Preventing chronic disease in overweight and obese patients with low health literacy using eHealth and teamwork in primary healthcare (HeLP-GP): a cluster randomised controlled trial.

OBJECTIVES: To evaluate a multifaceted intervention on diet, physical activity and health literacy of overweight and obese patients attending primary care. DESIGN: A pragmatic two-arm cluster randomised controlled trial. SETTING: Urban general practices in lower socioeconomic areas in Sydney and Adelaide. PARTICIPANTS: We aimed to recruit 800 patients in each arm. Baseline assessment was completed by 215 patients (120 intervention and 95 control). INTERVENTION: A practice nurse-led preventive health check, a mobile application and telephone coaching. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were measured at baseline, 6 and 12 months, and included patient health and eHealth literacy, weight, waist circumference and blood pressure. Secondary outcomes included changes in diet and physical activity, preventive advice and referral, blood lipids, quality of life and costs. Univariate and multivariate analyses of difference-in-differences (DiD) estimates for each outcome were conducted. RESULTS: At 6 months, the intervention group, compared with the control group, demonstrated a greater increase in Health Literacy Questionnaire domain 8 score (ability to find good health information; mean DiD 0.22; 95% CI 0.01 to 0.44). There were similar differences for domain 9 score (understanding health information well enough to know what to do) among patients below the median at baseline. Differences were reduced and non-statistically significant at 12 months. There was a small improvement in diet scores at 6 months (DiD 0.78 (0.10 to 1.47); p=0.026) but not at 12 months. There were no differences in eHealth literacy, physical activity scores, body mass index, weight, waist circumference or blood pressure. CONCLUSIONS: Targeted recruitment and engagement were challenging in this population. While the intervention was associated with some improvements in health literacy and diet, substantial differences in other outcomes were not observed. More intensive interventions and using codesign strategies to engage the practices earlier may produce a different result. Codesign may also be valuable when targeting lower socioeconomic populations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN 12617001508369) (http://www.ANZCTR.org.au/ACTRN12617001508369.aspx). TRIAL PROTOCOL: The protocol for this trial has been published (open access; https://bmjopen.bmj.com/content/8/6/e023239).

Taking the pulse of the health services research community: a cross-sectional survey of research impact, barriers and support.

Objective This study reports on the characteristics of individuals conducting health service research (HSR) in Australia and New Zealand, the perceived accessibility of resources for HSR, the self-reported impact of HSR projects and perceived barriers to conducting HSR. Methods A sampling frame was compiled from funding announcements, trial registers and HSR organisation membership. Listed researchers were invited to complete online surveys. Close-ended survey items were analysed using basic descriptive statistics. Goodness of fit tests determined potential associations between researcher affiliation and access to resources for HSR. Open-ended survey items were analysed using thematic analysis. Results In all, 424 researchers participated in the study (22% response rate). Respondents held roles as health service researchers (76%), educators (34%) and health professionals (19%). Most were employed by a university (64%), and 57% held a permanent contract. Although 63% reported network support for HSR, smaller proportions reported executive (48%) or financial (26%) support. The least accessible resources were economists (52%), consumers (49%) and practice change experts (34%); researchers affiliated with health services were less likely to report access to statisticians (P<0.001), economists (P<0.001), librarians (P=0.02) and practice change experts (P=0.02) than university-affiliated researchers. Common impacts included conference presentations (94%), publication of peer-reviewed articles (87%) and health professional benefits (77%). Qualitative data emphasised barriers such as embedding research culture within services and engaging with policy makers. Conclusions The data highlight opportunities to sustain the HSR community through dedicated funding, improved access to methodological expertise and greater engagement with end-users. What is known about the topic? HSR faces several challenges, such as inequitable funding allocation and difficulties in quantifying the effects of HSR on changing health policy or practice. What does this paper add? Despite a vibrant and experienced HSR community, this study highlights some key barriers to realising a greater effect on the health and well-being of Australian and New Zealand communities through HSR. These barriers include limited financial resources, methodological expertise, organisational support and opportunities to engage with potential collaborators. What are the implications for practitioners? Funding is required to develop HSR infrastructure, support collaboration between health services and universities and combine knowledge of the system with research experience and expertise. Formal training programs for health service staff and researchers, from short courses to PhD programs, will support broader interest and involvement in HSR.

