Innovations in pharmacovigilance studies of medicines in older people.

Pharmacovigilance is defined by the World Health Organization as "the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine/vaccine related problem". Pharmacovigilance studies are critical for detecting and assessing adverse events of medicines that may not have been observed in clinical trials. This activity is especially important in older people who are often excluded from clinical trials as they have multiple chronic conditions and use multiple medicines for longer durations than the clinical trials. In this narrative review we describe innovative methods in pharmacovigilance studies of medicines in older people that leverage the increasing availability of digital health technologies, electronic health records and real-world health data to identify and quantify medication related harms in older people.

Utilisation of Chronic Disease and Mental Health Management Services and Cardioprotective Medication Prescriptions in Primary Care for Patients With Cardiovascular Diseases and Cancer: A Cross-Sectional Study.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Mental health is considered an important risk factor affecting the treatment of cardiovascular disease. However, little is known about the use of secondary prevention strategies for CVD in patients with both cancer and CVD. This study aimed to compare the utilisation of primary care chronic disease management plans, mental health care and guideline-indicated cardioprotective medications among CVD patients with and without cancer. METHODS: Retrospective cross-sectional study utilising clinical data of patients with CVD from 50 Australian primary care practices. Outcomes included the use of chronic disease management plans, mental health care, guideline-indicated cardioprotective medications and influenza vaccination. Logistic regression, accounting for demographic and clinical covariates and clustering effects by practices, was used to compare the two groups. RESULTS: Of the 15,040 patients with CVD, 1,486 patients (9.9%) concurrently had cancer. Patients with cancer, compared to those without, were older (77.6 vs 71.8 years, p<0.001), more likely to drink alcohol (62.6% vs 55.7%, p<0.001), have lower systolic (130.3±17.8 vs 132.5±21.1 mmHg, p<0.001) and diastolic (72.2±11 vs 75.3±34 mmHg, p<0.001) blood pressure. Although suboptimal for both groups, patients with cancer were significantly more likely to have general practice management plans (GPMPs) (51.4% vs 43.2%, p<0.001), coordination of team care arrangements (TCAs) (46.2% vs 37.0%, p<0.001), have a review of either GPMP or TCA (42.8% vs 34.7%, p<0.001), have a mental health treatment consultation (15.4% vs 10.5%, p=0.004) and be prescribed blood pressure-lowering medications (70.1% vs 66.0%, p=0.002). However, there were no statistical differences in the prescription of lipid-lowering or antiplatelet medications. After adjustments for covariates and multiple testing, patients with cancer did not show a difference in GPMPs, TCAs, and a review of either, but were more likely to receive mental health treatment consultations than those without cancer (odds ratio 1.76; 95% confidence interval 1.42-2.19). CONCLUSIONS: Less than half of patients with CVD had a GPMP, TCA or review of either. Although those patients with cancer were more likely to receive these interventions, still around half the patients did not. Medicare-funded GPMPs, TCAs and a review of either GPMP or TCA were underutilised, and future studies should seek to identify ways of improving access to these services.

The financial burden of accessing care for people with scleroderma in Canada: a patient-oriented, cross-sectional survey.

BACKGROUND: Patients with scleroderma require a lifetime of treatment and frequent contacts with rheumatologists and other health care professionals. Although publicly funded health care systems in Canada cover many costs, patients may still face a substantial financial burden in accessing care. The purpose of this study was to quantify out-of-pocket costs borne by people with scleroderma in Canada and compare this burden for those living in large communities and smaller communities. METHODS: We analyzed responses to a Web-based survey of people living in Canada with scleroderma. Respondents reported annual out-of-pocket medical, travel and accommodation and other nonmedical costs (2019 Canadian dollars). We used descriptive statistics to describe travel distance and out-of-pocket costs. We used a 2-part model to estimate the impact on out-of-pocket costs of living in a large urban centre (≥ 100 000 population), compared with smaller urban centres or rural areas (< 100 000 population). We generated combined mean estimates from the 2-part models using predictive margins. RESULTS: The survey included 120 people in Canada with scleroderma. The mean, annual, total out-of-pocket costs were $3357 (standard deviation $5580). Respondents living in smaller urban centres and rural areas reported higher mean total costs ($4148, 95% confidence interval [CI] $3618-$4680) and travel or accommodation costs ($1084, 95% CI $804-$1364) than those in larger urban centres (total costs $2678, 95% CI $2252-$3104; travel or accommodation costs $332, 95% CI $207-$458). INTERPRETATION: Many patients with scleroderma incur considerable out-of-pocket costs, and this burden is exacerbated for those living in smaller urban centres and rural areas. Health care systems and providers should consider ways to alleviate this burden and support equitable access to care.

