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Background and ObjectivesAbaloparatide (ABL) significantly increases bone mineral density in men with osteoporosis similar to what was reported in postmenopausal women with osteoporosis. The cost effectiveness of sequential treatment with ABL followed by alendronate (ALN) in men at high fracture risk was compared to relevant alternative treatments.MethodsA Markov-based microsimulation model based on a lifetime US healthcare decision maker perspective was developed to evaluate the cost (expressed in US$2021) per quality-adjusted life-years (QALYs) gained of sequential ABL/ALN. Comparators were sequential treatment unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Discount rates of 3% were used. Consistent with practice guidelines, patients received 18 months of ABL or TPTD followed by ALN for 5 years, or 5 years of ALN monotherapy. Analyses were conducted in high-risk men aged over 50 years defined as having a bone mineral density T-score = 60 years.ConclusionsSequential therapy using ABL/ALN may be cost effective compared with generic ALN monotherapy in US men aged >= 50 years at high fracture risk, especially in those aged >= 60 years. Unbranded TPTD/ALN and no treatment were dominated interventions (less QALY, more costs) compared with ABL/ALN or ALN monotherapy.

Background The promotion of healthy lifestyles has high priority on the global public health agenda. Evidence on the real-world (cost-)effectiveness of policies addressing nutrition and physical activity is needed. To estimate short-term policy impacts, quasi-experimental methods using observational data are useful, while simulation models can estimate long-term impacts. We review the methods, challenges and potential synergies of both approaches for the evaluation of nutrition and physical activity policies. Methods We performed an integrative review applying purposive literature sampling techniques to synthesize original articles, systematic reviews and lessons learned from public international workshops conducted within the European Union Policy Evaluation Network. Results We highlight data requirements for policy evaluations, discuss the distinct assumptions of instrumental variable, difference-in-difference, and regression discontinuity designs and describe the necessary robustness and falsification analyses to test them. Further, we summarize the specific assumptions of comparative risk assessment and Markov state-transition simulation models, including their extension to microsimulation. We describe the advantages and limitations of these modelling approaches and discuss future directions, such as the adequate consideration of heterogeneous policy responses. Finally, we highlight how quasi-experimental and simulation modelling methods can be integrated into an evidence cycle for policy evaluation. Conclusions Assumptions of quasi-experimental and simulation modelling methods in policy evaluations should be credible, rigorously tested and transparently communicated. Both approaches can be applied synergistically within a coherent framework to compare policy implementation scenarios and improve the estimation of nutrition and physical activity policy impacts, including their distribution across population sub-groups.