Supporting surgeons in patient-centred complex decision-making: a qualitative analysis of the impact of a perioperative physician clinic.

OBJECTIVE: Patients with comorbidities can be referred to a physician-led high-risk clinic for medical optimisation prior to elective surgery at the discretion of the surgical consultant, but the factors that influence this referral are not well understood. The aims of this study were to understand the factors that influence a surgeon's decision to refer a patient to the clinic, and how the clinic impacts on the management of complex patients. DESIGN: Qualitative study using theoretical thematic analysis to analyse transcribed semi-structured interviews. SETTING: Interviews were held in either the surgical consultant's private office or a quiet office/room in the hospital ward. PARTICIPANTS: Seven surgical consultants who were eligible to refer patients to the clinic. RESULTS: When discussing the factors that influence a referral to the clinic, all participants initially described the optimisation of comorbidities and would then discuss with examples the challenges with managing complex patients and communicating the risks involved with having surgery. When discussing the role of the clinic, two related subthemes were dominant and focused on the management of risk in complex patients. The participants valued the involvement of the clinic in the decision-making and communication of risks to the patient. CONCLUSIONS: The integration of the high-risk clinic in this study appears to offer additional value in supporting the decision-making process for the surgical team and patient beyond the clinical outcomes. The factors that influence a surgeon's decision to refer a patient to the clinic appear to be driven by the aim to manage the uncertainty and risk to the patient regarding surgery and it was seen as a strategy for managing difficult and complex cases.

Preventing chronic disease in patients with low health literacy using eHealth and teamwork in primary healthcare: protocol for a cluster randomised controlled trial.

INTRODUCTION: Adults with lower levels of health literacy are less likely to engage in health-promoting behaviours. Our trial evaluates the impacts and outcomes of a mobile health-enhanced preventive intervention in primary care for people who are overweight or obese. METHODS AND ANALYSIS: A two-arm pragmatic practice-level cluster randomised trial will be conducted in 40 practices in low socioeconomic areas in Sydney and Adelaide, Australia. Forty patients aged 40-70 years with a body mass index ≥28 kg/m2 will be enrolled per practice. The HeLP-general practitioner (GP) intervention includes a practice-level quality improvement intervention (medical record audit and feedback, staff training and practice facilitation visits) to support practices to implement the clinical intervention for patients. The clinical intervention involves a health check visit with a practice nurse based on the 5As framework (assess, advise, agree, assist and arrange), the use of a purpose-built patient-facing app, my snapp, and referral for telephone coaching. The primary outcomes are change in health literacy, lifestyle behaviours, weight, waist circumference and blood pressure. The study will also evaluate changes in quality of life and health service use to determine the cost-effectiveness of the intervention and examine the experiences of practices in implementing the programme. ETHICS AND DISSEMINATION: The study has been approved by the University of New South Wales (UNSW) Human Research Ethics Committee (HC17474) and ratified by the University of Adelaide Human Research Ethics committee. There are no restrictions on publication, and findings of the study will be made available to the public via the Centre for Primary Health Care and Equity website and through conference presentations and research publications. Deidentified data and meta-data will be stored in a repository at UNSW and made available subject to ethics committee approval. TRIAL REGISTRATIONREGISTRATION NUMBER: ACTRN12617001508369; Pre-results.

A randomized trial of a 1-hour troponin T protocol in suspected acute coronary syndromes: Design of the Rapid Assessment of Possible ACS In the emergency Department with high sensitivity Troponin T (RAPID-TnT) study.

