Synthesized economic evidence on the cost-effectiveness of screening familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is a prevalent genetic disorder with global implications for severe cardiovascular diseases. Motivated by the growing recognition of the need for early diagnosis and treatment of FH to mitigate its severe consequences, alongside the gaps in understanding the economic implications and equity impacts of FH screening, this study aims to synthesize the economic evidence on the cost-effectiveness of FH screening and to analyze the impact of FH screening on health inequality. METHODS: We conducted a systematic review on the economic evaluations of FH screening and extracted information from the included studies using a pre-determined form for evidence synthesis. We synthesized the cost-effectiveness components involving the calculation of synthesized incremental cost-effectiveness ratios (ICERs) and net health benefit (NHB) of different FH screening strategies. Additionally, we applied an aggregate distributional cost-effectiveness analysis (DCEA) to assess the impact of FH screening on health inequality. RESULTS: Among the 19 studies included, over half utilized Markov models, and 84% concluded that FH screening was potentially cost-effective. Based on the synthesized evidence, cascade screening was likely to be cost-effective, with an ICER of $49,630 per quality-adjusted life year (QALY). The ICER for universal screening was $20,860 per QALY as per evidence synthesis. The aggregate DCEA for six eligible studies presented that the incremental equally distributed equivalent health (EDEH) exceeded the NHB. The difference between EDEH and NHB across the six studies were 325, 137, 556, 36, 50, and 31 QALYs, respectively, with an average positive difference of 189 QALYs. CONCLUSIONS: Our research offered valuable insights into the economic evaluations of FH screening strategies, highlighting significant heterogeneity in methods and outcomes across different contexts. Most studies indicated that FH screening is cost-effective and contributes to improving overall population health while potentially reducing health inequality. These findings offer implications that policies should promote the implementation of FH screening programs, particularly among younger population. Optimizing screening strategies based on economic evidence can help identify the most effective measures for improving health outcomes and maximizing cost-effectiveness.

Histopathologically Validated Diagnostic Accuracy of PSMA-PET/CT in the Primary and Secondary Staging of Prostate Cancer and the Impact of PSMA-PET/CT on Clinical Management: A Systematic Review and Meta-analysis.

Prostate-specific membrane antigen (PSMA) is a highly expressed protein in prostate cancer (PCa) and has become an increasingly popular target for molecular imaging in recent years. PSMA based positron-emission-tomography/computed tomography (PET/CT) is a well characterised hybrid imaging modality that combines the high sensitivity of PET with the high spatial resolution of CT imaging. The combination of these two imaging modalities provides an accurate tool for detecting and managing PCa. Several diagnostic accuracy and clinical management studies investigating the role of PSMA PET/CT in PCa have been published recently. This study aimed to perform an updated systematic review and meta-analysis to evaluate the diagnostic performance of PSMA PET/CT in localised, lymph node metastatic (LNM) and recurrent PCa patients and assess its impact on the clinical management of primary and recurrent PCa. Using Medline, Embase, PubMed and Cochrane Library databases, studies reporting the diagnostic accuracy and clinical management of PSMA PET/CT were analysed based on the PRISMA guidelines. Statistical analyses were conducted using random-effects models, and meta-regression explored observed heterogeneity. Results indicate that the sensitivity and specificity of PSMA PET/CT for localised PCa were 71.0% (95% confidence interval (CI): 58.0, 81.0) and 92.0% (95% CI: 86.0, 96.0), respectively (N = 10; n = 404 patients). Sensitivity and specificity in LNM were 57.0% (95% CI: 49.0, 64.0) and 96.0% (95% CI: 95.0, 97.0) (N = 36; n = 3,659 patients). For patients with biochemical recurrence (BCR), sensitivity was 84.0% (95% CI: 74.0, 90.0), and specificity was 97.0% (95% CI: 88.0, 99.0) (N = 9; n = 818 patients). The pooled proportion of management changes in primary (N = 16; n = 1,099 patients) and recurrent (N = 40; n = 5,398 patients) PCa was 28.0% (95% CI: 23.0, 34.0) and 54.0% (95% CI: 50.0, 58.0), respectively. In conclusion, PSMA PET/CT shows moderate sensitivity and high specificity in localised and LNM disease, while the accuracy in BCR patients was high. PSMA PET/CT also had a large impact on the clinical management of PCa patients. This is the most extensive and first systematic review to include three subgroups of PCa with histologically verified diagnostic accuracy and clinical management change reported separately in primary and recurrent disease settings.

