Guidelines for genetic testing in prostate cancer: a scoping review.

BACKGROUND: Genetic testing, to identify pathogenic or likely pathogenic variants in prostate cancer, is valuable in guiding treatment decisions for men with prostate cancer and to inform cancer prevention and early detection options for their immediate blood relatives. There are various guidelines and consensus statements for genetic testing in prostate cancer. Our aim is to review genetic testing recommendations across current guidelines and consensus statements and the level of evidence supporting those recommendations. METHODS: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) guidelines. Electronic database searches and manual searches of grey literature, including websites of key organisations were conducted. Using the Population, Concept, Context (PCC) framework, this scoping review included: men with prostate cancer or men at high risk of prostate cancer and their biological families; existing guidelines and consensus statements with supporting evidence for genetic testing of men with prostate cancer from any geographical location worldwide. RESULTS: Of the 660 citations identified, 23 guidelines and consensus statements met the inclusion criteria for the scoping review. Based on different levels of evidence about who should be tested and how, a diverse range of recommendations were identified. There was general consensus among the guidelines and consensus statements that men with metastatic disease be offered genetic testing; however, there was less consensus in relation to genetic testing in localised prostate cancer. While there was some consensus in relation to which genes to test, recommendations varied regarding who to test, testing methods and implementation. CONCLUSION: While genetic testing in prostate cancer is routinely recommended and numerous guidelines exist, there is still considerable lack of consensus regarding who should be tested and how they should be tested. Further evidence is needed to inform value-based genetic testing strategies for implementation in practice.

A Benefit-Cost Analysis of BackTrack, a Multi-Component, Community-Based Intervention for High-Risk Young People in a Rural Australian Setting.

BackTrack is a multi-component, community-based program designed to build capacity amongst high-risk young people. The aim of this study was to conduct a benefit-cost analysis of BackTrack, which was implemented in Armidale, a rural town in New South Wales, Australia. Costs and benefits were identified, measured and valued in 2016 Australian dollars. Costs were estimated from program financial and administrative records. Benefits were estimated using a pre-post design and conservative economic assumptions. Benefits included education attendance or completion; employment; engagement with health service providers; reduced homelessness; economic productivity; reduced vandalism to local infrastructure; reduced youth crime; reduced engagement with the justice system; and program income generated by participants. The counterfactual baseline was zero educational outcome, based on discussions with BackTrack staff and expert informants. We tested this assumption compared to the assumption that participants had a Year 8 education. There was evidence of significant quantifiable improvements in several outcomes: high school attendance or completion, vocational education attendance or completion, unskilled or vocationally qualified employment and economic productivity. Reduced homelessness, engagement with health services and acquisition of job readiness skills, as well as reduced local infrastructure vandalism and reduced crime were further quantifiable improvements. The net social benefit of BackTrack was estimated at $3,267,967 with a benefit-cost ratio of 2.03, meaning that every dollar invested in BackTrack would return $2.03 in benefits. BackTrack represents a viable funding option for a government interested in addressing the needs of high-risk young people.

Exercise in preventing falls for men with prostate cancer: a modelled cost-utility analysis.

INTRODUCTION: Men who receive androgen deprivation therapy (ADT) for prostate cancer (PCa) are a vulnerable falls population due to the side effects of treatment. The purpose of this paper is to determine the cost-effectiveness of exercise in preventing falls and fractures for this high-risk population in Australia. METHODS: A decision analytic model was constructed to evaluate the cost utility of an exercise intervention compared to usual care from a health system perspective. The intervention comprised two 1-h sessions of supervised exercise per week over 1 year for men with non-metastatic PCa receiving curative radiation therapy and ADT. A Markov model simulated the transition between five health states: (1) at risk of falling; (2) at recurrent risk of falling; (3) fracture (minor or major); (4) non-fracture injury (minor or major); and (5) death. Model inputs including transition probabilities and utility scores were obtained from published meta-analyses, and costs were drawn from Australian data sources (e.g. Medical Benefits Schedule). The model time horizon was 3 years, and costs and effects were discounted at 5% annual rate. Costs and quality-adjusted life years (QALYs) were aggregated and compared between the intervention and control to calculate incremental net monetary benefit (iNMB). Uncertainty in the results was explored using deterministic and probabilistic sensitivity analyses (PSA). RESULTS: At a willingness-to-pay of AU$50,000 per QALY, the exercise intervention dominated, as it was less costly and more effective than usual care. The iNMB was $3010 per patient. The PSA showed a 58% probability the intervention was cost-effective. CONCLUSION: This is the first modelled economic evaluation of exercise for men with PCa. Our results suggest supervised exercise is cost-effective in reducing the risks of falls and fractures in this population.

