Using Discrete Choice Experiment to elicit patient preferences for osteoporosis drug treatments: Where to from here?

Osteoporosis is a disease that increases skeletal fracture risk and places a significant health and economic burden on patients, families, and health systems. Many treatment options exist, but patient use is suboptimal, thus undermining the potential cost-effectiveness of treatments. In the previous issue of Arthritis Research & Therapy, Hiligsmann and colleagues expanded the findings of previous studies to report, from a sample of 257 patients with osteoporosis, the preference to trade off clinical outcomes for the amenity provided by convenient dosing regimens. This editorial critiques the strengths and limitations of the methods, discusses the potential utility of patient treatment preferences, and suggests avenues for further research. © 2014 BioMed Central Ltd

Understanding rational non-adherence to medications. A discrete choice experiment in a community sample in Australia

Background: In spite of the potential impact upon population health and expenditure, interventions promoting medication adherence have been found to be of moderate effectiveness and cost effectiveness. Understanding the relative influence of factors affecting patient medication adherence decisions and the characteristics of individuals associated with variation in adherence will lead to a better understanding of how future interventions should be designed and targeted. This study aims to explore medication-taking decisions that may underpin intentional medication non-adherence behaviour amongst a community sample and the relative importance of medication specific factors and patient background characteristics contributing to those decisions. Methods. A discrete choice experiment conducted through a web-enabled online survey was used to estimate the relative importance of eight medication factors (immediate and long-term medication harms and benefits, cost, regimen, symptom severity, alcohol restrictions) on the preference to continue taking a medication. To reflect more closely what usually occurs in practice, non-disease specific medication and health terms were used to mimic decisions across multiple medications and conditions.161 general community participants, matching the national Australian census data (age, gender) were recruited through an online panel provider (participation rate: 10%) in 2010. Results: Six of the eight factors (i.e. immediate and long-term medication harms and benefits, cost, and regimen) had a significant influence on medication choice. Patient background characteristics did not improve the model. Respondents with private health insurance appeared less sensitive to cost then those without private health insurance. In general, health outcomes, framed as a side-effect, were found to have a greater influence over adherence than outcomes framed as therapeutic benefits. Conclusions: Medication-taking decisions are the subject of rational choices, influenced by the attributes of treatments and potentially amenable to intervention through education, strategic pricing and the altering of dosing characteristics. Understanding individual treatment preferences is thus an important step to improving adherence support provision in practice. Re-framing future interventions and policies to support rational and informed individual patient choices, is the way forward to realising the full potential health and economic benefits from the efficacious use of medications. © 2012 Laba et al.; licensee BioMed Central Ltd

Patient preferences for adherence to treatment for osteoarthritis: The MEdication Decisions in Osteoarthritis Study (MEDOS)

Background: Often affecting knee joints, osteoarthritis (OA) is the most common type of arthritis and by 2020 is predicted to become the fourth leading cause of disability globally. Without cure, medication management is symptomatic, mostly with simple analgesics such as acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), and glucosamine sulfate. Adherence to arthritis medications is generally low. Intentional non-adherence, that is deliberate decision-making about the use of analgesics, occurs in OA patients. To date, a limited number of studies have explored medication-taking decisions in people with OA nor the extent to which individuals' trade off one treatment factor for another in their decision-making using quantitative techniques. This study aimed to estimate the relative influence of medication-related factors and respondent characteristics on decisions to continue medications among people with symptomatic OA. Methods. A discrete choice experiment (DCE) was conducted among participants attending end-of-study visits in the Long-term Evaluation of Glucosamine Sulfate (LEGS) study (ClinicalTrials.gov ID: NCT00513422). The paper-based survey was used to estimate the relative importance of seven medication specific factors (pain efficacy, mode of action, dose frequency, treatment schedule, side effects, prescription, and out-of-pocket costs) and respondent characteristics on decisions to continue medications. Results: 188 (response rate 37%) completed surveys were returned. Four of the seven medication factors (side effects, out-of-pocket costs, mode of action, treatment schedule) had a significant effect on the choice to continue medication; patient characteristics did not. Assuming equivalent pain efficacy and disease-modifying properties for glucosamine, the positive relative likelihood of continuing with sustained-release acetaminophen was equivalent to glucosamine. By contrast, the negative relative likelihood of NSAID continuation was mostly driven by the side effect profile. The predicted probability of continuing with glucosamine decreased with increasing out-of-pocket costs. Conclusions: This study has characterised the complexity of medication-taking decisions that potentially underpin intentional non-adherent behaviour for people with symptomatic OA. In particular, medication risks and cost were important and ought to be borne into considerations in interpreting clinical trial evidence for practice. Ultimately addressing these factors may be the way forward to realising the full potential of health and economic benefits from the efficacious and safe use of OA medications. © 2013 Laba et al.; licensee BioMed Central Ltd