Microcosting Study of Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Prostate Cancer.

OBJECTIVES: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has emerged as a promising imaging tool in prostate cancer diagnosis. PSMA PET/CT radiotracers are produced in-house (gallium-68, eg, 68Ga-PSMA-11) or provided by commercial entities (fluorine-18, eg, 18F-DCFPyL). Nevertheless, the cost per procedure is not well established given that current estimates have several limitations. This study aimed to establish the cost of PSMA PET/CT in Australia. METHODS: Hospitals and diagnostic facilities currently conducting PSMA PET/CT in Australia in metropolitan and regional areas completed a survey of PSMA PET/CT throughput, radiotracers involved, and the cost of assets, departmental staffing, consumables, and occupancy. Total costs were estimated using a top-down microcosting approach, involving identifying all relevant cost components and valuing each component for the average patient, and a gross costing approach, involving apportioning cost components at an aggregated level. RESULTS: Data were collected from 8 facilities. The most common radiotracer used was 18F-DCFPyL (7 facilities, 87%), followed by 68Ga-PSMA-11 (4 facilities, 50%). The average cost of PSMA PET/CT was A$1554.77 and A$1306.00 based on the microcosting and gross costing approaches, respectively. CONCLUSIONS: This study provides a detailed and accurate estimation of the cost of PSMA PET/CT in Australia. These costs can be used as a benchmark to identify potential efficiencies and help policy makers set the appropriate reimbursement rate for this procedure. The use of data from facilities using different radiotracers in metropolitan and regional areas and with different throughput increases the generalizability of the results, especially in countries with similar health systems.

Cost-Effectiveness Analysis of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) for the Primary Staging of Prostate Cancer in Australia.

BACKGROUND AND OBJECTIVES: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) combined with computed tomography (CT) is a new imaging modality to detect the extra-prostatic spread of prostate cancer. PSMA PET/CT has a higher sensitivity and specificity than conventional imaging (CT ± whole body bone scan [WBBS]). This study conducted a cost-utility analysis of PSMA PET/CT compared with conventional imaging for patients with newly diagnosed, intermediate-risk or high-risk primary prostate cancer. PERSPECTIVE: Australian healthcare perspective. SETTING: Tertiary. METHODS: A decision-analytic Markov model combined data from a variety of sources. The time horizon was 35 years. The sensitivity and specificity of PSMA PET/CT and CT alone were based on meta-analyses and the test accuracy of CT+WBBS was based on a single randomised controlled trial. Health outcomes included cases detected, life-years, and quality-adjusted life-years. Costs related to other diagnostic tests, initial treatment, adverse events, and post-disease progression were included. All costs were reported in 2021 Australian Dollars (A$). RESULTS: The deterministic incremental cost-effectiveness ratio of PSMA PET/CT was estimated to be A $21,147/quality-adjusted life-year gained versus CT+WBBS, and A$36,231/quality-adjusted life-year gained versus CT alone. The results were most sensitive to the time horizon, and the initial treatments received by patients diagnosed with metastatic cancer. The probability of PSMA PET/CT being cost effective was estimated to be 91% versus CT+WBBS and 89% versus CT alone, using a threshold of AU$50,000/quality-adjusted life-year gained. CONCLUSIONS: PSMA PET/CT is likely to be more costly than CT+WBBS or CT alone in Australia; however, it is still likely to be considered cost effective compared with conventional imaging.

Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals.

BACKGROUND: To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3-5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states. METHODS: We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals. RESULTS: Tumour testing approaches differed between hospitals, with 0-19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients). CONCLUSIONS: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.

The cost-effectiveness of unilateral cochlear implants in UK adults.