Nitric oxide is a gas produced in the airways of asthmatic subjects and related to T2 inflammation. It can be measured as fractional nitric oxide (FeNO) in the exhaled air and used as a non-invasive, easy to evaluate, rapid marker. It is now widely used in many settings to determine airway inflammation. The aim of this narrative review is to report relationship between FeNO and the physiopathologic characteristics of asthmatic patients. Factors affecting FeNO levels have also been analysed as well as the impact of corticosteroid, target therapies and rehabilitation programs. Considering the availability of the test, spreading this method-ology to low income countries has also been considered as a possibility for evaluating airway inflammation and monitoring adherence to inhaled corticosteroid therapy. PubMed data search has been performed restricted to English language papers. Research was limited to studies in adults unless studies in children were the only ones reported for a particular issue. This revision could be useful to summarize the role of FeNO in relation to asthma charac-teristics and help in the use of FeNO in different clinical settings particularly in low income countries. (c) 2020 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Nitric oxide is a gas produced in the airways of asthmatic subjects and related to T2 inflammation. It can be measured as fractional nitric oxide (FeNO) in the exhaled air and used as a non-invasive, easy to evaluate, rapid marker. It is now widely used in many settings to determine airway inflammation. The aim of this narrative review is to report relationship between FeNO and the physiopathologic characteristics of asthmatic patients. Factors affecting FeNO levels have also been analysed as well as the impact of corticosteroid, target therapies and rehabilitation programs. Considering the availability of the test, spreading this method-ology to low income countries has also been considered as a possibility for evaluating airway inflammation and monitoring adherence to inhaled corticosteroid therapy. PubMed data search has been performed restricted to English language papers. Research was limited to studies in adults unless studies in children were the only ones reported for a particular issue. This revision could be useful to summarize the role of FeNO in relation to asthma charac-teristics and help in the use of FeNO in different clinical settings particularly in low income countries. (c) 2020 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Objectives Survival extrapolation of trial outcomes is required for health economic evaluation. Generally, all-cause mortality (ACM) is modeled using standard parametric distributions, often without distinguishing disease-specific/excess mortality and general population background mortality (GPM). Recent National Institute for Health and Care Excellence guidance (Technical Support Document 21) recommends adding GPM hazards to disease-specific/excess mortality hazards in the log-likelihood function (“internal additive hazards”). This article compares alternative extrapolation approaches with and without GPM adjustment. Methods Survival extrapolations using the internal additive hazards approach (1) are compared to no GPM adjustment (2), applying GPM hazards once ACM hazards drop below GPM hazards (3), adding GPM hazards to ACM hazards (4), and proportional hazards for ACM versus GPM hazards (5). The fit, face validity, mean predicted life-years, and corresponding uncertainty measures are assessed for the active versus control arms of immature and mature (30- and 75-month follow-up) multiple myeloma data and mature (64-month follow-up) breast cancer data. Results The 5 approaches yielded considerably different outcomes. Incremental mean predicted life-years vary most in the immature multiple myeloma data set. The lognormal distribution (best statistical fit for approaches 1-4) produces survival increments of 3.5 (95% credible interval: 1.4-5.3), 8.5 (3.1-13.0), 3.5 (1.3-5.4), 2.9 (1.1-4.5), and 1.6 (0.4-2.8) years for approaches 1 to 5, respectively. Approach 1 had the highest face validity for all data sets. Uncertainty over parametric distributions was comparable for GPM-adjusted approaches 1, 3, and 4, and much larger for approach 2. Conclusion This study highlights the importance of GPM adjustment, and particularly of incorporating GPM hazards in the log-likelihood function of standard parametric distributions.

Background A recently conducted matching-adjusted indirect comparison demonstrated that bosutinib improved progression-free survival, and delayed progression to advanced disease compared with dasatinib and nilotinib in patients with second line (2L) chronic-phase chronic myeloid leukemia (CP-CML). However, the long-term clinical and economic impact of using bosutinib versus dasatinib and nilotinib has not been evaluated. The objective was to determine the cost-effectiveness of bosutinib compared with dasatinib and bosutinib compared with nilotinib from a US payer perspective. Methods A cost-effectiveness model was developed using partition survival methods and three health states: progression-free, progression, and death. Trial data (individual patient-level and aggregate-level data) informed the progression-free and overall survival estimates. Costs included drugs and medical resource use. Utility values were obtained from literature. Sensitivity analyses (SAs) included one-way and probabilistic sensitivity analyses (PSAs). Results Comparing bosutinib versus dasatinib resulted in a gain of 0.4 discounted life years, 1.5 quality-adjusted life years (QALYs), and incremental costs of $28,459 (values in 2020 US dollars), for an incremental cost-effectiveness ratio (ICER) of $19,811/QALY gained. Comparing bosutinib versus nilotinib resulted in a gain of 0.8 discounted life-years, 1.8 QALYs, and incremental costs of $76,563, for an ICER of $41,932/QALY gained. Drug costs and extrapolation distribution type were the main drivers of the model in the one-way SAs. In the PSAs, bosutinib had >90% and >80% probabilities of being cost-effective at a willingness-to-pay threshold of $100,000/QALY versus dasatinib and nilotinib, respectively. Conclusions Our results suggest that compared with dasatinib and nilotinib, bosutinib may represent good value for money for treating 2L CP-CML patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40258-021-00666-0.