Prescription drug monitoring programs evaluation: A systematic review of reviews.

BACKGROUND: Prescription drug monitoring programs (PDMPs) are used to mitigate harms from high-risk medicines including misuse, prescription shopping, overdoses, and death. Previous systematic reviews report inconsistent findings. We undertook a systematic review of reviews to 1) describe and identify the methods and outcome measures used to evaluate PDMPs, 2) summarise existing evidence on outcomes and factors that influence PDMP success or benefit realisation. METHODS: MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, and PROSPERO were used to identify systematic reviews on PDMPs. Twelve papers met the inclusion criteria. Data extracted included review aim, study designs, settings, outcome measures, and key findings. Quality was assessed using AMSTAR 2 quality assessment tool. RESULTS: Review papers were categorised as outcome or process evaluation reviews. Process evaluation reviews described implementation processes, barriers and facilitators to PDMP use and/or implementation. Most (57%) papers described barriers which frequently included usability and data integration. Outcome evaluation papers reported impact of PDMPs on outcomes, which were opioid-focused, and findings were highly variable. Most reviews (67%) were rated as low quality, limiting the conclusions that can be drawn. CONCLUSIONS: Inconsistent methods and outcome measures were used to evaluate PDMPs. No economic evaluations of PDMPs were found. Standardising assessment and reporting of results may improve the quality and confidence in an evidence-base to inform future roll-out and evaluation of PDMPs. Targeting barriers such as system-related challenges and negative end-user perceptions could improve sustained uptake of PDMPs, and potentially facilitate benefits realisation, including mitigating harms of high-risk prescription medicines.

Improving rural and regional access to long-acting reversible contraception and medical abortion through nurse-led models of care, task-sharing and telehealth (ORIENT): a protocol for a stepped-wedge pragmatic cluster-randomised controlled trial in Australian general practice.

INTRODUCTION: Women living in rural and regional Australia often experience difficulties in accessing long-acting reversible contraception (LARC) and medical abortion services. Nurse-led models of care can improve access to these services but have not been evaluated in Australian general practice. The primary aim of the ORIENT trial (ImprOving Rural and regIonal accEss to long acting reversible contraceptioN and medical abortion through nurse-led models of care, Tasksharing and telehealth) is to assess the effectiveness of a nurse-led model of care in general practice at increasing uptake of LARC and improving access to medical abortion in rural and regional areas. METHODS AND ANALYSIS: ORIENT is a stepped-wedge pragmatic cluster-randomised controlled trial. We will enrol 32 general practices (clusters) in rural or regional Australia, that have at least two general practitioners, one practice nurse and one practice manager. The nurse-led model of care (the intervention) will be codesigned with key women's health stakeholders. Clusters will be randomised to implement the model sequentially, with the comparator being usual care. Clusters will receive implementation support through clinical upskilling, educational outreach and engagement in an online community of practice. The primary outcome is the change in the rate of LARC prescribing comparing control and intervention phases; secondary outcomes include change in the rate of medical abortion prescribing and provision of related telehealth services. A within-trial economic analysis will determine the relative costs and benefits of the model on the prescribing rates of LARC and medical abortion compared with usual care. A realist evaluation will provide contextual information regarding model implementation informing considerations for scale-up. Supporting nurses to work to their full scope of practice has the potential to increase LARC and medical abortion access in rural and regional Australia. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Monash University Human Research Ethics Committee (Project ID: 29476). Findings will be disseminated via multiple avenues including a knowledge exchange workshop, policy briefs, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000086763).

Age-Related Variation in the Provision of Primary Care Services and Medication Prescriptions for Patients with Cardiovascular Disease.