OBJECTIVE: The National Institute for Health and Care Excellence (NICE) updated its eligibility criteria for unilateral cochlear implants (UCIs) in 2019. NICE claimed this would not impact the cost-effectiveness results used within its 2009 technology appraisal guidance. This claim is uncertain given changed clinical practice and increased healthcare unit costs. Our objective was to estimate the cost-effectiveness estimates of UCIs in UK adults with severe to profound hearing loss within the contemporary NHS environment. METHODS: A cost-utility analysis employing a Markov model was undertaken to compare UCIs with hearing aids or no hearing aids for people with severe to profound hearing loss. A clinical pathway was developed to estimate resource use. Health-related quality of life, potential adverse events, device upgrades and device failure were captured. Unit costs were derived mostly from the NHS data. Probabilistic sensitivity analysis further assessed the effect of uncertain model inputs. RESULTS: A UCI is likely to be deemed cost-effective when compared to a hearing aid (£11,946/QALY) or no hearing aid (£10,499/QALY). A UCI has an 93.0% and 98.7% likelihood of being cost-effective within the UK adult population when compared to a hearing aid or no hearing aid, respectively. ICERs were mostly sensitive to the proportion of people eligible for cochlear implant, discount rate, surgery and device costs and processor upgrade cost. CONCLUSION: UCIs remain cost-effective despite changes to clinical practice and increased healthcare unit costs. Updating the NICE criteria to provide better access UCIs is projected to increase annual implants in adults and children by 70% and expenditure by £28.6 million within three years. This increased access to UCIs will further improve quality of life of recipients and overall social welfare.

Understanding implementation success: protocol for an in-depth, mixed-methods process evaluation of a cluster randomised controlled trial testing methods to improve detection of Lynch syndrome in Australian hospitals.

INTRODUCTION: In multisite intervention trials, implementation success often varies widely across settings. Process evaluations are crucial to interpreting trial outcomes and understanding contextual factors and causal chains necessary for successful implementation. Lynch syndrome is a hereditary cancer predisposition conferring an increased risk of colorectal, endometrial and other cancer types. Despite systematic screening protocols to identify Lynch syndrome, the condition remains largely underdiagnosed. The Hide and Seek Project ('HaSP') is a cluster randomised controlled trial determining the effectiveness of two approaches to improving Lynch syndrome detection at eight Australian hospital networks. To enhance widespread implementation of optimal Lynch syndrome identification, there is a need to understand not only what works, but also why, in what contexts, and at what costs. Here we describe an in-depth investigation of factors influencing successful implementation of procedures evaluated in the HaSP trial. METHODS AND ANALYSIS: A mixed-methods, theory-driven process evaluation will be undertaken in parallel to the HaSP trial. Data will include: interviews of Implementation Leads and Lynch syndrome stakeholders, pre-post implementation questionnaires, audio analysis of meetings and focus groups, observation of multidisciplinary team meetings, fidelity checklists and project log analysis. Results will be triangulated and coded, drawing on the Theoretical Domains Framework, Consolidated Framework for Implementation Research and Proctor's implementation outcomes. ETHICS AND DISSEMINATION: Use of a theory-based process evaluation will enhance interpretation and generalisability of HaSP trial findings, and contribute to the implementation research field by furthering understanding of the conditions necessary for implementation success. Ethical approval has been granted and results will be disseminated via publications in peer-reviewed journals and conference presentations. At trial completion, key findings will be fed back to sites to enable refinement of intervention strategies, both in the context of Lynch syndrome and for the possible generalisability of intervention components in other genetic and broader clinical specialties. HASP TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (Identifier: ACTRN12618001072202). Registered 27 June 2018. http://www.ANZCTR.org.au/ACTRN12618001072202.aspx.

Pathways to a cancer-free future: a protocol for modelled evaluations to minimise the future burden of colorectal cancer in Australia.

INTRODUCTION: With almost 50% of cases preventable and the Australian National Bowel Cancer Screening Program in place, colorectal cancer (CRC) is a prime candidate for investment to reduce the cancer burden. The challenge is determining effective ways to reduce morbidity and mortality and their implementation through policy and practice. Pathways-Bowel is a multistage programme that aims to identify best-value investment in CRC control by integrating expert and end-user engagement; relevant evidence; modelled interventions to guide future investment; and policy-driven implementation of interventions using evidence-based methods. METHODS AND ANALYSIS: Pathways-Bowel is an iterative work programme incorporating a calibrated and validated CRC natural history model for Australia (Policy1-Bowel) and assessing the health and cost outcomes and resource use of targeted interventions. Experts help identify and prioritise modelled evaluations of changing trends and interventions and critically assess results to advise on their real-world applicability. Where appropriate the results are used to support public policy change and make the case for optimal investment in specific CRC control interventions. Fourteen high-priority evaluations have been modelled or planned, including evaluations of CRC outcomes from the changing prevalence of modifiable exposures, including smoking and body fatness; potential benefits of daily aspirin intake as chemoprevention; increasing CRC incidence in people aged <50 years; increasing screening participation in the general and Aboriginal and Torres Strait Islander populations; alternative screening technologies and modalities; and changes to follow-up surveillance protocols. Pathways-Bowel is a unique, comprehensive approach to evaluating CRC control; no prior body of work has assessed the relative benefits of a variety of interventions across CRC development and progression to produce a list of best-value investments. ETHICS AND DISSEMINATION: Ethics approval was not required as human participants were not involved. Findings are reported in a series of papers in peer-reviewed journals and presented at fora to engage the community and policymakers.