Background The evidence used to inform health care decision making (HCDM) is typically uncertain. In these situations, the experience of experts is essential to help decision makers reach a decision. Structured expert elicitation (referred to as elicitation) is a quantitative process to capture experts’ beliefs. There is heterogeneity in the existing elicitation methodology used in HCDM, and it is not clear if existing guidelines are appropriate for use in this context. In this article, we seek to establish reference case methods for elicitation to inform HCDM. Methods We collated the methods available for elicitation using reviews and critique. In addition, we conducted controlled experiments to test the accuracy of alternative methods. We determined the suitability of the methods choices for use in HCDM according to a predefined set of principles for elicitation in HCDM, which we have also generated. We determined reference case methods for elicitation in HCDM for health technology assessment (HTA). Results In almost all methods choices available for elicitation, we found a lack of empirical evidence supporting recommendations. Despite this, it is possible to define reference case methods for HTA. The reference methods include a focus on gathering experts with substantive knowledge of the quantities being elicited as opposed to those trained in probability and statistics, eliciting quantities that the expert might observe directly, and individual elicitation of beliefs, rather than solely consensus methods. It is likely that there are additional considerations for decision makers in health care outside of HTA. Conclusions The reference case developed here allows the use of different methods, depending on the decision-making setting. Further applied examples of elicitation methods would be useful. Experimental evidence comparing methods should be generated.

Background: The health economic literature has questioned the cost-effectiveness and affordability of advanced therapies, proposed adjustments to value assessment frameworks, and discussed the use of outcome-based managed entry agreements and staggered payments in the last few years. The aim of this manuscript is to conduct a critical reflection on assessment criteria and access conditions for reimbursement of advanced therapies.Methods: A narrative review of the peer-reviewed literature and grey literature was conducted in April 2021 by searching PubMed; Google Scholar; policy and legislative documents; websites of health technology assessment agencies, advanced therapy organisations, governmental advanced therapy innovation programmes, consultancy agencies; ISPOR conference abstracts and presentations.Results: Based on the available evidence, this manuscript argues that: a) advanced therapies can be cost-effective at high prices set by manufacturers; b) the economic evaluation framework adopted by many payers under-values these products; c) advanced therapies can be affordable and may not require spread payments; d) outcome-based managed entry agreements are theoretically attractive, but challenging in practice; e) the cost-effectiveness of advanced therapies depends on the outcome-based managed entry agreement and payment approach; f) there is a role for multinational collaborations to manage reimbursement and access of advanced therapies.Conclusions: This manuscript shows that there is no single approach to reimbursement and access of advanced therapies. Instead, we support a more tailored assessment of health economic aspects of advanced therapies, which considers the heterogeneity of these products and their target populations.

Background Health Technology Assessment (HTA), which can support public drug reimbursement decisions will play a core function in the planned national Pharmacare program in Canada. To address existing barriers to the use of HTA, these must be ranked in order of priority. The goal of this study was to access the relative importance of known facilitators and barriers to the use of HTA in the context of the Canadian health care system, with attention to differences between regions and stakeholder groups. Methods We used the best-worst scaling object case approach to elicit a quantitative ranking of a list of 20 facilitators and 22 barriers. A sample of 68 Canadian HTA stakeholders, including members of expert committees, decision/policymakers, researchers/academics, and others participated in the study. Their task was to identify the most important and the least important item in 12 sub-sets of five facilitators and 14 sub-sets of five barriers. Findings Relative Importance Scores derived via hierarchical Bayes analysis revealed relations, engagement, and contact between stakeholders as most important on both the barrier and facilitator sides. Other top-ranked facilitators included the availably of credible and relevant research. Other top-ranked barriers included inconsistencies in the evidence and limited generalizability. The availability of HTA guidelines did not rank highly on either side. The main limitation of the study was the challenge with reaching the relevant respondents; this was mitigated by involving the national HTA agency in the research. Conclusion Canadian stakeholders consider the relationships within the HTA network among the most important. Policies should focus on strengthening these relationships. Future research should focus on the connectivity and distribution of knowledge and power within the HTA network.

