever medication (SABA) use, quality of life, asthma control, or the rate of acute asthma health care utilization")
Other bias	Low risk	None noted