Cost-effectiveness and Cost-utility of the Adherence Improving Self-management Strategy in Human Immunodeficiency Virus Care: A Trial-based Economic Evaluation.

Background: Several promising human immunodeficiency virus (HIV) treatment adherence interventions have been identified, but data about their cost-effectiveness are lacking. This study examines the trial-based cost-effectiveness and cost-utility of the proven-effective Adherence Improving Self-Management Strategy (AIMS), from a societal perspective, with a 15-month time horizon. Methods: Treatment-naive and treatment-experienced patients at risk for viral rebound were randomized to treatment as usual (TAU) or AIMS in a multicenter randomized controlled trial in the Netherlands. AIMS is a nurse-led, 1-on-1 self-management intervention incorporating feedback from electronic medication monitors, delivered during routine clinical visits. Main outcomes were costs per reduction in log10 viral load, treatment failure (2 consecutive detectable viral loads), and quality-adjusted life-years (QALYs). Results: Two hundred twenty-three patients were randomized. From a societal perspective, AIMS was slightly more expensive than TAU but also more effective, resulting in an incremental cost-effectiveness ratio (ICER) of €549 per reduction in log10 viral load and €1659 per percentage decrease in treatment failure. In terms of QALYs, AIMS resulted in higher costs but more QALYs compared to TAU, which resulted in an ICER of €27759 per QALY gained. From a healthcare perspective, AIMS dominated TAU. Additional sensitivity analyses addressing key limitations of the base case analyses also suggested that AIMS dominates TAU. Conclusions: Base case analyses suggests that over a period of 15 months, AIMS may be costlier, but also more effective than TAU. All additional analyses suggest that AIMS is cheaper and more effective than TAU. This trial-based economic evaluation confirms and complements a model-based economic evaluation with a lifetime horizon showing that AIMS is cost-effective. Clinical Trials Registration: NCT01429142.

Clinical effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy: a study protocol for a pragmatic cluster randomised trial.

INTRODUCTION: Hepatitis C virus (HCV) infection affects 0.7% of the general population, and up to 40% of people prescribed opioid substitution therapy (OST) in Scotland. In conventional care, less than 10% of OST users are tested for HCV and less than 25% of these initiate treatment. Community pharmacists see this group frequently to provide OST supervision. This study examines whether a pharmacist-led 'test & treat' pathway increases cure rates for HCV. METHODS AND ANALYSIS: This protocol describes a cluster-randomised trial where 60 community pharmacies provide either conventional or pharmacy-led care. All pharmacies offer dried blood spot testing (DBST) for HCV. Participants have attended the pharmacy for OST for 3 months; are positive for HCV genotype 1 or 3; are not co-infected with HIV and/or hepatitis B; have no decompensated liver disease; are not pregnant. For conventional care, pharmacists refer HCV-positive participants to a local centre for assessment. In the pharmacy-led arm, pharmacists assess participants themselves in the pharmacy. Drug prescribing is by nurse prescribers (conventional arm) or pharmacist prescribers (pharmacy-led arm). Treatment in both arms is delivered as daily modified directly observed therapy in a pharmacy. Primary trial outcome is number of sustained virological responses at 12 weeks after treatment completion. Secondary trial outcomes are number of tests taken; treatment uptake; completion; adherence; re-infection. An economic evaluation will assess potential cost-effectiveness. Qualitative research interviews with clients and health professionals assess acceptability of a pharmacist-led pathway. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the East of Scotland Research Ethics Committee 2 (15/ES/0086) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Caldicott guardian approval was given on 16 December 2016 to allow NHS Tayside to pass information to the cluster community pharmacies about the HCV test status of patients that they are seeing to provide OST supervision. NHS R&D approvals have been obtained from each health board taking part in the study. Informed consent is obtained before study enrolment and only anonymised data are stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT02706223; Pre-results.

Pharmacist services for non-hospitalised patients.