As population aging progresses, demands of patients with cardiovascular diseases (CVD) on the primary care services is inevitably increased. However, the utilisation of primary care services across varying age groups is unknown. The study aims to explore age-related variations in provision of chronic disease management plans, mental health care, guideline-indicated cardiovascular medications and influenza vaccination among patients with CVD over differing ages presenting to primary care. Data for patients with CVD were extracted from 50 Australian general practices. Logistic regression, accounting for covariates and clustering effects by practices, was used for statistical analysis. Of the 14,602 patients with CVD (mean age, 72.5 years), patients aged 65-74, 75-84 and ≥85 years were significantly more likely to have a GP management plan prepared (adjusted odds ratio (aOR): 1.6, 1.88 and 1.55, respectively, p < 0.05), have a formal team care arrangement (aOR: 1.49, 1.8, 1.65, respectively, p < 0.05) and have a review of either (aOR: 1.63, 2.09, 1.93, respectively, p < 0.05) than those < 65 years. Patients aged ≥ 65 years were more likely to be prescribed blood-pressure-lowering medications and to be vaccinated for influenza. However, the adjusted odds of being prescribed lipid-lowering and antiplatelet medications and receiving mental health care were significantly lowest among patients ≥ 85 years. There are age-related variations in provision of primary care services and pharmacological therapy. GPs are targeting care plans to older people who are more likely to have long-term conditions and complex needs.

Data-driven quality improvement program to prevent hospitalisation and improve care of people living with coronary heart disease: Protocol for a process evaluation.

BACKGROUND: Practice-level quality improvement initiatives using rapidly advancing technology offers a multidimensional approach to reduce cardiovascular disease burden. For the "QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease" (QUEL) cluster randomised controlled trial, a 12-month quality improvement intervention was designed for primary care practices to use data and implement progressive changes using "Plan, Do, Study, Act" cycles within their practices with training in a series of interactive workshops. This protocol aims to describe the systematic methods to conduct a process evaluation of the data-driven intervention within the QUEL study. METHODS: A mixed-method approach will be used to conduct the evaluation. Quantitative data collected throughout the intervention period, via surveys and intervention materials, will be used to (1) identify the key elements of the intervention and how, for whom and in what context it was effective; (2) determine if the intervention is delivered as intended; and (3) describe practice engagement, commitment and capacity associated with various intervention components. Qualitative data, collected via semi-structured interviews and open-ended questions, will be used to gather in-depth understanding of the (1) satisfaction, utility, barriers and enablers; (2) acceptability, uptake and feasibility, and (3) effect of the COVID-19 pandemic on the implementation of the intervention. CONCLUSION: Findings from the evaluation will provide new knowledge on the implementation of a complex, multi-component intervention at practice-level using their own electronic patient data to enhance secondary prevention of cardiovascular disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134.

Pharmacist's time spent: Space for Pharmacy-based Interventions and Consultation TimE (SPICE)-an observational time and motion study.

OBJECTIVE: To describe the pharmacists' workflow, including tasks and time spent, to better understand their work capacity. DESIGN: Cross-sectional, observational, time and motion study. SETTING: Community pharmacies in Western Australia and New South Wales, Australia. PARTICIPANTS: Currently registered and practising pharmacists were approached using snowball sampling and selected using purposive techniques to obtain balance representation of metropolitan and rural pharmacies, as well as high and low script volumes where possible. RESULTS: Twenty-four pharmacists across 15 pharmacies participated during the 135 sessions totalling over 274 hours of observation. Dispensing (30%), indirect patient services (17%), counselling (15%) and professional management activities (15%) were the top four duties pharmacists performed, while only 2% of time was spent on professional services such as pain clinics and influenza vaccinations. Tasks were frequently interrupted and often performed simultaneously. Breaks and consumer-contact times were limited. More time was spent on professional service activities in non-metropolitan pharmacies, in pharmacies with greater daily prescription volumes and those with one or more support pharmacists. CONCLUSIONS: This is the first study to quantify the pharmacists' tasks in Australian community pharmacies. Much time is being spent on dispensing, supply and management activities with little time for providing additional professional services. An extra supporting pharmacist is likely necessary to increase professional services. These findings could support future research around barriers and enablers of conducive workflows and of extended professional services.

The impact of the Choosing Wisely Canada campaign on the simultaneous use of angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers: interrupted time-series analysis.