Exploring Community-Based Options for Reducing Youth Crime.

BackTrack is a multi-component, community-based intervention designed to build capacity amongst 14-17-year-old high risk young people. The aim of the current study seeks to explore community value and preferences for reducing youth crime and improving community safety using BackTrack in a rural setting in Armidale, New South Wales, Australia. The study design used discrete choice experiments (DCEs), designed in accordance with the 10-item checklist outlined by the International Society for Pharmacoeconomics and Outcomes Research. The DCE was pilot tested on 43 participants to test feasibility and comprehension. A revised version of the survey was subsequently completed by 282 people over a 12-day period between 30 May 2016 and 10 June 2016, representing a survey response rate of 35%. Ninety per cent of respondents were residents of Armidale, the local rural town where BackTrack was implemented. The DCE generated results that consistently demonstrated a preference for social programs to address youth crime and community safety in the Armidale area. Respondents chose BackTrack over Greater Police Presence 75% of the time with an annual benefit of Australian dollars (AUD) 150 per household, equivalent to a community benefit of AUD 2.04 million. This study estimates a strong community preference for BackTrack relative to more policing (a community willing to pay equivalent to AUD 2.04 million) highlighting the clear value of including community preferences when evaluating community-based programs for high-risk young people.

Economic evaluation of a web-based menu planning intervention to improve childcare service adherence with dietary guidelines.

BACKGROUND: Despite the known benefits of healthy eating in childhood, few Australian childcare services provide food that is consistent with dietary guidelines. The effectiveness of a web-based menu planning intervention to increase childcare service provision of healthy foods and decrease provision of discretionary foods in long day-care services in Australia was assessed in a randomised controlled trial. Here we consider the costs, consequences, cost-effectiveness and budget impact of the intervention using data collected within the trial. METHODS: The prospective trial-based economic evaluation involved 54 childcare services across New South Wales (NSW), Australia. Services were randomised to a 12-month intervention or usual care. The intervention involved access to a web-based menu planning and decision support tool and online resources. Effectiveness measures included mean number of food groups, overall menu and individual food group compliance with dietary guidelines, and mean servings of food groups at 12 months. Costs (reported in $AUD, 2017/18) were evaluated from both health sector and societal perspectives. The direct cost to support uptake of the intervention was calculated, as were costs to each childcare service. The incremental cost of the intervention was calculated as the net difference in the cost to undertake menu planning and review plus the direct cost of the intervention. Incremental cost-effectiveness ratios (ICERs) including uncertainty intervals were estimated for differences in costs and effects between intervention and control groups. A relative value index was calculated to determine overall value for money. RESULTS: Over the 12 months of the trial, we calculated a difference in cost between usual practice and intervention groups of - $482 (95% UI - $859, - $56). While the measured increase in menu and food group compliance within the trial did not reach statistical significance, there were significant improvements in mean servings of fruit and discretionary food, represented in the cost-consequence analysis. The calculated relative value index of 1.1 suggests that the intervention returns acceptable value for money for the outcomes generated. CONCLUSION: Compared to usual practice, web-based programmes may offer an efficient and sustainable alternative for childcare services to improve the provision of healthy foods to children in their care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616000974404.

The role of exercise in the management of adverse effects of androgen deprivation therapy for prostate cancer: a rapid review.