Comparing theory and non-theory based implementation approaches to improving referral practices in cancer genetics: a cluster randomised trial protocol.

BACKGROUND: Lynch syndrome (LS) is an inherited, cancer predisposition syndrome associated with an increased risk of colorectal, endometrial and other cancer types. Identifying individuals with LS allows access to cancer risk management strategies proven to reduce cancer incidence and improve survival. However, LS is underdiagnosed and genetic referral rates are poor. Improving LS referral is complex, and requires multisystem behaviour change. Although barriers have been identified, evidence-based strategies to facilitate behaviour change are lacking. The aim of this study is to compare the effectiveness of a theory-based implementation approach against a non-theory based approach for improving detection of LS amongst Australian patients with colorectal cancer (CRC). METHODS: A two-arm parallel cluster randomised trial design will be used to compare two identical, structured implementation approaches, distinguished only by the use of theory to identify barriers and design targeted intervention strategies, to improve LS referral practices in eight large Australian hospital networks. Each hospital network will be randomly allocated to a trial arm, with stratification by state. A trained healthcare professional will lead the following phases at each site: (1) undertake baseline clinical practice audits, (2) form multidisciplinary Implementation Teams, (3) identify target behaviours for practice change, (4) identify barriers to change, (5) generate intervention strategies, (6) support staff to implement interventions and (7) evaluate the effectiveness of the intervention using post-implementation clinical data. The theoretical and non-theoretical components of each trial arm will be distinguished in phases 4-5. Study outcomes include a LS referral process map for each hospital network, with evaluation of the proportion of patients with risk-appropriate completion of the LS referral pathway within 2 months of CRC resection pre and post implementation. DISCUSSION: This trial will determine the more effective approach for improving the detection of LS amongst patients with CRC, whilst also advancing understanding of the impact of theory-based implementation approaches in complex health systems and the feasibility of training healthcare professionals to use them. Insights gained will guide the development of future interventions to improve LS identification on a larger scale and across different contexts, as well as efforts to address the gap between evidence and practice in the rapidly evolving field of genomic research. TRIAL REGISTRATION: ANZCTR, ACTRN12618001072202 . Registered on 27 June 2018.

Is Reclassification of the Oral Contraceptive Pill from Prescription to Pharmacist-Only Cost Effective? Application of an Economic Evaluation Approach to Regulatory Decisions.

BACKGROUND AND OBJECTIVE: Unplanned pregnancies can lead to poorer maternal and child health outcomes. The Australian Therapeutic Goods Administration committee rejected reclassifying a range of oral contraceptive pills (OCPs) from prescription to pharmacist-only medicines in 2015, mainly based on safety concerns. Improving access to OCPs may encourage some women to use contraceptives or switch from other contraceptive methods. However, some adverse events may increase and some women may stop using condoms, increasing their risk of sexually transmitted infections. This study aimed to estimate the cost effectiveness of reclassifying OCPs from prescription to pharmacist-only. PERSPECTIVE: Healthcare system. SETTING: Australian primary care. METHODS: A Markov model was used to synthesise data from a variety of sources. The model included all Australian women aged 15-49 years (N = 5,644,701). The time horizon was 35 years. Contraceptive use before reclassification was estimated using data from the Household, Income and Labour Dynamics in Australia (HILDA) survey, while survey data informed use after reclassification. Health outcomes included pregnancies, pregnancy outcomes (live birth, miscarriage, stillbirth, ectopic pregnancy and abortion), sexually transmitted infections, adverse events (venous thromboembolism, depression, myocardial infarction and stroke), ovarian cancer cases and quality-adjusted life-years. Costs included those related to general practitioner and specialist consultations, contraceptives and other medicines, pharmacist time, hospitalisations and adverse events. All costs were reported in 2016 Australian Dollars. A 5% discount rate was applied to health outcomes and costs. RESULTS: Reclassifying OCPs resulted in 85.70 million quality-adjusted life-years experienced and costs of $46,910.14 million over 35 years, vs. 85.68 million quality-adjusted life-years experienced and costs of $50,274.95 million with OCPs remaining prescription-only. Thus, reclassifying OCPs was more effective and cost saving. However, a sensitivity analysis found that more research on the probability of pregnancy in women not using contraception and not trying to conceive is needed. CONCLUSION: Reclassifying OCPs is likely to be considered cost effective by Australian decision makers.

