Developing a Modeling Framework for Quantifying the Health and Cost Implications of Antibiotic Resistance for Surgical Procedures.

Background. Antimicrobial resistance (AMR) is a global public health threat. The wider implications of AMR, such as the impact of antibiotic resistance (ABR) on surgical procedures, are yet to be quantified. The objective of this study was to produce a conceptual modeling framework to provide a basis for estimating the current and potential future consequences of ABR for surgical procedures in England. Design. A framework was developed using literature-based evidence and structured expert elicitation. This was applied to populations undergoing emergency repair of the neck of the femur and elective colorectal resection surgery. Results. The framework captures the implications of increasing ABR by allowing for higher rates of surgical site infection (SSI) as the effectiveness of antibiotic prophylaxis wanes and worsened outcomes following SSIs to reflect reduced antibiotic treatment effectiveness. The expert elicitation highlights the uncertainty in quantifying the impact of ABR, reflected in the results. A hypothetical SSI rate increase of 14% in a person undergoing emergency repair of the femur could increase costs by 39% (-2% to 108% credible interval [CI]) and decrease quality-adjusted life-years by 11% (0.4% to 62% CI) over 15 y. Conclusions. The modeling framework is a starting point for addressing the implication of ABR on the outcomes and costs of surgeries. Due to clinical uncertainty highlighted in the expert elicitation process, the numerical outputs of the case studies should not be focused on but rather the framework itself, illustration of the evidence gaps, the benefit of expert elicitation in quantifying parameters with limited data, and the potential magnitude of the impact of ABR on surgical procedures. Implications. The framework can be used to support research surrounding the health and cost burden of ABR in England. Highlights: The modeling framework is a starting point for assessing the health and cost impacts of antibiotic resistance on surgeries in England.Formulating a framework and synthesizing evidence to parameterize data gaps provides targets for future research.Once data gaps are addressed, this modeling framework can be used to feed into overall estimates of the health and cost burden of antibiotic resistance and evaluate control policies.

DRUG EVALUATION AND DECISION MAKING IN CATALONIA: DEVELOPMENT AND VALIDATION OF A METHODOLOGICAL FRAMEWORK BASED ON MULTI-CRITERIA DECISION ANALYSIS (MCDA) FOR ORPHAN DRUGS.

OBJECTIVES: The aim of this study was to adapt and assess the value of a Multi-Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of Orphan drugs in Catalonia (Catalan Health Service). METHODS: The standard evaluation and decision-making procedures of CatSalut were compared with the EVIDEM methodology and contents. The EVIDEM framework was adapted to the Catalan context, focusing on the evaluation of Orphan drugs (PASFTAC program), during a Workshop with sixteen PASFTAC members. The criteria weighting was done using two different techniques (nonhierarchical and hierarchical). Reliability was assessed by re-test. RESULTS: The EVIDEM framework and methodology was found useful and feasible for Orphan drugs evaluation and decision making in Catalonia. All the criteria considered for the development of the CatSalut Technical Reports and decision making were considered in the framework. Nevertheless, the framework could improve the reporting of some of these criteria (i.e., "unmet needs" or "nonmedical costs"). Some Contextual criteria were removed (i.e., "Mandate and scope of healthcare system", "Environmental impact") or adapted ("population priorities and access") for CatSalut purposes. Independently of the weighting technique considered, the most important evaluation criteria identified for orphan drugs were: "disease severity", "unmet needs" and "comparative effectiveness", while the "size of the population" had the lowest relevance for decision making. Test-retest analysis showed weight consistency among techniques, supporting reliability overtime. CONCLUSIONS: MCDA (EVIDEM framework) could be a useful tool to complement the current evaluation methods of CatSalut, contributing to standardization and pragmatism, providing a method to tackle ethical dilemmas and facilitating discussions related to decision making.

UNDERSTANDING VARIATIONS IN RELATIVE EFFECTIVENESS: A HEALTH PRODUCTION APPROACH.

BACKGROUND: Relative effectiveness has become a key concern of health policy. In Europe, this is because of the need for early information to guide reimbursement and funding decisions about new medical technologies. However, ways that effectiveness (does it work?) and efficacy (can it work?) might differ across health systems are poorly understood. METHODS: This study proposes an analytical framework, drawing on production function theory, to systematically identify and quantify the determinants of relative effectiveness and sources of variation between populations and healthcare systems. We consider how methods such as stochastic frontier analysis and data envelopment analysis using a Malmquist productivity index could in principle be used to generate evidence on, and improve understanding about, the sources of variation in relative effectiveness between countries and over time. RESULTS: Better evidence on factors driving relative effectiveness could: inform decisions on how to best use a new technology to maximum effectiveness; establish the need if any for follow-up post-launch studies, and provide evidence of the impact of new health technologies on outcomes in different healthcare systems. CONCLUSIONS: The health production function approach for assessment of relative effectiveness is complementary to traditional experimental and observational studies, focusing on identifying, collecting, and analyzing data at the national level, enabling comparisons to take place. There is a strong case for exploring the use of this approach to better understand the impact of new medicines and devices for improvements in health outcomes.

RELATIVE EFFECTIVENESS IN BREAST CANCER TREATMENT: A HEALTH PRODUCTION APPROACH.

