Adherence to polypharmacy from a pharmaceutical care perspective : evalution of an electronic medication dispenser and of tailored adherence interventions in primary care

Modern medicine offers a multitude of evidence-based treatments for many chronic diseases. Polypharmacy, the prescription of multiple medications to treat one or more conditions in the same patient, has become increasingly common. Non-adherence to medication may be the principal reason for gaps between efficacy and effectiveness of treatments. Medication adherence is not a stable personality trait but a complex behavior influenced by discrete factors. Pharmacists as suppliers of medications with frequent patient contact are in a unique position to interview patients about barriers to treatment and to offer individual support to enhance their adherence. The management of polypharmacy and medication adherence represent important aspects of pharmaceutical care (PhC). Interventions to improve adherence are diverse, often complex, and show inconsistent results. Research about interventions addressing barriers associated with polypharmacy is scarce. Medication management aids (MMA) are widely used tools to overcome challenges with complex regimens. Apart from the visual cue to take their medication, more advanced electronic MMAs (e-MMAs) may offer more explicit reminders, such as visual or audible alerts. Electronic monitoring can be used to provide customized feedback. Various e-MMAs for polypharmacy exist, but only few studies using these devices have been published.
The goal of this thesis was to investigate adherence to polypharmacy from a pharmaceutical care perspective.
PROJECT A aimed to review existing definitions of PhC and to describe the process of developing a redefined definition. A literature search identified 19 definitions that were paraphrased using a standardized syntax. Twenty-four experts defined PhC during a moderated workshop as “the pharmacist’s contribution to the care of individuals in order to optimize medicines use and improve health outcomes.”
PROJECT B aimed to analyze the prescription patterns of split tablets in general and of quetiapine in particular. Out of 4,784,999 tablets that were repacked in 2012 in unit-of-use pouch blisters for 1,321 patients residing in 53 retirement homes in northwestern Switzerland, 8.5% were fragmented. The patients were on average 81.5 years old and obtained 1.7 fragments. A total of 43.7% of patients received two or more fragments. The fragments concerned 132 different active substances, and 50% of them were psycholeptics or psychoanaleptics. Prescription of half quetiapine tablets appeared to be constricted to the region of Basel.
For PROJECT C, we investigated an e-MMA for pharmacy-filled blister pouches. PROJECT C1 aimed to collect opinions on MMAs in general and on the abovementioned e-MMA in particular. Six participants completed the 14-day trial and participated in a focus group. Participants rated ten of 17 general attributes as clearly applicable to the e-MMA and five as unsuitable. Attributes pertained to three interrelated themes: product design, patient support, and living conditions. Envisaged target groups were patients with time-sensitive medication regimens, patients with dementia, the visually impaired, and several patients living together to prevent accidental intake of the wrong medication.
In PROJECTS C2 – C5, we evaluated the e-MMA in older patients with opioid-assisted treatment (OAT), who often suffer from chronic diseases and disability in addition to their opioid dependence. As a result, they often need to deal with polypharmacy and complex regimens and are at high risk for medication non-adherence.
PROJECT C2 confirmed the increasing age and use of polypharmacy for opioid-dependent patients from an Outpatient Addiction Service (OAS) in Basel, Switzerland. In PROJECT C3, we report the first long-term experiences with a novel supply model with the e-MMA for two opioid-dependent patients with HIV. During the entire observation period of 1.7 and 2.6 years, respectively, both patients retrieved over 90% of the pouches within 75 minutes of the scheduled time. Viral loads fell below detection limits during the entire observation period.
PROJECT C4 aimed to evaluate for the first time a quantitative and qualitative (mixed-method) single-case study design to investigate the use of the e-MMA in other patients on OAT with polypharmacy. Five patients from the OAS participated in a sequential multiple-baseline single subject study. Between November 2014 and August 2015, 3 women and 2 men (mean age 48 years), taking in addition to OAT a median of 7 medications during 3 dosing times per day were included in the study. An intervention phase with intake reminder was implemented for two participants. For both patients completing the intervention phase, taking adherence increased by more than 25% and no missed doses were observed when audible and visual reminders were introduced. Participants generally accepted the e-MMA, especially for the security of having enough medication at home, the possibility to pre-dispense pocket-doses, and the assurance of regular intakes.
