A framework for understanding sources of bias in medication adherence research.

The sources of bias in medication adherence research have not been comprehensively explored. We aimed to identify biases expected to affect adherence research and to develop a framework for mapping these onto the phases of adherence (initiation, implementation and discontinuation). A literature search was conducted, key papers were reviewed and a Catalogue of Bias was consulted. The specific biases related to adherence measurement and metrics were mapped onto the phases of adherence using a tabular matrix. Twenty-three biases were identified, of which 11 were specifically relevant to adherence measures and metrics. The mapping framework showed differences in the numbers and types of biases associated with each measure and metric while highlighting those common to many adherence study designs (e.g., unacceptability bias and apprehension bias). The framework will inform the design of adherence studies and the development of risk of bias tools for adherence research.

The pharmacokinetics of metformin in patients receiving intermittent haemodialysis.

The aims of this study were to characterise the population pharmacokinetics of metformin in patients receiving haemodialysis, and to determine the doses that will maintain median metformin plasma concentrations below 5 mg L-1 for a typical individual. Metformin plasma concentrations from 5 patients receiving thrice weekly intermittent haemodialysis followed by metformin 500 mg postdialysis were fitted to a published pharmacokinetic model. Additional models to describe the dialytic pharmacokinetics of metformin were explored. Doses of 250 and 500 postdialysis were simulated from the model for a typical haemodialysis patient. The published 2-compartment pharmacokinetic model with an additional parameter to describe haemodialysis clearance provided a reasonable fit to the data. Deterministic simulations from the model for a typical individual suggest that metformin doses of 250-500 mg postdialysis and 250 mg given once daily should maintain median metformin plasma concentrations below 5 mg L-1 .

Clinical interventions to improve adherence to urate-lowering therapy in patients with gout: a systematic review.

The aim of this study was to systematically review and compare the quantitative effect of clinical interventions designed to improve adherence to urate-lowering therapy. MEDLINE, Embase, CINAHL, Scopus and Web of Science were searched for interventional studies reporting quantitative adherence to urate-lowering therapy information as an endpoint. Intervention details, quantitative adherence information, clinical outcome and cost-effectiveness data were extracted. Risk of bias was assessed. From 4721 records, 11 studies (3 randomised and 8 observational) met the inclusion criteria. Pharmacist- and nurse-led interventions were described, involving a mixture of patient education, telephone or mobile texting reminders, and medication blister packing. Quantitative adherence information was obtained using methods such as patient self-reporting and pharmacy-dispensing data. Most studies had a moderate-to-high risk of bias. Two of the three randomised studies reported improvement in adherence between the intervention and control groups, including a 13% increase in the mean proportion of days covered >0.8 [341/681 participants (50%) versus 289/782 participants (37%)] and an 88% increase in achieving a high Medicine Taking Behaviour questionnaire score [37/42 participants (88.1%) versus 0/40 participants (0%)]. Four of the eight observational studies reported improved adherence from baseline (ranging from 33% to 91% based on the longitudinal change in adherence metrics reported). A comparison of the different types of interventions was not feasible due to the heterogeneity between study designs and adherence metrics used. These findings support the need for more interventional studies to be conducted to aid adherence management.