BACKGROUND: This review focuses on non-dispensing services from pharmacists, i.e. pharmacists in community, primary or ambulatory-care settings, to non-hospitalised patients, and is an update of a previously-published Cochrane Review. OBJECTIVES: To examine the effect of pharmacists' non-dispensing services on non-hospitalised patient outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases and two trial registers in March 2015, together with reference checking and contact with study authors to identify additional studies. We included non-English language publications. We ran top-up searches in January 2018 and have added potentially eligible studies to 'Studies awaiting classification'. SELECTION CRITERIA: Randomised trials of pharmacist services compared with the delivery of usual care or equivalent/similar services with the same objective delivered by other health professionals. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures of Cochrane and the Effective Practice and Organisation of Care Group. Two review authors independently checked studies for inclusion, extracted data and assessed risks of bias. We evaluated the overall certainty of evidence using GRADE. MAIN RESULTS: We included 116 trials comprising 111 trials (39,729 participants) comparing pharmacist interventions with usual care and five trials (2122 participants) comparing pharmacist services with services from other healthcare professionals. Of the 116 trials, 76 were included in meta-analyses. The 40 remaining trials were not included in the meta-analyses because they each reported unique outcome measures which could not be combined. Most trials targeted chronic conditions and were conducted in a range of settings, mostly community pharmacies and hospital outpatient clinics, and were mainly but not exclusively conducted in high-income countries. Most trials had a low risk of reporting bias and about 25%-30% were at high risk of bias for performance, detection, and attrition. Selection bias was unclear for about half of the included studies.Compared with usual care, we are uncertain whether pharmacist services reduce the percentage of patients outside the glycated haemoglobin target range (5 trials, N = 558, odds ratio (OR) 0.29, 95% confidence interval (CI) 0.04 to 2.22; very low-certainty evidence). Pharmacist services may reduce the percentage of patients whose blood pressure is outside the target range (18 trials, N = 4107, OR 0.40, 95% CI 0.29 to 0.55; low-certainty evidence) and probably lead to little or no difference in hospital attendance or admissions (14 trials, N = 3631, OR 0.85, 95% CI 0.65 to 1.11; moderate-certainty evidence). Pharmacist services may make little or no difference to adverse drug effects (3 trials, N = 590, OR 1.65, 95% CI 0.84 to 3.24) and may slightly improve physical functioning (7 trials, N = 1329, mean difference (MD) 5.84, 95% CI 1.21 to 10.48; low-certainty evidence). Pharmacist services may make little or no difference to mortality (9 trials, N = 1980, OR 0.79, 95% CI 0.56 to 1.12, low-certaintly evidence).Of the five studies that compared services delivered by pharmacists with other health professionals, no studies evaluated the impact of the intervention on the percentage of patients outside blood pressure or glycated haemoglobin target range, hospital attendance and admission, adverse drug effects, or physical functioning. AUTHORS' CONCLUSIONS: The results demonstrate that pharmacist services have varying effects on patient outcomes compared with usual care. We found no studies comparing services delivered by pharmacists with other healthcare professionals that evaluated the impact of the intervention on the six main outcome measures. The results need to be interpreted cautiously because there was major heterogeneity in study populations, types of interventions delivered and reported outcomes.There was considerable heterogeneity within many of the meta-analyses, as well as considerable variation in the risks of bias.

What are the current challenges of managing cancer pain and could digital technologies help?