BACKGROUND: Protocols incorporating high-sensitivity troponin to guide decision making in the disposition of patients with suspected acute coronary syndromes (ACS) in the emergency department have received a lot of attention. Traditionally, patients with chest pain have required long periods of observation in emergency department before being deemed safe for discharge. In an era of limited health service resources, a protocol that could discharge patients safely within an hour of presentation is extremely attractive. Unfortunately, despite incorporation into some guidelines, these protocols have not been subjected to randomized comparisons evaluating safety, effectiveness, and cost-effectiveness. OBJECTIVE: This study is designed to provide the evidence required to allow key decision makers to implement these protocols: specifically, to provide evidence that a decision rule based on 0- and 1-hour high-sensitivity troponin T (hs-TnT) is safe, provides noninferior outcomes in all patients with suspected ACS, and that implementation of a rapid troponin protocol leads to efficient care. DESIGN: This prospective pragmatic trial (n=5,400, 5 hospitals) randomly allocates patients with suspected ACS to either a 0/1-hour hs-TnT protocol as advocated in clinical guidelines, versus usual care of standard troponin reporting evaluated at 3 and 6hours. The primary effectiveness composite end points of this study are all-cause death and new/recurrent ACS within 30days. To evaluate cost-effectiveness, follow-up will determine clinical events, quality of life, and resource utilization within 12 months. SUMMARY: Demonstrating that a 0/1-hour hs-TnT protocol improves the effectiveness and efficiency of care within a robust comparative study will fill an evidence gap that currently limits the translation of more precise hs-TnT testing into better patient and health service outcomes.

Cost-effectiveness of lapatinib plus capecitabine in women with HER2+ metastatic breast cancer who have received prior therapy with trastuzumab.

BACKGROUND: In a phase III trial of women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab, an anthracycline, and taxanes (EGF100151), lapatinib plus capecitabine (L+C) improved time to progression (TTP) versus capecitabine monotherapy (C-only). In a trial including HER2+ MBC patients who had received at least one prior course of trastuzumab and no more than one prior course of palliative chemotherapy (GBG 26/BIG 03-05), continued trastuzumab plus capecitabine (T+C) also improved TTP. METHODS: An economic model using patient-level data from EGF100151 and published results of GBG 26/BIG 03-05 as well as other literature were used to evaluate the incremental cost per quality-adjusted life-year [QALY] gained with L+C versus C-only and versus T+C in women with HER2+ MBC previously treated with trastuzumab from the UK National Health Service (NHS) perspective. RESULTS: Expected costs were £28,816 with L+C, £13,985 with C-only and £28,924 with T+C. Corresponding QALYs were 0.927, 0.737 and 0.896. In the base case, L+C was estimated to provide more QALYs at a lower cost compared with T+C; cost per QALY gained was £77,993 with L+C versus C-only. In pairwise probabilistic sensitivity analyses, the probability that L+C is preferred to C-only was 0.03 given a threshold of £30,000. The probability that L+C is preferred to T+C was 0.54 regardless of the threshold. CONCLUSIONS: When compared against capecitabine alone, the addition of lapatinib has a cost-effectiveness ratio exceeding the threshold normally used by NICE. Compared with T+C, L+C is dominant in the base case and approximately equally likely to be cost-effective in probabilistic sensitivity analyses over a wide range of threshold values.

An equity-effectiveness framework linking health programs and healthy life expectancy.

South Australia's Strategic Plan includes a target to improve the population's healthy life expectancy. A common question among health policy and service planners is: 'How do health programs and services in the community relate to healthy life expectancy?' In response, this paper outlines an effectiveness and equity framework (EEF) for evaluating health interventions in applied settings. Using the example of coronary heart disease (CHD) management in general practice in South Australia, the EEF: (1) applies an internally consistent approach to accounting for population healthy life expectancy at state and smaller geographic levels; (2) estimates average population health gains from health programs, and gains across different socioeconomic subgroups within the community; (3) conducts economic evaluation by equating health gains against health system costs in population subgroups; (4) summarises relevant information about candidate intervention programs within a multi-criteria performance matrix for presentation to decision makers; (5) reassesses outcomes (and processes) following the implementation of a program and iteratively adds to the relevant knowledge and evidence base. The EEF offers a practical approach to selecting and evaluating intervention programs. The challenge is to develop system culture and data capture methods clearly focussed on linking health system activities to population health outcomes.