Economic Evaluations of Childhood Hearing Loss Screening Programmes: A Systematic Review and Critique.

BACKGROUND: Permanent childhood hearing loss is one of the most common birth conditions associated with speech and language delay. A hearing screening can result in early detection and intervention for hearing loss. OBJECTIVES: To update and expand previous systematic reviews of economic evaluations of childhood hearing screening strategies, and explore the methodological differences. DATA SOURCES: MEDLINE, Embase, the Cochrane database, National Health Services Economic Evaluation Database (NHS EED), the Health Technology Assessment (HTA) database, and Canadian Agency for Drugs and Technologies in Health's (CADTH) Grey matters. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Economic evaluations reporting costs and outcomes for both the intervention and comparator arms related to childhood hearing screening strategies. RESULTS: Thirty evaluations (from 29 articles) were included for review. Several methodological issues were identified, including: few evaluations reported outcomes in terms of quality-adjusted life years (QALYs); none estimated utilities directly from surveying children; none included disutilities and costs associated with adverse events; few included costs and outcomes that differed by severity; few included long-term estimates; none considered acquired hearing loss; some did not present incremental results; and few conducted comprehensive univariate or probabilistic sensitivity analysis. Evaluations published post-2011 were more likely to report QALYs and disability-adjusted life years (DALYs) as outcome measures, include long-term treatment and productivity costs, and present incremental results. LIMITATIONS: We were unable to access the economic models and, although we employed an extensive search strategy, potentially not all relevant economic evaluations were identified. CONCLUSIONS AND IMPLICATIONS: Most economic evaluations concluded that childhood hearing screening is value for money. However, there were significant methodological limitations with the evaluations.

The Real-World Cost-Effectiveness of Coronary Artery Bypass Surgery Versus Stenting in High-Risk Patients: Propensity Score-Matched Analysis of a Single-Centre Experience.

BACKGROUND: There are limited economic evaluations comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for multi-vessel coronary artery disease (MVCAD) in contemporary, routine clinical practice. OBJECTIVE: The aim was to perform a cost-effectiveness analysis comparing CABG and PCI in patients with MVCAD, from the perspective of the Australian public hospital payer, using observational data sources. METHODS: Clinical data from the Melbourne Interventional Group (MIG) and the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registries were analysed for 1022 CABG (treatment) and 978 PCI (comparator) procedures performed between June 2009 and December 2013. Clinical records were linked to same-hospital admissions and national death index (NDI) data. The incremental cost-effectiveness ratios (ICERs) per major adverse cardiac and cerebrovascular event (MACCE) avoided were evaluated. The propensity score bin bootstrap (PSBB) approach was used to validate base-case results. RESULTS: At mean follow-up of 2.7 years, CABG compared with PCI was associated with increased costs and greater all-cause mortality, but a significantly lower rate of MACCE. An ICER of $55,255 (Australian dollars)/MACCE avoided was observed for the overall cohort. The ICER varied across comparisons against bare metal stents (ICER $25,815/MACCE avoided), all drug-eluting stents (DES) ($56,861), second-generation DES ($42,925), and third-generation of DES ($88,535). Moderate-to-low ICERs were apparent for high-risk subgroups, including those with chronic kidney disease ($62,299), diabetes ($42,819), history of myocardial infarction ($30,431), left main coronary artery disease ($38,864), and heart failure ($36,966). CONCLUSIONS: At early follow-up, high-risk subgroups had lower ICERs than the overall cohort when CABG was compared with PCI. A personalised, multidisciplinary approach to treatment of patients may enhance cost containment, as well as improving clinical outcomes following revascularisation strategies.