OBJECTIVES: Pain remains a problem for people with cancer despite effective treatments being available. We aimed to explore current pain management strategies used by patients, caregivers and professionals and to investigate opportunities for digital technologies to enhance cancer pain management. METHODS: A qualitative study comprising semistructured interviews and focus groups. Patients with cancer pain, their caregivers and health professionals from Northeast Scotland were recruited from a purposive sample of general practices. Professionals were recruited from regional networks. RESULTS: Fifty one participants took part in 33 interviews (eight patients alone, six patient/caregiver dyads and 19 professionals) and two focus groups (12 professionals). Living with cancer was hard work for patients and caregivers and comparable to a 'full-time job'. Patients had personal goals which involved controlling pain intensity and balancing this with analgesic use, side effects, overall symptom burden and social/physical activities.Digital technologies were embraced by most patients, and made living life with advanced cancer easier and richer (eg, video calls with family). Technology was underutilised for pain and symptom management. There were suggestions that technology could support self-monitoring and communicating problems to professionals, but patients and professionals were concerned about technological monitoring adding to the work of managing illness. CONCLUSIONS: Cancer pain management takes place in the context of multiple, sometimes competing personal goals. It is possible that technology could be used to help patients share individual symptom experiences and goals, thus enhancing tailored care. The challenge is for digital solutions to add value without adding undue burden.

Effectiveness and cost-effectiveness of a nurse-delivered intervention to improve adherence to treatment for HIV: a pragmatic, multicentre, open-label, randomised clinical trial.

BACKGROUND: No high-quality trials have provided evidence of effectiveness and cost-effectiveness of HIV treatment adherence intervention strategies. We therefore examined the effectiveness and cost-effectiveness of the Adherence Improving self-Management Strategy (AIMS) compared with treatment as usual. METHODS: We did a pragmatic, multicentre, open-label, randomised controlled trial in seven HIV clinics at academic and non-academic hospitals in the Netherlands. Eligible participants were patients with HIV who were either treatment experienced (ie, with ≥9 months on combination antiretroviral therapy [ART] and at risk of viral rebound) or treatment-naive patients initiating their first combination ART regimen. We randomly assigned participants (1:1) to either AIMS or treatment as usual (ie, containing a range of common adherence intervention strategies) using a computer-generated randomisation table. Randomisation was stratified by treatment experience (experienced vs naive) and included block randomisation at nurse level with randomly ordered blocks of size four, six, and eight. 21 HIV nurses from the participating clinics received three training sessions of 6 h each (18 h in total) on AIMS and a 1·5 h booster training session at the clinic (two to three nurses per session) after each nurse had seen two to three patients. AIMS was delivered by nurses during routine clinic visits. We did mixed-effects, intent-to-treat analyses to examine treatment effects on the primary outcome of log10 viral load collected at months 5, 10, and 15. The viral load results were exponentiated (with base 10) for easier interpretation. Using cohort data from 7347 Dutch patients with HIV to calculate the natural course of illness, we developed a lifetime Markov model to estimate the primary economic outcome of lifetime societal costs per quality-adjusted life-years (QALYs) gained. This trial is registered at ClinicalTrials.gov (number NCT01429142). FINDINGS: We recruited participants between Sept 1, 2011, and April 2, 2013; the last patient completed the study on June 16, 2014. The intent-to-treat sample comprised 221 patients; 109 assigned to AIMS and 112 to treatment as usual. Across the three timepoints (months 5, 10, and 15), log viral load was 1·26 times higher (95% CI 1·04-1·52) in the treatment-as-usual group (estimated marginal mean 44·5 copies per mL [95% CI 35·5-55·9]) than in the AIMS group (estimated marginal mean 35·4 copies per mL [29·9-42·0]). Additionally, AIMS was cost-effective (ie, dominant: cheaper and more effective) since it reduced lifetime societal costs by €592 per patient and increased QALYs by 0·034 per patient. INTERPRETATION: Findings from preparatory studies have shown that AIMS is acceptable, feasible to deliver in routine care, and has reproducible effects on medication adherence. In this study, AIMS reduced viral load, increased QALYs, and saved resources. Implementation of AIMS in routine clinical HIV care is therefore recommended. FUNDING: Netherlands Organisation for Health Research and Development.

Reducing the risk of bias in health behaviour change trials: improving trial design, reporting or bias assessment criteria? A review and case study.