Cost-Benefit Analysis of Endocrine Therapy in the Adjuvant Setting for Postmenopausal Patients with Hormone Receptor-Positive Breast Cancer, Based on Survival Data and Future Prices for Generic Drugs in the Context of the German Health Care System.

BACKGROUND: Cost-effectiveness analyses have focused on aromatase inhibitors (AIs), but the results are inconsistent and disease-free survival has often been extrapolated to overall survival. The present study calculates the cost-effectiveness of 5 years of letrozole versus tamoxifen versus anastrozole in the context of the German health care system, using survival data from the Breast International Group (BIG) 1-98 study and the Arimidex, Tamoxifen, Alone or in Combination (ATAC) study and generic prices. MATERIALS AND METHODS: A hybrid model was developed that incorporates recurrence rates, overall survival, treatment costs and treatment-associated adverse events and the resulting costs. The basic assumption was that generic anastrozole would lead to a price reduction to 75% of the original price. Further analyses were carried out with 50% and 25% of the original prices for anastrozole and letrozole. RESULTS: The cost-benefit model showed a gain of 0.3124 or 0.0659 quality-adjusted life years (QALYs) for letrozole or anastrozole. Incremental costs of € 29,375.15/QALY for letrozole (100% of original price) were calculated and € 94,648.03/QALY for anastrozole (75% of original price). Marked increases in cost-effectiveness are observed with further decreases in price (anastrozole: 50% price € 54,715.17/QALY, 25% price € 14,779.57/QALY; letrozole 75% price € 20,988.59/QALY, 50% price € 12,602.03/QALY, 25% price € 4,215.46/QALY). CONCLUSION: The present model including the inverse probability of censoring weighted analysis (IPCW) for letrozole and generic prices for both AIs shows that letrozole is cost effective.

The value of value of information: best informing research design and prioritization using current methods.

Value of information (VOI) methods have been proposed as a systematic approach to inform optimal research design and prioritization. Four related questions arise that VOI methods could address. (i) Is further research for a health technology assessment (HTA) potentially worthwhile? (ii) Is the cost of a given research design less than its expected value? (iii) What is the optimal research design for an HTA? (iv) How can research funding be best prioritized across alternative HTAs? Following Occam's razor, we consider the usefulness of VOI methods in informing questions 1-4 relative to their simplicity of use. Expected value of perfect information (EVPI) with current information, while simple to calculate, is shown to provide neither a necessary nor a sufficient condition to address question 1, given that what EVPI needs to exceed varies with the cost of research design, which can vary from very large down to negligible. Hence, for any given HTA, EVPI does not discriminate, as it can be large and further research not worthwhile or small and further research worthwhile. In contrast, each of questions 1-4 are shown to be fully addressed (necessary and sufficient) where VOI methods are applied to maximize expected value of sample information (EVSI) minus expected costs across designs. In comparing complexity in use of VOI methods, applying the central limit theorem (CLT) simplifies analysis to enable easy estimation of EVSI and optimal overall research design, and has been shown to outperform bootstrapping, particularly with small samples. Consequently, VOI methods applying the CLT to inform optimal overall research design satisfy Occam's razor in both improving decision making and reducing complexity. Furthermore, they enable consideration of relevant decision contexts, including option value and opportunity cost of delay, time, imperfect implementation and optimal design across jurisdictions. More complex VOI methods such as bootstrapping of the expected value of partial EVPI may have potential value in refining overall research design. However, Occam's razor must be seriously considered in application of these VOI methods, given their increased complexity and current limitations in informing decision making, with restriction to EVPI rather than EVSI and not allowing for important decision-making contexts. Initial use of CLT methods to focus these more complex partial VOI methods towards where they may be useful in refining optimal overall trial design is suggested. Integrating CLT methods with such partial VOI methods to allow estimation of partial EVSI is suggested in future research to add value to the current VOI toolkit.