PURPOSE: Prostate cancer (PCa) is the most commonly diagnosed cancer in Australia, accounting for one quarter of all new cancer diagnoses for males. Androgen deprivation therapy (ADT) is the standard first-line therapy for metastatic PCa but is also used across much of the spectrum of disease. Unfortunately, debilitating adverse effects are a significant and largely unavoidable feature of ADT. A recent systematic review of adverse effects of ADT identified 19 sub-groups classified according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The potential for multiple simultaneous adverse effects, their associated management and the impact of adverse effects on cancer outcomes and quality of life are important considerations in the treatment and supportive care of men with PCa. Exercise is increasingly being recognized as an efficacious strategy in managing these adverse effects. METHODS: A rapid review was undertaken to examine the role of exercise in the management of the most commonly reported ADT adverse effects classified according to the CTCAE sub-groups. A systematic search was conducted in Medline, PsycINFO, Google Scholar and Google for the years 2010 to September 2019 to identify the benefits of exercise in managing the adverse effects of ADT for PCa. RESULTS: There is strong evidence for exercise as medicine in addressing several of the adverse effects of PCa such as loss of muscle mass and strength, fatigue and declining physical function. Moderate level evidence for PCa exists for exercise-induced improvements in depression and anxiety, bone loss, and sexual dysfunction. While evidence of the effectiveness of exercise is lacking for many adverse effects of ADT for PCa, evidence in the cancer population as a whole or other clinical populations is strong, and many clinical guidelines recommend exercise as a fundamental part of their clinical management. With the exception of gynaecomastia and breast pain, there is increasing evidence (PCa, cancer or other clinical populations) to suggest that exercise has the potential to reduce and even prevent many of the adverse effects of ADT, thus improving survivorship outcomes for men with PCa. CONCLUSION: Exercise has the potential to reduce and even prevent many of the adverse effects of ADT, thus improving survivorship outcomes for men with PCa. The use of exercise for PCa management has the potential to translate into health and economic benefits in improved quality of life and fewer complications, resulting in savings to the health care system, enhanced productivity and reduced patient and carer burden. Exercise thus has the potential to improve quality of life for this population as well as generate significant cost savings.

Cost-Effectiveness Analysis of Supervised Exercise Training in Men with Prostate Cancer Previously Treated with Radiation Therapy and Androgen-Deprivation Therapy.

BACKGROUND: Exercise for prostate cancer (PCa) survivors has been shown to be effective in addressing metabolic function and associated co-morbidities, as well as sarcopenia and significant functional impairment resulting from long-term androgen deprivation. Evidence on the cost-effectiveness of exercise interventions for PCa, however, is lacking, thus the aim of this study was to determine the cost-effectiveness of a supervised exercise intervention for long-term PCa survivors who previously received radiation therapy and androgen-deprivation therapy. METHODS: Cost-effectiveness analysis from an Australian healthcare-payer perspective was conducted using patient-level data from a multicentre randomised controlled trial (RCT) of supervised exercise training (resistance and aerobic) compared to receiving printed exercise material and a recommendation to exercise in long-term PCa survivors (> 5 years post-diagnosis). Analysis was undertaken for the 6-month supervised exercise portion of the intervention, which involved 100 men aged between 62 and 85 years, 50 in each arm. The primary outcome was cost per quality-adjusted life-years (QALYs). RESULTS: A 6-month supervised exercise intervention for PCa survivors resulted in an incremental cost-effectiveness ratio of AU$64,235 (2018 AUD) at an incremental cost of AU$546 per person and a QALY gain of 0.0085. At a willingness-to-pay of AU$50,000, the probability that the intervention is cost-effective was 41%. Sensitivity analysis showed that maintenance of benefits via a 6-month home-based intervention, immediately following the supervised intervention, lowered the cost per QALY gained to AU$32,051. DISCUSSION: This is the first cost-effectiveness analysis of exercise for PCa survivors. The intervention was effective, but unlikely to be cost-effective at the generally accepted willingness-to-pay of AU$50,000 per QALY. It is likely that evidence to support cost savings from post-intervention outcomes would reveal greater benefits and contribute to a more comprehensive cost-effectiveness analysis. Future RCTs should incorporate longer follow-up durations and collection of data to support modelling to capture future health benefits. Measures of quality of life or utility more sensitive to the impact of physical activity would also improve future economic evaluations.

Incidence of the adverse effects of androgen deprivation therapy for prostate cancer: a systematic literature review.