OBJECTIVE: It has been suggested that randomised controlled trials (RCTs) of health behaviour change (HBC) interventions are less rigorously designed than - for example- drug trials. This study presents an approach to clarifying whether this is due to poor trial design, incomplete trial reporting and/or the inappropriateness of commonly applied risk of bias assessment criteria. DESIGN: First, a framework of key sources of bias and common strategies for reducing bias risk is developed based on a literature review. Second, we describe the design of a multi-site RCT evaluating the cost-effectiveness of an HIV-treatment adherence intervention (case study). The choices made by the multidisciplinary team trying to minimise the risk of bias are compared against the risk of bias framework. MAIN OUTCOME MEASURES: Implementation of common strategies for reducing the risk of bias in the case study; alternative or additional strategies applied; a justification for each deviation from the risk of bias framework. RESULTS: Most of the common strategies for reducing the risk of bias could be implemented. Alternative strategies were developed for minimising the risk of performance bias and contamination. Several additional, domain-specific risk of bias strategies were implemented. CONCLUSIONS: The literature provides useful guidance for reducing the risk of bias in HBC trials. Yet, the case study suggests that HBC trial designers may face specific challenges that require alternative/additional measures for reducing the risk of bias. Using the risk of bias justification table (RATIONALE) could lead to better-designed HBC trials, more comprehensive trial reports and the data necessary for evaluating the appropriateness of commonly applied risk of bias assessment criteria to HBC trials.

Looking Beyond Health-Related Quality of Life: Predictors of Subjective Well-Being among People Living with HIV in the Netherlands.

Health care interventions are increasingly expected to improve subjective well-being (SWB) rather than health-related quality of life (HRQOL) only. However, little is known about how HRQOL and other relevant quality of life (QOL) domains relate to SWB among people living with HIV. People living with HIV treated in Dutch HIV centers (n = 191) completed a cross-sectional survey on SWB, HRQOL, and other QOL domains (social, financial, sexual, and environmental well-being). In bivariate analyses, all QOL domains were significantly related to SWB (r = .17 to .42). In structural equation models, physical health (ß = .14; p < .05), mental health (ß = .27; p < .01), and environmental well-being (ß = .41; p < .01) directly predicted SWB, while financial and social well-being explained SWB indirectly. Thus, environmental well-being and mental health are the main predictors of SWB, and physical health, social well-being, and financial well-being to a lesser extent. Given that most of HIV-care is directed at improving physical health, from the perspective of promoting SWB HIV care should also be directed at other life domains.

Cost effectiveness of medication adherence-enhancing interventions: a systematic review of trial-based economic evaluations.

BACKGROUND: In light of the pressure to reduce unnecessary healthcare expenditure in the current economic climate, a systematic review that assesses evidence of cost effectiveness of adherence-enhancing interventions would be timely. OBJECTIVE: Our objective was to examine the cost effectiveness of adherence-enhancing interventions compared with care as usual in randomised controlled trials, and to assess the methodological quality of economic evaluations. METHODS: MEDLINE, PsycInfo, EconLit and the Centre for Reviews and Dissemination databases were searched for randomised controlled trials reporting full economic evaluations of adherence-enhancing interventions (published up to June 2013). Information was collected on study characteristics, cost effectiveness of treatment alternatives, and methodological quality. RESULTS: A total of 14 randomised controlled trials were included. The quality of economic evaluations and the risk of bias varied considerably between trials. Four studies showed incremental cost-effectiveness ratios (ICERs) below the willingness-to-pay threshold. Few studies seemed to evaluate interventions that successfully changed adherence. CONCLUSIONS: Only 14 randomised controlled trials examined the cost effectiveness of adherence interventions. Despite that some studies showe favourable ICERs, the overall quality of studies was modest and the economic perspectives applied were frequently narrow. To demonstrate that adherence interventions can be cost effective, we recommend that proven-effective adherence programmes are subjected to comprehensive economic evaluations.