Cost-effectiveness analysis of adjuvant therapy for operable breast cancer from a Chinese perspective: doxorubicin plus cyclophosphamide versus docetaxel plus cyclophosphamide.

An oncology trial compared four cycles of doxorubicin/cyclophosphamide (AC) with four cycles of docetaxel/cyclophosphamide (TC) in operable breast cancer patients (71% were diagnosed with hormone receptor positive and 48% with node-negative breast cancer). The objective of this study was to estimate the lifetime cost effectiveness of AC versus TC, from a Chinese healthcare provider perspective, based on a clinical trial. A lifetime cost-effectiveness analysis was performed using a Markov model. Events rates and utilities in the Markov model were derived from published papers. Data on cost of breast cancer care were obtained from the Second Xiangya Hospital of Central South University, Changsha, PR China. One-way sensitivity analysis and probabilistic sensitivity analysis were undertaken. Cost estimates were valued in Chinese yuan (Y), year 2008 values. All costs and outcomes were discounted at 3% per annum. Patients receiving TC gained 14.45 QALYs, 0.41 QALYs more than patients receiving AC. The lifetime costs of patients receiving TC were Y93 511, Y10 116 more than that of AC patients. The incremental cost-effectiveness ratios were Y26 742 per life-year gained ( pound 2719.8 per year) and Y24 305 per QALY gained ( pound2471.9 per QALY). The most sensitive parameter in the model was the cost of primary cancer treatments in the TC arm. At a threshold willingness to pay of Y86 514 per QALY, the probability of TC being cost effective was 90%. Our model suggests that TC may be considered cost effective from a Chinese healthcare provider perspective, according to the threshold defined by the WHO.

Cost-effectiveness of letrozole versus tamoxifen as initial adjuvant therapy in hormone receptor-positive postmenopausal women with early-stage breast cancer.

BACKGROUND: In Breast International Group (BIG) 1-98, a randomized, double-blind trial comparing 5 years of initial adjuvant therapy with letrozole versus tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer, letrozole significantly improved disease-free survival by 19% and reduced risk of breast cancer recurrence by 28% and distant recurrence by 27%. PATIENTS AND METHODS: A Markov model was used to estimate the incremental cost per quality-adjusted life year (QALY) gained with 5 years of initial adjuvant therapy with letrozole versus tamoxifen from a US health care system perspective. Probabilities and costs of breast cancer recurrence and treatment-related adverse events and health-state utilities were based on published results of BIG 1-98 and other published studies. Costs and QALYs were estimated over the lifetime of a cohort of postmenopausal women with hormone receptor-positive early breast cancer, aged 60 years at initiation of therapy. In our base case, we assumed that benefits of letrozole on risk of breast cancer recurrence are maintained for 5 years after therapy discontinuation ("carry-over effect") and examined the effects of this assumption on results in sensitivity analyses. RESULTS: Under base-case assumptions, letrozole yields an additional 0.409 QALYs versus tamoxifen at an additional cost of $9705, yielding a cost per QALY gained for letrozole versus tamoxifen of $23,743 (95% confidence interval, $14,087-$51,129). Assuming no carry-over effects, letrozole yields 0.264 QALYs at a cost of $10,341, for a cost per QALY gained of $39,098 (95% confidence interval, $23,968- $83,501). CONCLUSION: In postmenopausal women with hormone receptor-positive early breast cancer, initial adjuvant treatment with letrozole is cost-effective from the US health care system perspective.

Cost-effectiveness of letrozole in the extended adjuvant treatment of women with early breast cancer.