Examining the use of process evaluations of randomised controlled trials of complex interventions addressing chronic disease in primary health care-a systematic review protocol

© 2016 The Author(s). Background: Randomised controlled trials (RCTs) of complex interventions in primary health care (PHC) are needed to provide evidence-based programmes to achieve the Declaration of Alma Ata goal of making PHC equitable, accessible and universal and to effectively address the rising burden from chronic disease. Process evaluations of these RCTs can provide insight into the causal mechanisms of complex interventions, the contextual factors, and inform as to whether an intervention is ineffective due to implementation failure or failure of the intervention itself. To build on this emerging body of work, we aim to consolidate the methodology and methods from process evaluations of complex interventions in PHC and their findings of facilitators and barriers to intervention implementation in this important area of health service delivery. Methods: Systematic review of process evaluations of randomised controlled trials of complex interventions which address prevalent major chronic diseases in PHC settings. Published process evaluations of RCTs will be identified through database and clinical trial registry searches and contact with authors. Data from each study will be extracted by two reviewers using standardised forms. Data extracted include descriptive items about (1) the RCT, (2) about the process evaluations (such as methods, theories, risk of bias, analysis of process and outcome data, strengths and limitations) and (3) any stated barriers and facilitators to conducting complex interventions. A narrative synthesis of the findings will be presented. Discussion: Process evaluation findings are valuable in determining whether a complex intervention should be scaled up or modified for other contexts. Publishing this protocol serves to encourage transparency in the reporting of our synthesis of current literature on how process evaluations have been conducted thus far and a deeper understanding of potential challenges and solutions to aid in the implementation of effective interventions in PHC beyond the research setting. Systematic review registration: PROSPERO CRD42016035572

Rapid and substantial increases in anticoagulant use and expenditure in Australia following the introduction of new types of oral anticoagulants

© 2018 Morgan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objectives To quantify changes in anticoagulant use in Australia since the introduction of Non-vitamin K antagonist anticoagulants (NOACs) and to estimate government expenditure. Design Interrupted-time-series analysis quantifying anticoagulant dispensing, before and after first Pharmaceutical Benefits Scheme (PBS) NOAC listing in August 2009 for venous thromboembolism prevention; and expanded listing for stroke prevention in non-valvular atrial fibrillation (AF) in August 2013, up to June 2016. Estimated government expenditure on PBS-listed anticoagulants. Setting and participants PBS dispensing in 10% random sample of Australians, restricted to continuous concessional beneficiaries dispensed oral anticoagulants from July 2005 to June 2016. Total PBS anticoagulant expenditure was calculated using Medicare Australia statistics. Main outcome measures Monthly dispensing and initiation of oral anticoagulants (warfarin, rivaroxaban, dabigatran or apixaban). Annual PBS anticoagulant expenditure. Results An estimated 149,180 concessional beneficiaries were dispensed anticoagulants (100% warfarin) during July 2005. This increased to 292,550 during June 2016, of whom 47.0%, 27.1%, 18.7% and 7.2% were dispensed warfarin, rivaroxaban, apixaban and dabigatran, respectively. Of 16,500 initiated on anticoagulants in June 2016, 24.3%, 38.2%, 30.0% and 7.5% were initiated on warfarin, rivaroxaban, apixaban, and dabigatran, respectively. Compared to July 2005-July 2013, from August 2013-June 2016, dispensings for all anticoagulants increased by 2,303 dispensings/month (p<0.001, 95%CI = [1,229 3,376]); warfarin dispensing decreased by 1,803 dispensings/month (p<0.001, 95%CI = [–2,606, –1,000]). Total PBS anticoagulant expenditure was $19.5 million (97.0$203.3 million (86.2% concessional) in 2015/16, of which 11.2% was warfarin. Conclusions The introduction of the NOACs led to substantial increases in anticoagulant use and expenditure in Australia