BACKGROUND: Choosing Wisely is a high-profile campaign seeking to reduce the use of low-value care. We investigated the impact of a Choosing Wisely Canada recommendation against using a combination of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for the management of hypertension, heart failure or diabetic nephropathy on population-level use of these medications in British Columbia, Canada. METHODS: We identified all people (any age) who were continuously registered with BC's Medical Service Plan between 2010 and 2017 with the targeted conditions. Using prescription claims data and an interrupted time-series analysis, we estimated the number of people on combination therapy per month, the proportion of days covered (PDC) by combination therapy per month and proportion of all combination prescriptions started per month in the 2 years before and after the introduction of the recommendation on Oct. 29, 2014. RESULTS: Of 1 104 593 people (mean age 65 yr, standard deviation 16 yr) in our study cohort, 4.6% were exposed to combination therapy, largely prescribed by family physicians (84%). The number of people on combination therapy and the PDC were declining before the recommendation, but the proportion of combination prescriptions started in the 2 years before the recommendation was increasing. After the recommendation, we observed no statistically significant changes in any outcome. The pre-existing downward trend of the monthly number of people decelerated (16.8, 95% confidence interval [CI] 14.0 to 19.5) and the proportion of prescriptions started increased (0.13%, 95% CI 0.08% to 0.18%). INTERPRETATION: The Choosing Wisely Canada recommendation against using a combination of ACE inhibitors and ARBs was not associated with reduced combination therapy use in the targeted conditions. The observed pre-existing declines in this practice questions the process of selecting recommendations, and the optimal implementation and value of Choosing Wisely campaigns without other reinforcing interventions.

Abortion Safety and Use with Normally Prescribed Mifepristone in Canada.

BACKGROUND: In the United States, mifepristone is available for medical abortion (for use with misoprostol) only with Risk Evaluation and Mitigation Strategy (REMS) restrictions, despite an absence of evidence to support such restrictions. Mifepristone has been available in Canada with a normal prescription since November 2017. METHODS: Using population-based administrative data from Ontario, Canada, we examined abortion use, safety, and effectiveness using an interrupted time-series analysis comparing trends in incidence before mifepristone was available (January 2012 through December 2016) with trends after its availability without restrictions (November 7, 2017, through March 15, 2020). RESULTS: A total of 195,183 abortions were performed before mifepristone was available and 84,032 after its availability without restrictions. After the availability of mifepristone with a normal prescription, the abortion rate continued to decline, although more slowly than was expected on the basis of trends before mifepristone had been available (adjusted risk difference in time-series analysis, 1.2 per 1000 female residents between 15 and 49 years of age; 95% confidence interval [CI], 1.1 to 1.4), whereas the percentage of abortions provided as medical procedures increased from 2.2% to 31.4% (adjusted risk difference, 28.8 percentage points; 95% CI, 28.0 to 29.7). There were no material changes between the period before mifepristone was available and the nonrestricted period in the incidence of severe adverse events (0.03% vs. 0.04%; adjusted risk difference, 0.01 percentage points; 95% CI, -0.06 to 0.03), complications (0.74% vs. 0.69%; adjusted risk difference, 0.06 percentage points; 95% CI, -0.07 to 0.18), or ectopic pregnancy detected after abortion (0.15% vs. 0.22%; adjusted risk difference, -0.03 percentage points; 95% CI, -0.19 to 0.09). There was a small increase in ongoing intrauterine pregnancy continuing to delivery (adjusted risk difference, 0.08 percentage points; 95% CI, 0.04 to 0.10). CONCLUSIONS: After mifepristone became available as a normal prescription, the abortion rate remained relatively stable, the proportion of abortions provided by medication increased rapidly, and adverse events and complications remained stable, as compared with the period when mifepristone was unavailable. (Funded by the Canadian Institutes of Health Research and the Women's Health Research Institute.).

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 Australia's limited capacity to contribute to the global effort in real-world studies of vaccine and disease-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.

Co-production of randomized clinical trials with patients: a case study in autologous hematopoietic stem cell transplant for patients with scleroderma.

BACKGROUND: Increasingly, it is argued that clinical trials struggle to recruit participants because they do not respond to key questions or study treatments that patients will be willing or able to use. This study explores how elicitation of patient-preferences can help designers of randomized controlled trials (RCTs) understand the impact of changing modifiable aspects of treatments or trial design on recruitment. METHODS: Focus groups and a discrete choice experiment (DCE) survey were used to elicit preferences of people with scleroderma for autologous hematopoietic stem cell transplant (AHSCT) treatment interventions. Preferences for seven attributes of treatment (effectiveness, immediate and long-term risk, care team composition and experience, cost, travel distance) were estimated using a mixed-logit model and used to predict participation in RCTs. RESULTS: Two hundred seventy-eight people with scleroderma answered the survey. All AHSCT treatment attributes significantly influenced preferences. Treatment effectiveness and risk of late complications contributed the most to participants' choices, but modifiable factors of distance to treatment center and cost also affected preferences. Predicted recruitment rates calibrated with participation in a recent trial (33%) and suggest offering a treatment closer to home, at lower patient cost, and with holistic, multidisciplinary care could increase participation to 51%. CONCLUSIONS: Through a patient engaged approach to preference elicitation for different features of AHSCT treatment options, we were able to predict what drives the decisions of people with scleroderma to participate in RCTs. Knowledge regarding concerns and the trade-offs people are willing to make can inform clinical study design, improving recruitment rates and potential uptake of the treatment of interest.