Food policies for the prevention and management of diet-related non-communicable diseases (NCDs) have been increasingly relying on microsimulation models (MSMs) to assess effectiveness. Given the increased uptake of MSMs, this review aims to provide an overview of the characteristics of MSMs that link diets with NCDs. A comprehensive review was conducted in PubMed and Web of Knowledge. Inclusion criteria were: (i) findings from a MSM, (ii) diets, foods or nutrients as main exposure of interest, (iii) NCDs, such as overweight/obesity, type 2 diabetes, coronary heart disease, stroke or cancer as disease outcome for impact assessment. This review included information from 33 studies using MSM in analyzing diet and diverse food policies on NCDs. Hereby, most models employed stochastic, discrete-time, dynamic microsimulation techniques to calculate anticipated (cost-)effectiveness of strategies based on food pricing, food reformulation or dietary (lifestyle) interventions. Currently available models differ in the methodology used for quantifying the effect of the dietary changes on disease, and in the method for modelling disease incidence and mortality. However, all studies provided evidence that the models were sufficiently capturing the close-to-reality situation by justifying their choice of model parameters and validating externally their modelled disease incidence and mortality with observed or predicted event data. With the increasing use of various MSMs, between-model comparisons, facilitated by open access models and good reporting practices, would be important for judging model's accuracy, leading to continued improvement in the methodologies for developing and applying MSMs, and subsequently a better understanding of the results by policymakers. A statement of significance Given the advancement in the application of microsimulation modelling in evaluating food policies and measuring diet-related disease burdens, the present scoping review serves as an exercise to inform future modelling, hereby highlighting the need for transparency in model development, application and dissemination to advance and safeguard accuracy and relevance in modelling efforts.

Improving the efficiency of mental healthcare service delivery by learning from international best-practice examples requires valid data, including robust unit costs, which currently often lack cross-country comparability. The European ProgrammE in Costing, resource use measurement and outcome valuation for Use in multi-sectoral National and International health economic evaluAtions (PECUNIA) aimed to harmonize the international unit cost development. This article presents the methodology and set of 36 externally validated, standardized reference unit costs (RUCs) for five health and social care services (general practitioner, dentist, help-line, day-care center, nursing home) in Austria, England, Germany, Hungary, The Netherlands, and Spain based on unambiguous service definitions using the extended DESDE PECUNIA coding framework. The resulting PECUNIA RUCs are largely comparable across countries, with any causes for deviations (e.g., country-specific scope of services) transparently documented. Even under standardized methods, notable limitations due to data-driven divergences in key costing parameters remain. Increased cross-country comparability by adopting a uniform methodology and definitions can advance the quality of evidence-based policy guidance derived from health economic evaluations. The PECUNIA RUCs are available free of charge and aim to significantly improve the quality and feasibility of future economic evaluations and their transferability across mental health systems.

Summary Background Actinic keratosis (AK) is a common premalignant skin condition that might have the ability to progress into squamous cell carcinoma. Due to the high incidence of AK, treatment of this disease significantly impacts healthcare spending. Objectives To determine which commonly prescribed field‐directed treatment is the most cost‐effective, when comparing 5‐fluorouracil (5‐FU) 5%, imiquimod (IMQ) 5%, ingenol mebutate (IM) 0·015% and methyl aminolaevulinate photodynamic therapy (MAL‐PDT) for AK in the head and neck region. Methods We performed an economic evaluation from a healthcare perspective. Data were collected alongside a single‐blinded, prospective, multicentre randomized controlled trial with 624 participants in the Netherlands. The outcome measure was expressed as the incremental cost‐effectiveness ratio, which is the incremental costs per additional patient with ≥ 75% lesion reduction compared with baseline. This trial was registered at ClinicalTrials.gov, number NCT02281682. Results The trial showed that 5‐FU was the most effective field treatment for AK in the head and neck region. Twelve months post‐treatment, the total mean costs for 5‐FU were significantly lower (€433) than the €728, €775 and €1621 for IMQ, IM and MAL‐PDT, respectively. The results showed that 5‐FU was a dominant cost‐effective treatment (more effective and less expensive) compared with the other treatments, 12 months post‐treatment. Conclusions Based on these results, we consider 5‐FU 5% cream as the first‐choice treatment option for multiple AKs in the head and neck area. What's already known about this topic? Due to the increasing incidence of actinic keratosis (AK), the recommended treatment results in a considerable socioeconomic burden for (dermatological) healthcare.Although cost‐effectiveness modelling studies have been performed in which different treatments for AK were compared, a prospective clinical trial comparing four frequently prescribed treatments on effectiveness and resource consumption within a time horizon of 12 months has never been conducted. What does this study add? This is the first study examining the cost‐effectiveness of 5‐fluorouracil 5% cream, imiquimod 5% cream, ingenol mebutate 0·015% gel and methyl aminolaevulinate photodynamic therapy, with data collected in a randomized controlled trial over a time horizon of 12 months.We found that 5‐fluorouracil was a dominant cost‐effective treatment (more effective and less costly), based on data from the Netherlands. Linked Comment: Steeb et al. Br J Dermatol 2020; 183:612., Linked Comment: Steeb et al. Br J Dermatol 2020; 183:612. Plain language summary available online