BACKGROUND: Pharmaceuticals' relative effectiveness has come to the fore in the policy arena, reflecting the need to understand how relative efficacy (what can work) translates into added benefit in routine clinical use (what does work). European payers and licensing authorities assess value for money and post-launch benefit-risk profiles, and efforts to standardize assessments of relative effectiveness across the European Union (EU) are under way. However, the ways that relative effectiveness differs across EU healthcare settings are poorly understood. METHODS: To understand which factors influence differences in relative effectiveness, we developed an analytical framework that treats the healthcare system as a health production function. Using evidence on breast cancer from England, Spain, and Sweden as a case study, we investigated the reasons why the relative effectiveness of a new drug might vary across healthcare systems. Evidence was identified from a literature review and national clinical guidance. RESULTS: The review included thirteen international studies and thirty country-specific studies. Cross-country differences in population age structure, deprivation, and educational attainment were consistently associated with variation in outcomes. Screening intensity appeared to drive differences in survival, although the impact on mortality was unclear. CONCLUSIONS: The way efficacy translates into relative effectiveness across health systems is likely to be influenced by a range of complex and interrelated factors. These factors could inform government and payer policy decisions on ways to optimize relative effectiveness, and help increase understanding of the potential transferability of data on relative effectiveness from one health system to another.

Cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% in the treatment of actinic keratosis in Spain.

OBJECTIVE: The aim of this study is to conduct a cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain. METHODS: An analytical decision-making model was constructed to compare whether 5-FU/SA was a cost-effective option compared with cryotherapy from the perspective of the Spanish National Health System with a time horizon of 6 months. Costs were expressed in 2014 euros. RESULTS: The cost of patients with hyperkeratotic actinic keratosis treated with 5-FU/SA or cryotherapy was €266 and €285, respectively. 5-FU/SA was associated with higher rates of treatment success and, consequently, more quality-adjusted life years, than cryotherapy. Therefore, 5-FU/SA was the dominant treatment, as it was associated with a lower treatment cost and greater effectiveness than cryotherapy. CONCLUSIONS: Economically, 5-FU/SA was a dominant option compared with cryotherapy in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain.

Projecting expenditure on medicines in the UK NHS.

BACKGROUND: Expenditure on medicines is a readily identifiable element of health service costs. It is the focus of much attention by payers, not least in the UK even though the cost of medicines represents less than 10 % of total UK National Health Service (NHS) expenditure. Projecting future medicines spending enables the likely cost pressure to be allowed for in planning the scale and allocation of NHS resources. Simple extrapolations of past trends in expenditure fail to account for changes in the rate and mix of new medicines becoming available and in the scope for windfall savings when some medicines lose their patent protection. The objective of this study is to develop and test an improved method to project NHS pharmaceutical expenditure in the UK for the period 2012-2015. METHODS: We have adopted a product-by-product, bottom-up approach, which means that our projections are built up from individual products to the total market. Our projections of the impact of generic and biosimilars entry on prices and quantities of medicines sold, and of the rate of uptake of newly launched medicines, have been obtained from regression analysis of UK data. To address uncertainty, we have created a baseline and two other illustrative scenarios. We have compared our projections with actual expenditure for 2012. RESULTS: Our projections estimate that, between 2011 and 2015, with no change in policy or price regulation, the UK total medicines bill would increase at an average compound annual growth rate (CAGR) of between 3.1 and 4.1 %. Total NHS spending on branded medicines and total NHS spending on generics are projected to increase at average CAGRs of 0.5-1.8 and 10.0-11.0 %, respectively, over the same time period. For the total market, the actual growth rate for 2012 lay within our projected range. CONCLUSIONS: Our methodology provides a useful framework for projecting UK NHS medicines expenditure over the medium term and captures the impacts of existing medicines losing exclusivity and of new medicines being launched onto the market.

Cost analysis of the treatments for patients with advanced Parkinson's disease: SCOPE study.

OBJECTIVE: To perform a comparative long-term analysis of the associated healthcare costs for the therapeutic options in advanced Parkinson's Disease (PD): deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa infusion (CDLCI), and continuous subcutaneous apomorphine infusion (CSAI). METHODS: Resource use associated with the pre-treatment period, procedure, and follow-up was assessed for the three therapies from the perspective of the Spanish national healthcare system. Resources consumption was measured with a Healthcare Resources Questionnaire (at nine advanced PD centres). Unit costs (Euro-Spain 2010) were applied to measure resource use to obtain the average total cost for each therapy over 5 years. RESULTS: Mean cumulative 5-year cost per patient was significantly lower with DBS (€88,014) vs CSAI (€141,393) and CDLCI (€233,986) (p < 0.0001). DBS was associated with the lowest cumulative costs from year 2, with a yearly average cost of €17,603 vs €46,797 for CDLCI (p = 0.001) and €28,279 for CSAI (p = 0.008). For every patient treated annually with CDLCI, two could be treated with DBS (or €29,194 could be saved) and for every patient treated with CSAI, €10,676 could be saved with DBS. The initial DBS investment (32.2% of the total 5-year costs) was offset by decreases in anti-Parkinsonian drugs and follow-up costs. CDLCI and CSAI required constant drug use (i.e., levodopa and carbidopa for CDLCI, apomorphine for CSAI), representing ∼95% of their total 5-year cost. LIMITATIONS: All costs were based on a questionnaire, not on actual clinical data. The study is not a cost-effectiveness analysis as there is a lack of comparable outcomes data. An expert panel was used due to the complexity and variability in the treatment of advanced PD. The sample size was relatively small. CONCLUSIONS: Overall, DBS requires less use of health resources than CDLCI or CSAI in advanced PD patients, mostly pharmacological. The initial DBS investment was offset at year 2 by reductions in the ongoing consumption of anti-Parkinsonian medication. For every patient treated annually with CDLCI or CSAI, substantial cost savings could be made with DBS.