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.

Gender Comparison of Receipt of Government-Funded Health Services and Medication Prescriptions for the Management of Patients With Cardiovascular Disease in Primary Care.

BACKGROUND: Cardiovascular disease (CVD) and risk factors remains a major burden in terms of disease, disability, and death in the Australian population and mental health is considered as an important risk factor affecting cardiovascular disease. A multidisciplinary collaborative approach in primary care is required to ensure an optimal outcome for managing cardiovascular patients with mental health issues. Medicare introduced numerous primary care health services and medications that are subsidised by the Australian government in order to provide a more structured approach to reduce and manage CVD. However, the utilisation of these services nor gender comparison for CVD management in primary care has been explored. Therefore, the aim is to compare the provision of subsidised chronic disease management plans (CDMPs), mental health care and prescription of guideline-indicated medications to men and women with CVD in primary care practices for secondary prevention. METHODS: De-identified data for all active patients with CVD were extracted from 50 Australian primary care practices. Outcomes included the frequency of receipt of CDMPs, mental health care and prescription of evidence-based medications. Analyses adjusted for demography and clinical characteristics, stratified by gender, were performed using logistic regression and accounted for clustering effects by practices. RESULTS: Data for 14,601 patients with CVD (39.4% women) were collected. The odds of receiving the CDMPs was significantly greater amongst women than men (preparation of general practice management plan [GPMP]: (46% vs 43%; adjusted OR [95% CI]: 1.22 [1.12, 1.34]). Women were more likely to have diagnosed with mental health issues (32% vs 20%, p<0.0001), however, the adjusted odds of men and women receiving any government-subsidised mental health care were similar. Women were less often prescribed blood pressure, lipid-lowering and antiplatelet medications. After adjustment, only an antiplatelet medication or agent was less likely to be prescribed to women than men (44% vs 51%; adjusted OR [95% CI]: 0.84 [0.76, 0.94]). CONCLUSION: Women were more likely to receive CDMPs but less likely to receive antiplatelet medications than men, no gender difference was observed in the receipt of mental health care. However, the receipt of the CDMPs and the mental health treatment consultations were suboptimal and better use of these existing services could improve ongoing CVD management.

An electronic decision support-based complex intervention to improve management of cardiovascular risk in primary health care: a cluster randomised trial (INTEGRATE).

OBJECTIVES: To determine whether a multifaceted primary health care intervention better controlled cardiovascular disease (CVD) risk factors in patients with high risk of CVD than usual care. DESIGN, SETTING: Parallel arm, cluster randomised trial in 71 Australian general practices, 5 December 2016 - 13 September 2019. PARTICIPANTS: General practices that predominantly used an electronic medical record system compatible with the HealthTracker electronic decision support tool, and willing to implement all components of the INTEGRATE intervention. INTERVENTION: Electronic point-of-care decision support for general practices; combination cardiovascular medications (polypills); and a pharmacy-based medication adherence program. MAIN OUTCOME MEASURES: Proportion of patients with high CVD risk not on an optimal preventive medication regimen at baseline who had achieved both blood pressure and low-density lipoprotein (LDL) cholesterol goals at study end. RESULTS: After a median 15 months' follow-up, primary outcome data were available for 4477 of 7165 patients in the primary outcome cohort (62%). The proportion of patients who achieved both treatment targets was similar in the intervention (423 of 2156; 19.6%) and control groups (466 of 2321; 20.1%; relative risk, 1.06; 95% CI, 0.85-1.32). Further, no statistically significant differences were found for a number of secondary outcomes, including risk factor screening, preventive medication prescribing, and risk factor levels. Use of intervention components was low; it was highest for HealthTracker, used at least once for 347 of 3236 undertreated patients with high CVD risk (10.7%). CONCLUSIONS: Despite evidence for the efficacy of its individual components, the INTEGRATE intervention was not broadly implemented and did not improve CVD risk management in participating Australian general practices. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000233426 (prospective).

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.

The Medicines Intelligence Centre of Research Excellence: Co-creating real-world evidence to support the evidentiary needs of Australian medicines regulators and payers.