Adjuvant tamoxifen therapy for 5 years reduces recurrence in hormone receptor positive, post-menopausal women with early breast cancer, but offers no advantage when prolonged to another 5 years, during which the risk of recurrence remains high. Treating patients, who remain disease-free after 5 years of tamoxifen, with letrozole significantly reduces recurrence, regardless of nodal status. This study evaluated the life-time cost-utility of extended adjuvant letrozole therapy in 62-year-old patients from a third-party payer perspective. A Markov model incorporated locoregional, contralateral, and metastatic recurrences. The comparator was placebo. Event rates were based on published trials. Utility values were taken from a clinical trial and published literature. Costs were obtained from published literature, provincial payment schedules, cancer agencies, and drug plans formularies. Resource use reflected Canadian treatment patterns. Robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Extended adjuvant letrozole therapy of a cohort consisting of 50% node-negative and 50% node-positive patients prolonged their lives on average by 0.466 years or 0.267 quality-adjusted life years (QALYs) at an additional cost of Can$8,031 per patient, yielding an incremental cost-utility ratio (ICUR) of $34,058 per QALY. Letrozole was more cost-effective in node-positive than in node-negative patients (Can$26,553 vs Can$46,049 per QALY). Results were robust to variations in age, healthcare costs, and utilities. The degree of confidence that the cost per QALY would be below Can$50,000 reached 100% for node-positive and 77% for node-negative patients. Extended adjuvant letrozole is cost-effective in both node-negative and node-positive patients having ICURs below Can$50,000/QALY.

Modelling the long term cost effectiveness of clopidogrel for the secondary prevention of occlusive vascular events in the UK.

OBJECTIVE: To assess the long term cost effectiveness of clopidogrel monotherapy compared with acetylsalicylic acid (aspirin; ASA) monotherapy in patients at risk of secondary occlusive vascular events (OVEs) in the UK. DESIGN: Cost utility analysis based on clinical data from CAPRIE (a multicentre randomised controlled trial, involving 19185 patients); long-term effects were extrapolated beyond the trial period using a Markov model populated with data from UK observational studies. Health economic evaluation carried out from the perspective of the UK National Health Service. PARTICIPANTS: A representative cohort of 1000 UK patients aged 60 years (approximate mean age of the CAPRIE population), with the qualifying diagnoses of myocardial infarction, ischaemic stroke and peripheral arterial disease, who are at risk of secondary OVEs (non-fatal myocardial infarction, non-fatal stroke or vascular death). INTERVENTIONS: Patients were assumed to receive treatment with either clopidogrel (75 mg/day) for 2 years followed by ASA (325 mg/day, average) for their remaining lifetime, or ASA alone (325 mg/day, average) for life. MAIN OUTCOME MEASURES: Incremental cost per life year gained and incremental cost per quality-adjusted life year (QALY) gained. RESULTS: In the base case, the incremental cost effectiveness of clopidogrel versus ASA in this population is estimated at 18888 pounds per life year gained and 21 489 pounds per QALY gained. Multiple deterministic and probabilistic sensitivity analyses suggest the model is robust to variations in a wide range of input parameters. CONCLUSION: Two years of treatment with clopidogrel can be considered a cost effective intervention in patients at risk of secondary OVEs in the UK.

A stochastic economic evaluation of letrozole versus tamoxifen as a first-line hormonal therapy: for advanced breast cancer in postmenopausal patients.

BACKGROUND: Letrozole is a third-generation aromatase inhibitor that is a feasible alternative to tamoxifen as a first-line hormonal therapy for patients with advanced breast cancer. OBJECTIVE: This paper presents the results of an economic evaluation comparing letrozole and tamoxifen as first-line hormonal therapies in postmenopausal women diagnosed with advanced breast cancer. PERSPECTIVE: UK National Health Service. DESIGN: A decision model (Markov process) was built describing possible patient pathways from the point of diagnosis to death. The model was populated using patient-specific clinical trial data, data from the existing literature, and expert opinion. Stochastic analyses of the model were undertaken, whereby the majority of the input parameters were described as probability distributions to represent the uncertainty about their true value. Costs were presented in year 2000 values. RESULTS: The baseline results showed that letrozole is a cost-effective alternative to tamoxifen with a mean incremental cost per life-year gained of pound 2342, whilst the incremental cost increases to just over pound 10,000 at the 95th percentile of the cost-effectiveness range (2000 values). CONCLUSIONS: The results of the economic analysis indicate that letrozole is a cost-effective alternative first-line therapy compared with tamoxifen for postmenopausal women with advanced breast cancer, achieving additional life-years with a modest increase in costs.