Quality and safety of medication use in primary care:consensus validation of a new set of explicit medication assessment criteria and prioritisation of topics for improvement

<p>Background: Addressing the problem of preventable drug related morbidity (PDRM) in primary care is a challenge for health care systems internationally. The increasing implementation of clinical information systems in the UK and internationally provide new opportunities to systematically identify patients at risk of PDRM for targeted medication review. The objectives of this study were (1) to develop a set of explicit medication assessment criteria to identify patients with sub-optimally effective or high-risk medication use from electronic medical records and (2) to identify medication use topics that are perceived by UK primary care clinicians to be priorities for quality and safety improvement initiatives.</p> <p>Methods: For objective (1), a 2-round consensus process based on the RAND/UCLA Appropriateness Method (RAM) was conducted, in which candidate criteria were identified from the literature and scored by a panel of 10 experts for 'appropriateness' and 'necessity'. A set of final criteria was generated from candidates accepted at each level. For objective (2), thematically related final criteria were clustered into 'topics', from which a panel of 26 UK primary care clinicians identified priorities for quality improvement in a 2-round Delphi exercise.</p> <p>Results: (1) The RAM process yielded a final set of 176 medication assessment criteria organised under the domains 'quality' and 'safety', each classified as targeting 'appropriate/necessary to do' (quality) or 'inappropriate/necessary to avoid' (safety) medication use. Fifty-two final 'quality' assessment criteria target patients with unmet indications, sub-optimal selection or intensity of beneficial drug treatments. A total of 124 'safety' assessment criteria target patients with unmet needs for risk-mitigating agents, high-risk drug selection, excessive dose or duration, inconsistent monitoring or dosing instructions. (2) The UK Delphi panel identified 11 (23%) of 47 scored topics as 'high priority' for quality improvement initiatives in primary care.</p> <p>Conclusions: The developed criteria set complements existing medication assessment instruments in that it is not limited to the elderly, can be implemented in electronic data sets and focuses on drug groups and conditions implicated in common and/or severe PDRM in primary care. Identified priorities for quality and safety improvement can guide the selection of targets for initiatives to address the PDRM problem in primary care.</p&gt

Folate augmentation of treatment - Evaluation for depression (FolATED): randomised trial and economic evaluation

Background Folate deficiency is associated with depression. Despite the biological plausibility of a causal link, the evidence that adding folate enhances antidepressant treatment is weak. Objectives (1) Estimate the clinical effectiveness and cost-effectiveness of folic acid as adjunct to antidepressant medication (ADM). (2) Explore whether baseline folate and homocysteine predict response to treatment. (3) Investigate whether response to treatment depends on genetic polymorphisms related to folate metabolism. Design FolATED (Folate Augmentation of Treatment – Evaluation for Depression) was a double-blind and placebo-controlled, but otherwise pragmatic, randomised trial including cost–utility analysis. To yield 80% power of detecting standardised difference on the Beck Depression Inventory version 2 (BDI-II) of 0.3 between groups (a ‘small’ effect), FolATED trialists sought to analyse 358 participants. To allow for an estimated loss of 21% of participants over three time points, we planned to randomise 453. Settings Clinical – Three centres in Wales – North East Wales, North West Wales and Swansea. Trial management – North Wales Organisation for Randomised Trials in Health in Bangor University. Biochemical analysis – University Hospital of Wales, Cardiff. Genetic analysis – University of Liverpool. Participants Four hundred and seventy-five adult patients presenting to primary or secondary care with confirmed moderate to severe depression for which they were taking or about to start ADM, and able to consent and complete assessments, but not (1) folate deficient, vitamin B12 deficient, or taking folic acid or anticonvulsants; (2) misusing drugs or alcohol, or suffering from psychosis, bipolar disorder, malignancy or other unstable or terminal illness; (3) (planning to become) pregnant; or (4) participating in other clinical research. Interventions Once a day for 12 weeks experimental participants added 5 mg of folic acid to their ADM, and control participants added an indistinguishable placebo. All participants followed pragmatic management plans initiated by a trial psychiatrist and maintained by their general medical practitioners. Main outcome measures Assessed at baseline, and 4, 12 and 25 weeks thereafter, and analysed by ‘area under curve’ (main); by analysis of covariance at each time point (secondary); and by multi-level repeated measures (sensitivity analysis): Mental health – BDI-II (primary), Clinical Global Impression (CGI), Montgomery–Åsberg Depression Rating Scale (MADRS), UKU side effects scale, and Mini International Neuropsychiatric Interview (MINI) suicidality subscale; General health – UK 12-item Short Form Health Survey (SF-12), European Quality of Life scale – 5 Dimensions (EQ-5D); Biochemistry – serum folate, B12, homocysteine; Adherence – Morisky Questionnaire; Economics – resource use. Results Folic acid did not significantly improve any of these measures. For example it gained a mean of just 2.9 quality-adjusted life-days [95% confidence interval (CI) from –12.7 to 7.0 days] and saved a mean of just £48 (95% CI from –£292 to £389). In contrast it significantly reduced mental health scores on the SF-12 by 3.0% (95% CI from –5.2% to –0.8%). Conclusions The FolATED trial generated no evidence that folic acid was clinically effective or cost-effective in augmenting ADM. This negative finding is consistent with improving understanding of the one-carbon folate pathway suggesting that methylfolate is a better candidate for augmenting ADM. Hence the findings of FolATED undermine treatment guidelines that advocate folic acid for treating depression, and suggest future trials of methylfolate to augment ADM. Trial registration Current Controlled Trials ISRCTN37558856. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 48. See the HTA programme website for further project information