PURPOSE: Androgen deprivation therapy (ADT) has broad application in the treatment of prostate cancer (PC) and is associated with numerous, debilitating adverse effects. Increasing use of ADT for PC, longer timeframe for treatment (increased uptake of PSA testing and earlier diagnosis), as well as improved survival and an ageing population, means patients can live for a considerable period of time on or after ADT, experiencing these adverse effects. A number of systematic reviews of adverse effects of ADT for PC exist; however, no single systematic review has previously examined the evidence for all adverse effects, including newer forms of ADT. METHODS: A systematic review of existing systematic reviews of ADT for PC was conducted (2010-February 2019), as per Cochrane guidelines, to identify the highest level of risk/incidence evidence available, supplemented by evidence drawn from individual studies where no systematic review existed. RESULTS: Incidence data was generated for 19 adverse effect subgroups, classified according to the common terminology criteria for adverse events (CTCAE). CONCLUSION: Incidence of adverse effects provides valuable information for future burden of disease studies. This information can better guide clinical management to reduce symptoms for patients and assist patients to make more informed decisions about their treatment, potentially improving disease outcomes. It also highlights the importance of supportive care for PC patients receiving ADT and their carers. For analysts conducting economic evaluations, the inclusion of adverse effects in PC decision analytic models can provide more comprehensive and accurate information for decision makers.

Comparison of Potentially Inappropriate Medications for People with Dementia at Admission and Discharge during An Unplanned Admission to Hospital: Results from the SMS Dementia Study.

People with dementia (PWD) and cognitive impairment are particularly vulnerable to medication problems, and unplanned admission to hospital presents an opportunity to address polypharmacy, potentially inappropriate medications (PIMs) and anticholinergic burden. This study aimed to compare PIMS and other medication data for PWD to determine whether these changed during hospitalization. Medications documented in patient's records at admission and discharge were evaluated for PWD recruited to phase one of a prospective quasi-experimental pre/post-controlled trial that was conducted at two regional hospitals in NSW, Australia. The study sample included PWD or cognitive impairment having an unplanned admission to hospital. Data were collected using a purpose developed audit tool for medications and PIMs, and a Modified Anticholinergic Burden Scale. Total participants were 277, and results determined that the cognitive status of PWD is not always detected during an unplanned admission. This may make them more vulnerable to medication problems and poor outcomes. Polypharmacy and PIMS for PWD were high at admission and significantly reduced at discharge. However, PWD should be routinely identified as high risk at admission; and there is potential to further reduce polypharmacy and PIMs during admission to hospital, particularly psychotropic medications at discharge. Future studies should focus on evaluating targeted interventions designed to increase medication safety for PWD.

Cost-effectiveness of targeted thrombolytic therapy for stroke patients using multi-modal CT compared to usual practice.

INTRODUCTION: The use of multimodal computed tomography imaging (MMCT) in routine clinical assessment of stroke patients improves the identification of patients with large regions of salvageable brain tissue, lower risk for haemorrhagic transformation, or a large vessel occlusion requiring endovascular therapy. AIM: To evaluate the cost-effectiveness of using MMCT compared to usual practice for determining eligibility for reperfusion therapy with alteplase using real world data from the International Stroke Perfusion Imaging Registry (INSPIRE). METHODS: We performed a cost-utility analysis. Mean costs and quality-adjusted life years (QALYs) per patient for two alternative screening protocols were calculated. Protocol 1 represented usual practice, while Protocol 2 reflected treatment targeting using multimodal imaging. Cost-effectiveness was assessed using the net-benefit framework. RESULTS: Protocol 1 had a total mean per patient cost of $2,013 USD and 0.148 QALYs. Protocol 2 had a total mean per patient cost of $1,519 USD and 0.153 QALYs. For a range of willingness-to-pay values, representing implicit thresholds of cost-effectiveness, the lower bound of the incremental net monetary benefit statistic was consistently greater than zero, indicating that MMCT is cost- effective compared to usual practice. The results were most sensitive to variation in the mean number of alteplase vials administered. CONCLUSION: In a healthcare setting where multimodal imaging technologies are available and reimbursed, their use in screening patients presenting with acute stroke to determine eligibility for alteplase treatment is cost-effective given a range of willingness-to-pay thresholds and warrants consideration as an alternative to routine practice.

Systematic review of economic evaluations of interventions for high risk young people.