Background New pharmacological therapies for the treatment of cardiovascular disease (CVD) have emerged in recent years. The high rates of CVD and the need for long-term treatment to decrease risk factors makes cost-effectiveness crucial for their successful long-term implementation. Objective This study assessed cost-effectiveness studies of novel pharmacological treatments (ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, omega-3 polyunsaturated fatty acids [n-3 PUFAs], and the cardiovascular polypill) compared with standard care for the secondary prevention of CVD. Methods We searched seven databases and the reference list of selected literature reviews for eligible cost-effective analyses (CEA) published between January 2009 and January 2020 that evaluated the above novel treatments versus standard care. Two independent reviewers performed the screening and evaluation in accordance with the Consolidated Health Economic Evaluation Reporting Standards statement. Cost results were adapted to 2018 US dollars (US$) to facilitate comparisons between studies. Consideration of cost-effectiveness was based on the original study criteria. Results Thirty-two studies were included in this review, most of them adopting a healthcare perspective. Studies evaluating ezetimibe, PCSK9 inhibitors and n-3 PUFAs assessed their addition to standard care compared with standard care alone, while studies analysing the polypill evaluated the replacement of multiple monotherapies for a fixed-dose combination. Ten studies reported on ezetimibe, fifteen evaluated PCSK9 inhibitors, five focused on n-3 PUFAs and seven on the polypill. From a healthcare perspective, ezetimibe was cost effective in 62.5% of the studies (incremental cost-effectiveness ratios [ICERs] ranged from US$27,195 to US$204,140), n-3 PUFAs in 60% (ICERs from US$57,128 to US$139,082) and the cardiovascular polypill in 100% (ICERs from dominant to US$30,731) compared with standard care. Conversely, only 10% of the studies considered PCSK9 inhibitors cost effective compared with standard care from a healthcare perspective (ICERs ranged from US$231,119 to US$1,223,831). Additionally, ezetimibe was cost effective in 50% of the studies, PCSK9 inhibitors in 33% and the polypill in 50% of the studies adopting a societal perspective. The key model-related parameters predicting cost-effectiveness included drug cost, time horizon, and the baseline risk of cardiovascular events. Conclusions Based on current pricing and willingness-to-pay thresholds, most CEA studies considered ezetimibe, n-3 PUFAs and the polypill to be cost effective compared with standard care but not PCSK9 inhibitors for secondary prevention of CVD.

Background: Falls are an increasing problem among older people. There are several evidence-based interventions available to prevent falls. However, these are not always well implemented in the primary care setting. General practitioners (GPs) are often the first point of contact for health issues, making them the designated professionals for providing falls prevention. Because GPs are often unaware which patients have a high fall risk and patients themselves do not always know they have a high fall risk, this study aims to evaluate the implementation of a targeted fall risk screening strategy among independently living, frail older people in the primary care setting. Materials and methods: The targeted fall risk screening strategy used in this study consists of tools for screening high fall risk and for identifying the underlying cause(s) of the high fall risk, an accredited training course in falls prevention for professionals, and service provision by certified physio- and exercise therapists who are able to offer evidence-based falls prevention interventions. This targeted fall risk screening strategy will be implemented in the primary care setting and evaluated at the level of the GP practice and at the level of the patient by using the RE-AIM model of Glasgow et al. In a pre-posttest design, data will be collected of the total number of frail older people who are screened, referred and enrolled for fall-preventive care. Furthermore, barriers and facilitators of the implementation of the fall risk screening strategy will be identified by conducting focus groups and interviews with the care providers and frail older patients. Additionally, the influence of the falls prevention interventions on frail older patients will be evaluated by using a pre-posttest design with a 12-month follow-up period during which data are collected regarding patients' stability, mobility, strength, balance, self-efficacy, health status, and daily activities. Study Registration: This study is approved by the Medical Ethics Committee Brabant, the Netherlands (NL61582.028.17/ P1732) and registered at the Netherlands Trial Register, NL7917.