The household economic burden of eating disorders and adherence to treatment in Australia

© 2014 Gatt et al.; licensee BioMed Central Ltd. Background: This study investigated the household economic burden of eating disorders and cost-related non-adherence to treatment in Australia. Methods: Multi-centre prospective observational study using a structured questionnaire. Ninety participants were recruited from two clinic settings in New South Wales, Australia and from the community using social media. The primary outcome measures were household economic burden of illness measured in terms of out-of-pocket expenditure, household economic hardship and cost-related non-adherence. Results: The pattern of out-of-pocket expenditure varied by diagnosis, with Bulimia Nervosa associated with the highest total mean expenditure (per three months). Economic hardship was reported in 96.7% of participants and 17.8% reported cost-related non-adherence. Those most likely to report cost-related non-adherence had a longer time since diagnosis. Cost-related non-adherence and higher out-of-pocket expenditure were associated with poorer quality of life, a more threatening perception of the impact of the illness and poor self-reported health. Conclusions: This study is the first to empirically and quantitatively examine the household economic burden of eating disorders from the patient perspective. Results indicate that households experience a substantial burden associated with the treatment and management of an eating disorder. This burden may contribute to maintaining the illness for those who experience cost-related non-adherence and by negatively influencing health outcomes. Current initiatives to implement sustainable and integrated models of care for eating disorders should strive to minimise the economic impact of treatment on families

Process evaluation of a randomised controlled trial of a pharmacological strategy to improve hypertension control: Protocol for a qualitative study

© 2018 Author(s) (or their employer(s)). Introduction Globally, the prevalence of uncontrolled hypertension is high, particularly in low- and middle-income countries. There is a critical need for strategies to improve hypertension control. The early use of a fixed low-dose combination of three antihypertensive drugs (triple pill) has the potential to significantly improve hypertension control. The TRI ple Pill vs. U sual care M anagement for P atients with mild-to- moderate H ypertension (TRIUMPH) randomised controlled trial (RCT) is designed to test the effects of this strategy compared with usual care in patients with mild-to-moderate hypertension. This paper reports the protocol of a process evaluation of the TRIUMPH RCT. The objectives are to understand factors related to implementation of the intervention, mechanisms of effect, contextual factors that underpin the effectiveness of the triple pill strategy and the potential barriers and facilitators to implementing the strategy in clinical practice. Methods and analysis Face-to-face semistructured in-depth interviews with a purposive sample of TRIUMPH RCT participants and healthcare professionals in Sri Lanka will be conducted. Healthcare professionals will include physicians and their staff who were involved in conducting the TRIUMPH RCT. Interviewees will be recruited sequentially until thematic saturation is achieved. Interviews will be audio recorded, transcribed verbatim and analysed in NVivo using framework analysis methods. Ethics and dissemination The TRIUMPH RCT and process evaluation have received approval from the relevant Ethics Review Committee. All participants will be asked to provide written consent before participation. Findings from the study will be disseminated through publications and conference presentations

Implementing Kanyini GAP, a pragmatic randomised controlled trial in Australia: Findings from a qualitative study

© 2015 Liu et al. Background: Pragmatic randomised controlled trials (PRCTs) aim to assess intervention effectiveness by accounting for 'real life' implementation challenges in routine practice. The methodological challenges of PRCT implementation, particularly in primary care, are not well understood. The Kanyini Guidelines Adherence to Polypill study (Kanyini GAP) was a recent primary care PRCT involving multiple private general practices, Indigenous community controlled health services and private community pharmacies. Through the experiences of Kanyini GAP participants, and using data from study materials, this paper identifies the critical enablers and barriers to implementing a PRCT across diverse practice settings and makes recommendations for future PRCT implementation. Methods: Qualitative data from 94 semi-structured interviews (47 healthcare providers (pharmacists, general practitioners, Aboriginal health workers; 47 patients) conducted for the process evaluation of Kanyini GAP was used. Data coded to 'trial impact', 'research motivation' and 'real world' were explored and triangulated with data extracted from study materials (e.g. Emails, memoranda of understanding and financial statements). Results: PRCT implementation was facilitated by an extensive process of relationship building at the trial outset including building on existing relationships between core investigators and service providers. Health providers' and participants' altruism, increased professional satisfaction, collaboration, research capacity and opportunities for improved patient care enabled implementation. Inadequate research infrastructure, excessive administrative demands, insufficient numbers of adequately trained staff and the potential financial impact on private practice were considered implementation barriers. These were largely related to this being the first experience of trial involvement for many sites. The significant costs of addressing these barriers drew study resources from the task of achieving recruitment targets. Conclusions: Conducting PRCTs is crucial to generating credible evidence of intervention effectiveness in routine practice. PRCT implementation needs to account for the particular challenges of implementing collaborative research across diverse stakeholder organisations. Reliance on goodwill to participate is crucial at the outset. However, participation costs, particularly for organisations with little or no research experience, can be substantial and should be factored into PRCT funding models. Investment in a pool to fund infrastructure in the form of primary health research networks will offset some of these costs, enabling future studies to be implemented more cost-effectively. Trial registration:ACTRN12608000583334