Cost-effectiveness of the BRECONDA decision aid for women with breast cancer: Results from a randomized controlled trial.

OBJECTIVE: To report on the cost-effectiveness of BRECONDA (Breast RECONstruction Decision Aid), a web-based decision aid to facilitate decisions regarding breast reconstruction surgery, with usual care for women with breast cancer. METHODS: The economic evaluation was conducted alongside a randomized controlled trial. Women diagnosed with breast cancer or ductal carcinoma in situ and eligible for breast reconstruction following mastectomy were randomized to access BRECONDA for 6 months + usual care (n = 106) or usual care (n = 116) and were assessed at baseline preintervention, and then 1-month and 6-months post-randomization. Decisional conflict, satisfaction with information, decisional regret, and utilities were assessed by using maximum-likelihood linear mixed effects models. Costs included the fixed costs of BRECONDA, health care provider time, and health care resource use. Nonparametric bootstrapping was used to estimate incremental cost-effectiveness ratios. RESULTS: BRECONDA resulted in significantly less decisional conflict and greater satisfaction with information over time. Quality-adjusted life years did not differ between participants who received the decision aid compared with usual care. The cost of BRECONDA was estimated to be small (AUD$10) relative to other health care interventions and resulted in decreased health care costs overall (AUD$764). Based on the point estimates, the decision aid was more effective and less costly (dominant) for all measures of effectiveness. It was estimated that the decision aid has an 87% probability of being cost-effective at $60 000 per quality-adjusted life year gained. CONCLUSIONS: The BRECONDA web-based intervention designed to facilitate decisions regarding breast reconstruction surgery is likely to be cost-effective compared with usual care for women with breast cancer.

Financial cost of lymphedema borne by women with breast cancer.

OBJECTIVE: Our study examines the financial cost of lymphedema following a diagnosis of breast cancer and addresses a significant knowledge gap regarding the additional impact of lymphedema on breast cancer survivors. METHODS: An online national survey was conducted with 361 women who had either breast cancer without lymphedema (BC) (group 1, n = 209) or breast cancer with lymphedema (BC+LE) (group 2, n = 152). Participant recruitment was supported by the Breast Cancer Network Australia and the Australasian Lymphology Association. RESULTS: Both breast cancer and lymphedema result in significant out-of-pocket financial costs borne by women. Of patients with BC+LE, 80% indicated that their breast cancer diagnosis had affected them financially compared with 67% in the BC group (P < .020). For patients with lymphedema, over half (56%) indicated that this specific additional diagnosis to their breast cancer affected them financially and that costs increased with lymphedema severity. The cost of compression garments formed a large proportion of these costs (40.1%). The average number of attendances to a therapist each year was 5.8 (range, 0-45). Twenty-five patients (16.4%) had an episode of cellulitis in the past year. The incidence of cellulitis was 7.7% in 91 patients with subclinical or mild lymphedema compared with 29.5% of 61 patients with more extensive lymphedema (P < .001). The average out-of-pocket financial cost of lymphedema care borne by women was A$977 per annum, ranging from A$207 for subclinical lymphedema to over A$1400 for moderate or severe lymphedema. CONCLUSIONS: This study identifies an additional detrimental effect of lymphedema on women in terms of financial costs.

Long-term health care costs for patients with prostate cancer: a population-wide longitudinal study in New South Wales, Australia.