Regulators and payers play a pivotal role in facilitating timely and affordable access to safe and efficacious medicines. They use evidence generated from randomised clinical trials (RCTs) to support decisions to register and subsidise medicines. However, at the time of registration and subsidy approval, regulators and payers face uncertainty about how RCT outcomes will translate to real-world clinical practice. In response to this situation, medicines policy agencies worldwide have endorsed the use of real-world data (RWD) to derive novel insights on the use and outcomes of prescribed medicines. Recent reforms around data availability and use in Australia are creating unparalleled data access and opportunities for Australian researchers to undertake large-scale research to generate evidence on the safety and effectiveness of medicines in the real world. Highlighting the critical importance of research in this area, Quality Use of Medicines and Medicine Safety was announced as Australia's 10th National Health Priority in 2019. The National Health and Medical Research Council, Medicines Intelligence Centre of Research Excellence (MI-CRE) has been formed to take advantage of the renewed focus on quality use of medicines and the changing data landscape in Australia. It will generate timely research supporting the evidentiary needs of Australian medicines regulators and payers by accelerating the development and translation of real-world evidence on medicines use and outcomes. MI-CRE is developing a coordinated approach to identify, triage and respond to priority questions where there are significant uncertainties about medicines use, (cost)-effectiveness, and/or safety and creating a data ecosystem that will streamline access to Australian data to enable researchers to generate robust evidence in a timely manner. This paper outlines how MI-CRE will partner with policy makers, clinicians, and consumer advocates to leverage real-world data to co-create real-world evidence, to improve quality use of medicines and reduce medicine-related harm.

Out-of-pocket spending among a cohort of Australians living with gout.

OBJECTIVE: To measure the direct and indirect out-of-pocket (OOP) costs borne by Australians with gout. METHODS: A cross-sectional, Australia-wide, web-based survey was conducted over 12 months between May 2017 and April 2018. Participants were recruited via advertisements in doctors' clinics and healthcare organizations' websites, and social media platforms such as Facebook and Twitter. Survey questions collected information about participants' OOP spending on direct medical and non-medical gout-related healthcare costs. Participant demographics, gout status, healthcare sought, workdays lost to due gout and health-related quality of life were also collected. RESULTS: Seventy-nine patients with gout completed the survey; 70 (89%) were male, and on average were 56 (SD 16) years of age and had gout for 14 (SD 12) years. For this cohort, the median total OOP direct medical cost was AU$200 per year (interquartile range [IQR]: AU$60-AU$570). Sixty (76%) people with gout reported being affected by gout during work; however, only 0.25 (IQR: 0-3) days of work (approximately $60) were lost due to gout in a year. Nine percent (n = 7) of participants experienced cost-related treatment attrition and 33% reported economic hardship (n = 26). Participants who experienced economic hardship or cost-related treatment attrition had higher median total gout-related direct costs than those who did not. CONCLUSION: In Australia, gout has an OOP financial cost and reduces work productivity. The presence of cost-related treatment attrition among people with gout indicates that financial costs may be a significant barrier to seeking treatment for a subset of patients with gout.

Designing Discrete Choice Experiments Using a Patient-Oriented Approach.

Patient-oriented research is a process whereby patients or caregivers are included as research partners so that research focusses on topics that are priorities and lead to findings that translate into practice. Using a case study of preferences for stem cell transplant in scleroderma, we report on a patient-oriented research approach to developing a discrete choice experiment. Our patient-oriented research application followed the four guiding principles in Canada's Strategy for Patient-Oriented Research: inclusiveness, support, mutual respect and co-build. In this case study, patient partners were involved at different levels of engagement to match individual availability, skillset and roles in the team. They advised, to different degrees, on all aspects of the study from design to analyses. Using a patient-oriented research approach led to the inclusion of attributes that would likely have been excluded (e.g. support from a multidisciplinary team), and realistic framing of patient-relevant and sometimes sensitive attributes (e.g. mortality and cost). Meeting locations and times were adjusted to accommodate all-team circumstances. Institutional constraints on the reimbursement for patient partners influenced the timing and extent of involvement. We found that adopting a patient-oriented research approach to discrete choice experiment design injected unique knowledge and expertise into the team, improved the representativeness of the sample recruited, minimised researcher biases, and ensured appropriate attribute selection and descriptions. The patient-oriented research approach highlighted some constraints of discrete choice experiment designs and, while not a solution, might ensure the methodological trade-offs remain patient relevant. Institutional challenges must be addressed to progress patient-oriented health economics research.