In 2010 the ‘Polymedication Check’ (PMC), a pharmacist-led medication review, was newly introduced to be delivered independently from the prescriber and reimbursed by the Swiss health insurances. This study aimed at evaluating the impact of this new cognitive service focusing on medicines use and patients’ adherence in everyday life. This randomised controlled trial was conducted in 54 Swiss community pharmacies. Eligible patients used ≥4 prescribed medicines over >3 months. The intervention group received a PMC at study start (T-0) and after 28 weeks (T-28) while the control group received only a PMC at T-28. Primary outcome measure was change in patients’ objective adherence, calculated as Medication Possession Ratio (MPR) and Daily Polypharmacy Possession Ratio (DPPR), using refill data from the pharmacies and patient information of dosing. Subjective adherence was assessed as secondary outcome by self-report questionnaires (at T-0 and T-28) and telephone interviews (at T-2 and T-16), where participants estimated their overall adherence on a scale from 0–100 %. A total of 450 patients were randomly allocated to intervention (N = 218, 48.4 %) and control group (N = 232, 51.6 %). Dropout rate was fairly low and comparable for both groups (N Int = 37 (17.0 %), NCont = 41 (17.7 %), p = 0.845). Main addressed drug-related problem (DRP) during PMC at T-0 was insufficient adherence to at least one medicine (N = 69, 26.7 %). At T-28, 1020 chronic therapies fulfilled inclusion criteria for MPR calculation, representing 293 of 372 patients (78.8 %). Mean MPR and adherence to polypharmacy (DPPR) for both groups were equally high (MPRInt = 88.3, SD = 19.03; MPRCont = 87.5, SD = 20.75 (p = 0.811) and DPPRInt = 88.0, SD = 13.31; DPPRCont = 87.5, SD = 20.75 (p = 0.906), respectively). Mean absolute change of subjective adherence between T-0 and T-2 was +1.03 % in the intervention and −0.41 % in the control group (p = 0.058). The number of patients reporting a change of their adherence of more than ±5 points on a scale 0–100 % between T-0 and T-2 was significantly higher in the intervention group (NImprovement = 30; NWorsening = 14) than in the control group (NImprovement = 20; NWorsening = 24; p = 0.028). Through the PMC pharmacist were able to identify a significant number of DRPs. Participants showed high baseline objective adherence of 87.5 %, providing little potential for improvement. Hence, no significant increase of objective adherence was observed. However, regarding changes in subjective adherence of more than ±5 % the PMC showed a positive effect. Clinical trial registry database, NCT01739816 ; first entry on November 27, 2012.

Introduction Despite much research, interventions to improve medication adherence report disappointing and inconsistent results. Tailored approaches that match interventions and patient determinants of non-adherence were seldom used in clinical trials. The presence of a multitude of theoretical frameworks and models to categorize interventions and patient determinants complicated the development of common categories shared by interventions and determinants. We retrieved potential interventions and patient determinants from published literature on medication adherence, matched them like locks and keys, and categorized them according to the Theoretical Domains Framework (TDF). Methods We identified the most relevant literature reviews on interventions and determinants in a pragmatic literature search, extracted all interventions and determinants, grouped similar concepts to umbrella terms and assigned them to TDF categories. All steps were finalized in consensus discussion between the authors. Results Sixteen articles (5 with determinants, 11 with interventions) were included for analysis. We extracted 103 interventions and 42 determinants that we divided in 26 modifiable and 16 unmodifiable determinants. All interventions and modifiable determinants were matched within 11 categories (Knowledge; Skills; Social/professional role and identity; Beliefs about capabilities; Beliefs about consequences; Intentions; Memory, Attention and decision processes; Environmental context and resources; Social influences; Emotion; and Behavioral regulation). Conclusion In published trials on medication adherence, the congruence between interventions and determinants can be assessed with matching interventions to determinants. To be successful, interventions in medication adherence should target current modifiable determinants and be tailored to the unmodifiable determinants. Modifiable and unmodifiable determinants need to be assessed at inclusion of intervention studies to identify the patients most in need of an adherence intervention. Our matched categories may be useful to develop interventions in trials that investigate the effectiveness of adherence interventions.

This was a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Evidence mapping was used to reveal the effect of drug reminder packaging on medication adherence, to identify research gaps and to make suggestions for future research.