Cost-effectiveness of a nurse-based intervention (AIMS) to improve adherence among HIV-infected patients: design of a multi-centre randomised controlled trial.

BACKGROUND: Non-adherence to HIV-treatment can have a negative impact on patients treatment success rates, quality of life, infectiousness, and life expectancy. Few adherence interventions have shown positive effects on adherence and/or virologic outcomes. The theory- and evidence-based Adherence Improving self-Management Strategy (AIMS) is an intervention that has been demonstrated to improve adherence and viral suppression rates in a randomised controlled trial. However, evidence of its cost-effectiveness is lacking. Following a recent review suggesting that cost-effectiveness evaluations of adherence interventions for chronic diseases are rare, and that the methodology of such evaluations is poorly described in the literature, this manuscript presents the study protocol for a multi-centre trial evaluating the effectiveness and cost-effectiveness of AIMS among a heterogeneous sample of patients. METHODS/DESIGN: The study uses a multi-centre randomised controlled trial design to compare the AIMS intervention to usual care from a societal perspective. Embedded in this RCT is a trial-based and model-based economic evaluation. A planned number of 230 HIV-infected patients are randomised to receive either AIMS or usual care. The relevant outcomes include changes in adherence, plasma viral load, quality of life, and societal costs. The time horizon for the trial-based economic evaluation is 12-15 months. Costs and effects are extrapolated to a lifetime horizon for the model-based economic evaluation. DISCUSSION: The present multicentre RCT is designed to provide sound methodological evidence regarding the effectiveness and cost-effectiveness of a nurse-based counselling intervention (AIMS) to support treatment adherence among a large and heterogeneous sample of HIV-infected patients in the Netherlands. The objective of the current paper is to describe the trial protocol in sufficient detail to allow full evaluation of the quality of the study design. It is anticipated that, if proven cost-effective, AIMS can contribute to improved evidence-based counselling guidelines for HIV-nurses and other health care professionals. TRIAL REGISTRATION: The study has been registered on clinicaltrials.gov (Identifier: NCT01429142).

Stressors and resources mediate the association of socioeconomic position with health behaviours.

BACKGROUND: Variability in health behaviours is an important cause of socioeconomic health disparities. Socioeconomic differences in health behaviours are poorly understood. Previous studies have examined whether (single) stressors or psychosocial resources mediate the relationship between socioeconomic position and health or mortality. This study examined: 1) whether the presence of stressors and the absence of resources can be represented by a single underlying factor, and co-occur among those with lower education, 2) whether stressors and resources mediated the relation between education and health behaviours, and 3) addressed the question whether an aggregate measure of stressors and resources has an added effect over the use of individual measures. METHODS: Questionnaire data on sociodemographic variables, stressors, resources, and health behaviours were collected cross-sectionally among inhabitants (n = 3050) of a medium-sized Dutch city (Utrecht). Descriptive statistics and bootstrap analyses for multiple-mediator effects were used to examine the role of stressors and resources in mediating educational associations with health behaviours. RESULTS: Higher levels of stressors and lower levels of resources could be represented by a single underlying factor, and co-occurred among those with lower educational levels. Stressors and resources partially mediated the relationship between education and four health- behaviours (exercise, breakfast frequency, vegetable consumption and smoking). Financial stress and poor perceived health status were mediating stressors, and social support a strong mediating resource. An aggregate measure of the stressors and resources showed similar associations with health behaviours compared to the summed individual measures. CONCLUSIONS: Lower educated groups are simultaneously affected by the presence of various stressors and absence of multiple resources, which partially explain socioeconomic differences in health behaviours. Compared to the direct associations of stressors and resources with health behaviours, the association with socioeconomic status was modest. Therefore, besides addressing structural inequalities, interventions promoting financial management, coping with chronic disease, and social skills training have the potential to benefit large parts of the population, most notably the lower educated. Further research is needed to clarify how stressors and resources impact health behaviours, why this differs between behaviours and how these disparities could be alleviated.