Finally, in PROJECT C5, we estimated yearly cost-of-illness (COI) of 109‘611 Swiss Francs (SFr) per patient for patients receiving OAT and polypharmacy, with direct costs accounting for 30% of the total costs. With the novel supply model, total yearly costs per patient increased by SFr 2’509 for repackaging of medication, leasing of the e-MMA, and time spent for travel, refill, and support. Sensitivity analysis showed that the results were robust and overall costs did not substantially change with various estimations.
Despite much research, interventions aimed at improving medication adherence report disappointing and inconsistent results. We aimed to assess congruence between patient characteristics and adherence interventions in PROJECT D. In PROJECT D1, we extracted 42 determinants of non-adherence (26 modifiable and 16 unmodifiable) and 103 interventions from published literature, match the modifiable determinants to interventions like locks and keys, and categorized them into 11 domains.
In Project D2, we applied the results from Project D1 to a Cochrane database with 190 randomized controlled trials on adherence-enhancing interventions. We correlated a congruence score consisting of 6 features related to inclusion criteria, patient characteristics at baseline, and intervention design with intervention effects regarding adherence and clinical outcomes. The inclusion of non-adherent patients was the single feature significantly associated with effective adherence interventions. However, neither the overall congruence score, nor any other individual feature were significantly associated with intervention effects.
Conclusions:
- It was possible to paraphrase definitions of PhC using a standardized syntax focusing on the provider, recipient, subject, outcomes, and activities of PhC practice. During a one-day workshop, experts in PhC research agreed on a definition, intended to be applicable for the present time, representative for various work settings, and valid for countries in- and outside of Europe.
- Tablet splitting is a pharmaceutical care issue with potential consequences on adherence, which plays a major role in dosage adjustments for geriatric patients and is sometimes prescribed against the recommendations from the manufacturer.
- The appearance of MMAs, but also its functionality and the whole medication supply process play an important role with regards to the design and targeting of MMAs. Patients’ living conditions like mobility remain the key determinants for their acceptance of the e-MMA.
- The increase in the number of substances and medications for older drug users might lead to an increased risk for drug-drug interactions, adverse events, and non-adherence. Alternative supply models to assist patients with their medication management and to support medication adherence are needed in particular for older patients with OAT and polypharmacy.
- A novel supply model with an e-MMA may be feasible to simultaneously monitor and improve implementation of dosing regimens for opioid-dependent patients with polypharmacy.
- The use of a mixed-method single-subject design showed promising results for the evaluation of an e-MMA for polypharmacy. Our pilot study showed that the e-MMA may ensure correct implementation of dosing regimens for opioid-substituted patients with polypharmacy when certain prerequisites are considered. Overall, the flexibility of single-subject research designs offers considerable advantages for the evaluation of adherence interventions.
- Cost-of-illness for older patients with OAT and polypharmacy is high, especially when considering indirect costs, such as productivity loss due to disability. According to our cost comparison model, the novel electronic medication supply model increases overall costs marginally, but might offset the costs of more expensive alternatives such as nursing homes.
- 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 patient determinants and be tailored to the unmodifiable patient determinants.
- A 6-item score to assess congruence between patient characteristics and adherence interventions was not significantly associated with intervention effects in 190 RCTs included in a Cochrane review. The presence of only six studies that included non-adherent patients and the inter-dependency of this item with the remaining five precluded a conclusive assessment of congruence between patient characteristics and adherence interventions.
Future research about the e-MMA should aim at:
- developing and implementing robust care models for older patients with polypharmacy and opioid-assisted therapy.
- evaluating the effectiveness of the e-MMA in terms of clinical, humanistic and economic outcomes.
- evaluating the long-term benefits and cost-effectiveness of the novel supply model.
Future research to improve adherence to polypharmacy should aim at:
- providing guidelines for the appropriate design and analyses of single-subject trials in adherence research, including recommendations for statistical analysis.
- developing instruments to reliably assess modifiable and unmodifiable determinants of non-adherence and to select appropriate interventions in research and practice.