Generating real-world evidence on the quality use, benefits and safety of medicines in australia: History, challenges and a roadmap for the future

Australia spends more than $20 billion annually on medicines, delivering significant health benefits for the population. However, inappropriate prescribing and medicine use also result in harm to individuals and populations, and waste of precious health resources. Medication data linked with other routine collections enable evidence generation in pharmacoepidemiology; the science of quantifying the use, effectiveness and safety of medicines in real-world clinical practice. This review details the history of medicines policy and data access in Australia, the strengths of existing data sources, and the infrastructure and governance enabling and impeding evidence generation in the field. Currently, substantial gaps persist with respect to cohesive, contemporary linked data sources supporting quality use of medicines, effectiveness and safety research; exemplified by Aus-tralia’s limited capacity to contribute to the global effort in real-world studies of vaccine and dis-ease-modifying treatments for COVID-19. We propose a roadmap to bolster the discipline, and population health more broadly, underpinned by a distinct capability governing and streamlining access to linked data assets for accredited researchers. Robust real-world evidence generation requires current data roadblocks to be remedied as a matter of urgency to deliver efficient and equitable health care and improve the health and well-being of all Australians

Assessing the impact of a combined nutrition counselling and cash transfer intervention on women’s empowerment in rural Bangladesh: a randomised control trial protocol

Introduction There is growing interest in assessing the impact of health interventions, particularly when women are the focus of the intervention, on women’s empowerment. Globally, research has shown that interventions targeting nutrition, health and economic development can affect women’s empowerment. Evidence suggests that women’s empowerment is also an underlying determinant of nutrition outcomes. Depending on the focus of the intervention, different domains of women’s empowerment will be influenced, for example, an increase in nutritional knowledge, or greater control over income and access to resources. Objective This study evaluates the impact of the Shonjibon Cash and Counselling (SCC) Trial that combines nutrition counselling and an unconditional cash transfer, delivered on a mobile platform, on women’s empowerment in rural Bangladesh. Methods and analysis We will use a mixed-methods approach, combining statistical analysis of quantitative data from 2840 women in a cluster randomised controlled trial examining the impact of nutrition behaviour change communications (BCCs) and cash transfers on child undernutrition. Pregnant participants will be given a smartphone with a customised app, delivering nutrition BCC messages, and will receive nutrition counselling via a call centre and an unconditional cash transfer. This study is a component of the SCC Trial and will measure women’s empowerment using a composite indicator based on the Project-Level Women’s Empowerment in Agriculture Index, with quantitative data collection at baseline and endline. Thematic analysis of qualitative data, collected through longitudinal interviews with women, husbands and mothers-in-law, will elicit a local understanding of women’s empowerment and the linkages between the intervention and women’s empowerment outcomes. This paper describes the study protocol to evaluate women’s empowerment in a nutrition-specific and sensitive intervention using internationally validated, innovative tools and will help fill the evidence gap on pathways of impact, highlighting areas to target for future programming. Ethics and dissemination Ethical approval has been obtained from the International Centre for Diarrhoeal Disease Research (Ref. PR 17106) and The University of Sydney (Ref: 2019/840). Findings from this study will be shared in Bangladesh with dissemination sessions in-country and internationally at conferences, and will be published in peer-reviewed journals