Evaluations are considered of key importance for a well-functioning democracy. Against this background, it is vital to assess whether and how evaluation models approach the role of citizens. This paper is the first in presenting a review of citizen involvement in the main evaluation models which are commonly distinguished in the field. We present the results of both a document analysis and an international survey with experts who had a prominent role in developing the models. This overview has not only a theoretical relevance, but can also be helpful for evaluation practitioners or scholars looking for opportunities for citizen involvement. The paper contributes to the evaluation literature in the first place, but also aims to fine-tune available insights on the relationship between evidence informed policy making and citizens. ispartof: American Journal Of Evaluation status: Published online

Objectives: Studies on variability drivers of treatment costs in hospitals can provide the necessary information for policymakers and healthcare providers seeking to redesign reimbursement schemes and improve the outcomes-over-cost ratio, respectively. This systematic literature review, focusing on the hospital perspective, provides an overview of studies focusing on variability in treatment cost, an outline of their study characteristics and cost drivers, and suggestions on future research methodology. Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Handbook for Systematic Reviews of Interventions. We searched PubMED/MEDLINE, Web of Science, EMBASE, Scopus, CINAHL, Science direct, OvidSP and Cochrane library. Two investigators extracted and appraised data for citation until October 2020. Results: 90 eligible articles were included. Patient, treatment and disease characteristics and, to a lesser extent, outcome and institutional characteristics were identified as significant variables explaining cost variability. In one-third of the studies, the costing method was classified as unclear due to the limited explanation provided by the authors. Conclusion: Various patient, treatment and disease characteristics were identified to explain hospital cost variability. The limited transparency on how hospital costs are defined is a remarkable observation for studies wherein cost variability is the main focus. Recommendations relating to variables, costs, and statistical methods to consider when designing and conducting cost variability studies were provided. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Due to the threat of climate change, renewable feedstocks & alternative energy carriers are becoming more necessary than ever. One key vector is hydrogen, which can fulfil these roles and is a renewable resource when split from water using renewable electricity. Electrolyzers are often not designed for variable operation, such as power from sources like wind or solar. This work develops a framework to optimize the design and operation of a large-scale electrolyzer hub under variable power supply. The framework is a two-part optimization, where designs of repeated, modular units are optimized, then the entire system is optimized based on those modular units. The framework is tested using a case study of an electrolyzer hub powered by a Dutch wind farm to minimize the levelized cost of hydrogen. To understand how the optimal design changes, three power profiles are examined, including a steady power supply, a representative wind farm power supply, and the same wind farm power supply compressed in time. The work finds the compressed power profile uses PEM technology which can ramp up and down more quickly. The framework determines for this case study, pressurized alkaline electrolyzers with large stacks are the cheapest modular unit, and while a steady power profile resulted in the cheapest hydrogen, costing 4.73 €/kg, the typical wind power profile only raised the levelized cost by 2%–4.82 €/kg. This framework is useful for designing large-scale electrolysis plants and understanding the impact of specific design choices on the performance of a plant.