AIM: Prostate cancer (PCa) is the most commonly diagnosed cancer in Australian males. There are limited data on the long-term health system costs associated with PCa. The aim of this study is to estimate long-term health care costs of PCa. METHODS: We estimated the health system costs for a cohort of 1873 males diagnosed with PCa between 2000 and 2002, using linked medical, pharmaceutical and hospital data. Treatment was defined by an initial phase, measuring health care costs up to 6 months following diagnosis and a continuing phase (including metastatic treatment), measuring treatments to 9.5 years. Nonparametric models were used to calculate average health care costs by PCa risk groups at diagnosis (low to metastatic) and treatment pathways. RESULTS: Health system costs increased with increasing PCa risk category, from $16 923 (low risk) to $39 101 (metastatic risk group). For men with initial localized risk, costs were $8 454 for the active surveillance treatment pathway, $9621 for external beam radiation therapy/brachytherapy, $19 210 for androgen deprivation therapy, $20 636 for radical prostatectomy, $21 161 for radical prostatectomy + external beam radiation therapy/brachytherapy, $21 388 for any of the treatments previously listed + androgen deprivation therapy, with an additional cost of $55 370 if metastatic treatment was undertaken. CONCLUSIONS: Treatment costs are highest during two phases over the natural cycle of the disease, the initial diagnosis phase and the metastatic treatment phase. Both the initial phase costs and low-risk category costs are driven largely by the rates of radical prostatectomy. Our study provides comprehensive long-term estimates of PCa costs.

Real-World Evidence: A Comparison of the Australian Herceptin Program and Clinical Trials of Trastuzumab for HER2-Positive Metastatic Breast Cancer.

INTRODUCTION: Estimating the real-world cost-effectiveness of a new drug relies on understanding the differences between clinical trial data (pre-reimbursement) and clinical practice (post-reimbursement). This is important for decision makers when reviewing reimbursement decisions, prices, and considering other drugs for the same condition. Differences can arise from differences in patient characteristics, but also from the availability of new evidence and evolving treatment practices. This paper examines these issues using a case study. METHODS: In 2001, the Australian Government funded trastuzumab for the treatment of HER2+ metastatic breast cancer through the Herceptin Program. The administrative arrangements of the Program resulted in rich observational data that captured information about patients treated with trastuzumab between 2001 and 2010 (n = 3830). The dataset included patient characteristics, dispensed medicines, medical service use and date of death. RESULTS: Compared to participants in the clinical trials, patients were older, received more prior chemotherapies and a broader range of co-administered chemotherapies. Treatment practices differed from the clinical trials, but also changed over time. For example, in situ hybridization testing, rather than immunohistochemistry testing, and a three weekly administration schedule, rather than one weekly, were increasingly used. Compared to the clinical trials, patients administered trastuzumab with a concomitant chemotherapy generally experienced longer overall survival (151.3 weeks, 95 % CI: 142.6, 163.4), while those who received trastuzumab as a monotherapy experienced shorter overall survival (94.4 weeks, 95%CI: 86.4, 102.9). These findings may be due to a differing relative treatment effect in clinical practice, but may also be due to a range of other factors. CONCLUSION: This analysis demonstrates the challenges for decision makers that arise because new evidence and evolving treatment practices create a gap between clinical trial data and real-world clinical practice and outcomes.

Resource use, costs and quality of end-of-life care: observations in a cohort of elderly Australian cancer decedents.

BACKGROUND: The last year of life is one of the most resource-intensive periods for people with cancer. Very little population-based research has been conducted on end-of-life cancer care in the Australian health care setting. The objective of this program is to undertake a series of observational studies examining resource use, costs and quality of end-of-life care in a cohort of elderly cancer decedents using linked, routinely collected data. METHODS/DESIGN: This study forms part of an ongoing cancer health services research program. The cohorts for the end-of-life research program comprise Australian Government Department of Veterans' Affairs decedents with full health care entitlements, residing in NSW for the last 18 months of life and dying between 2005 and 2009. We used cancer and death registry data to identify our decedent cohorts and their causes of death. The study population includes 9,862 decedents with a cancer history and 15,483 decedents without a cancer history. The median age at death is 86 and 87 years in the cancer and non-cancer cohorts, respectively. We will examine resource use and associated costs in the last 6 months of life using linked claims data to report on health service use, hospitalizations, emergency department visits and medicines use. We will use best practice methods to examine the nature and extent of resource use, costs and quality of care based on previously published indicators. We will also examine factors associated with these outcomes. DISCUSSION: This will be the first Australian research program and among the first internationally to combine routinely collected data from primary care and hospital-based care to examine comprehensively end-of-life care in the elderly. The research program has high translational value, as there is limited evidence about the nature and quality of care in the Australian end-of-life setting.

Economic evaluations of trastuzumab in HER2-positive metastatic breast cancer: a systematic review and critique.