BACKGROUND: The aim of this systematic literature review is to identify and critique full economic evaluations of interventions for high risk young people with the purpose of informing the design of future rigorous economic evaluations of such intervention programs. METHODS: A PRISMA compliant search of the literature between 2000 and April 2018 was conducted to identify full economic evaluations of youth focussed interventions for at risk young people. Duplicates were removed and two researchers independently screened the article titles and abstracts according to PICOS criteria for exclusion and inclusion. The remaining full text articles were assessed for eligibility and a quality assessment of the included articles was conducted using the Drummond checklist. RESULTS: The database, grey literature and hand searches located 488 studies of interventions for at risk young people. After preliminary screening of titles and abstracts, 104 studies remained for full text examination and 29 empirical studies containing 32 separate economic evaluations were judged eligible for inclusion in the review. These comprised 13 cost-benefit analyses (41%), 17 cost-effectiveness analyses (53%), one cost-utility analysis (3%) and a social return on investment (3%). Three main methodological challenges were identified: 1. attribution of effects; 2. measuring and valuing outcomes; and 3. identifying relevant costs and consequences. CONCLUSIONS: A cost-benefit analysis would best capture the dynamic nature of a multi-component intervention for high risk young people, incorporating broader intersectoral outcomes and enabling measurement of more domains of risk. Prospective long-term data collection and a strong study design that incorporates a control group contribute to the quality of economic evaluation. Extrapolation of impact into the future is important for this population, in order to account for the time lag in effect of many impacts and benefits arising from youth interventions.

Apunipima baby basket program: a retrospective cost study.

BACKGROUND: The Baby Basket initiative was developed by Apunipima Cape York Health Council (ACYHC) to address poor maternal and child health (MCH) in Cape York, the northernmost region of Queensland. While positive outcomes for Indigenous MCH programs are reported in the literature, few studies have a strong evidence base or employ a sound methodological approach to evaluation. The aim of the cost study is to identify the resources required to deliver the Baby Basket program in the remote communities of Cape York. It represents an initial step in the economic evaluation of the Apunipima Baby Basket program. The aim of this study was to report whether the current program represents an effective use of scarce resources. METHOD: The cost study was conducted from the perspective of the health providers and reflects the direct resources required to deliver the Baby Basket program to 170 women across 11 communities represented by ACYHC. A flow diagram informed by interviews with ACYHC staff, administrative documents and survey feedback was used to map the program pathway and measure resource use. Monetary values, in 2013 Australian dollars, were applied to the resources used to deliver the Baby Basket program for one year. RESULTS: The total cost of delivering the Baby Basket progam to 170 participants in Cape York was $148,642 or approximately, $874 per participant. The analysis allowed for the cost of providing the Baby Baskets to remote locations and the time for health workers to engage with women and thereby encourage a relationship with the health service. Routinely collected data showed improved engagement between expectant women and the health service during the life of the program. CONCLUSION: The Apunipima Baby Basket cost study identifies the resources required to deliver this program in remote communities of Cape York and provides a framework that will support prospective data collection of more specific outcome data, for future cost-effectiveness analyses and cost-benefit analyses. An investment of $874 per Baby Basket participant was associated with improved engagement with the health service, an important factor in maternal and child health.

An approach to measuring and encouraging research translation and research impact.

BACKGROUND: Research translation, particularly in the biomedical area, is often discussed but there are few methods that are routinely used to measure it or its impact. Of the impact measurement methods that are used, most aim to provide accountability - to measure and explain what was generated as a consequence of funding research. This case study reports on the development of a novel, conceptual framework that goes beyond measurement. The Framework To Assess the Impact from Translational health research, or FAIT, is a platform designed to prospectively measure and encourage research translation and research impact. A key assumption underpinning FAIT is that research translation is a prerequisite for research impact. METHODS: The research impact literature was mined to understand the range of existing frameworks and techniques employed to measure and encourage research translation and research impact. This review provided insights for the development of a FAIT prototype. A Steering Committee oversaw the project and provided the feedback that was used to refine FAIT. RESULTS: The outcome of the case study was the conceptual framework, FAIT, which is based on a modified program logic model and a hybrid of three proven methodologies for measuring research impact, namely a modified Payback method, social return on investment, and case studies or narratives of the process by which research translates and generates impact. CONCLUSION: As funders increasingly seek to understand the return on their research investments, the routine measurement of research translation and research impact is likely to become mandatory rather than optional. Measurement of research impact on its own is insufficient. There should also be a mechanism attached to measurement that encourages research translation and impact - FAIT was designed for this task.