BACKGROUND: Published economic evaluations of trastuzumab for the treatment of HER2-positive metastatic breast cancer have arrived at different conclusions regarding the cost-effectiveness of trastuzumab, despite comparative efficacy being demonstrated by a small set of randomised controlled trials (RCTs). OBJECTIVES: This article aims to provide insight into the quality of the evaluations and explore the possible drivers of the conflicting conclusions. METHODS: A systematic literature review was conducted to identify all published economic evaluations that compared the incremental costs and outcomes of trastuzumab versus a comparator. RESULTS: Fifteen economic evaluations were identified. In the evaluations that estimated efficacy using an RCT, the key drivers of the conclusions regarding cost-effectiveness were: the approach used to estimate overall survival in the control group given crossover to trastuzumab following progression in the trials; the inclusion of treatment beyond progression; inclusion of wastage due to unused vial portions, adverse events, and the cost of HER2 testing. Four evaluations used non-randomised approaches to estimate efficacy, thus introducing the potential for confounding. As a result these evaluations reported relatively optimistic estimates of comparative effectiveness. Finally the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective. CONCLUSION: There were numerous drivers of the different conclusions regarding the cost-effectiveness of trastuzumab, many of which are due to judgements made by the authors when translating data from RCTs. Many of the potential drivers were not identified by the published systematic reviews of economic evaluations and perhaps more remain unidentified because of inconsistent and limited reporting.

The cost-effectiveness of mandatory folic acid fortification in Australia.

The Australian government recently introduced mandatory folic acid fortification of bread to reduce the incidence of neural tube defects (NTDs). The economic evaluation of this policy contained a number of limitations. This study aimed to address the limitations and to reconsider the findings. Cost-effectiveness analysis was used to assess the cost and benefits of mandatory versus voluntary folic acid fortification. Outcomes measures were quality-adjusted life-years (QALYs), life-years gained (LYG), avoided NTD cases, and additional severe neuropathy cases. Costs considered included industry costs and regulatory costs to the government. It was estimated that mandatory fortification would prevent 31 NTDs, whereas an additional 14 cases of severe neuropathy would be incurred. Overall, 539 LYG and 503 QALYs would be gained per year of mandatory compared with voluntary fortification. Mandatory fortification was cost-effective at A$10,723 per LYG and at A$11,485 per QALY. Probabilistic sensitivity analysis showed that at A$60,000 and A$151,000 per QALY, the probability that mandatory fortification was the most cost-effective strategy was 79% and 85%, respectively. Threshold analysis of loss of consumer choice indicated that with a compensation value above A$1.21 [assuming a willingness to pay (WTP) threshold of A$60,000 per QALY] or A$3.19 (assuming a WTP threshold of A$151,000 per statistical life-year) per capita per year mandatory fortification would not be cost-effective. Mandatory fortification was found to be cost-effective; however, inclusion of the loss of consumer choice can change this result. Even with mandatory fortification, mean folate intake will remain below the recommended NTD preventive level.

Cost-effectiveness of lumbar artificial intervertebral disc replacement: driven by the choice of comparator.

BACKGROUND: Lower back pain is a common and costly condition in Australia. This paper aims to conduct an economic evaluation of lumbar artificial intervertebral disc replacement (AIDR) compared with lumbar fusion for the treatment of patients suffering from significant axial back pain and/or radicular (nerve root) pain, secondary to disc degeneration or prolapse, who have failed conservative treatment. METHODS: A cost-effectiveness approach was used to compare costs and benefits of AIDR to five fusion approaches. Resource use was based on Medicare Benefits Schedule claims data and expert opinion. Effectiveness and re-operation rates were based on published randomized controlled trials. The key clinical outcomes considered were narcotic medication discontinuation, achievement of overall clinical success, achievement of Oswestry Disability Index success and quality-adjusted life-years gained. RESULTS: AIDR was estimated to be cost-saving compared with fusion overall ($1600/patient); however, anterior lumbar interbody fusion and posterolateral fusion were less costly by $2155 and $807, respectively. The incremental cost-effectiveness depends on the outcome considered and the comparator. CONCLUSIONS: AIDR is potentially a cost-saving treatment for lumbar disc degeneration, although longer-term follow-up data are required to substantiate this claim. The incremental cost-effectiveness depends on the outcome considered and the comparator, and further research is required before any firm conclusions can be drawn.