The most appropriate next step in depression treatment after the initial treatment fails is unclear. This study explores the suitability of the Markov decision process for optimizing sequential treatment decisions for depression. We conducted a formal comparison of a Markov decision process approach and mainstream state-transition models as used in health economic decision analysis to clarify differences in the model structure. We performed two reviews: the first to identify existing applications of the Markov decision process in the field of healthcare and the second to identify existing health economic models for depression. We then illustrated the application of a Markov decision process by reformulating an existing health economic model. This provided input for discussing the suitability of a Markov decision process for solving sequential treatment decisions in depression. The Markov decision process and state-transition models differed in terms of flexibility in modeling actions and rewards. In all, 23 applications of a Markov decision process within the context of somatic disease were included, 16 of which concerned sequential treatment decisions. Most existing health economic models relating to depression have a state-transition structure. The example application replicated the health economic model and enabled additional capacity to make dynamic comparisons of more interventions over time than was possible with traditional state-transition models. Markov decision processes have been successfully applied to address sequential treatment-decision problems, although the results have been published mostly in economics journals that are not related to healthcare. One advantage of a Markov decision process compared with state-transition models is that it allows extended action space: the possibility of making dynamic comparisons of different treatments over time. Within the context of depression, although existing state-transition models are too basic to evaluate sequential treatment decisions, the assumptions of a Markov decision process could be satisfied. The Markov decision process could therefore serve as a powerful model for optimizing sequential treatment in depression. This would require a sufficiently elaborate state-transition model at the cohort or patient level.

Neily Zakiyah,1,2 Rano K Sinuraya,1– 3 Arif SW Kusuma,2,4 Auliya A Suwantika,1,2,5 Keri Lestari1,2 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 2Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia; 3Unit of Global Health, Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; 4Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 5Center for Health Technology Assessment, Universitas Padjadjaran, Bandung, 40132, IndonesiaCorrespondence: Neily Zakiyah Tel/Fax +62 22-7796200Email neily.zakiyah@unpad.ac.idObjective: Sacubitril/valsartan is a relatively new medication that is more effective than the usual enalapril for heart failure patients with reduced ejection fraction. Therefore, this study aims to determine the cost-effectiveness of sacubitril/valsartan compared to enalapril in Indonesia’s healthcare system.Methods: In this study, a Markov decision-analytic model was developed to estimate the total cost, health outcomes, and cost-effectiveness of sacubitril/valsartan compared to enalapril from Indonesia’s healthcare perspective. The input parameters for the cost-effectiveness were predominantly from the PARADIGM-HF trial. Subsequently, the country-specific data were synthesized for medication and hospitalization costs, cardiovascular and non-cardiovascular death, as well as re-hospitalization rate. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) gained was estimated to determine the cost-effectiveness. Deterministic and probabilistic sensitivity analyses were conducted to assess the impact of parameter uncertainty.Results and Discussion: In the base case, sacubitril/valsartan was more costly and effective than enalapril with a total cost of IDR 91,783,325,865 (USD 6,487,522) vs IDR 68,101,971,241 (USD 4,813,653) and a total QALYs of 19,680 vs 18,795, resulting in an ICER of IDR 26,742,098 (USD 1890). Based on the willingness to pay threshold GDP per capita in Indonesia, it can be considered cost-effective. The most influential drivers of cost-effectiveness in deterministic sensitivity analysis were risk of mortality outside hospitalization, hospital admission rate, and cost of sacubitril/valsartan. The vast majority of simulation results from probabilistic analysis suggested that sacubitril/valsartan was likely resulted in higher cost and improved QALYs compared with enalapril, indicating the robustness of the model.Conclusion: Based on the current price in Indonesia, sacubitril/valsartan can be considered a cost-effective option, although this depends heavily on the willingness to pay threshold. Further studies that incorporate real-world evidence with sacubitril/valsartan are needed to inform the decision-making process.Keywords: cost-effectiveness, heart failure, Markov model, sacubitril/valsartan

Objectives There is emerging evidence supporting sequential therapy with an osteoanabolic followed by an antiresorptive in patients at high-risk of fragility fractures. This study assessed the cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) [(ABL/ALN)] compared with teriparatide (TPTD) followed by ALN (TPTD/ALN). Methods A previously validated Markov microsimulation model was adapted to estimate the cost-effectiveness of sequential ABL/ALN compared with sequential TPTD/ALN and no treatment with a lifetime horizon from the US payer perspective. Patients were assumed to receive ABL or TPTD for 18 months followed by 5 years of ALN in line with clinical recommendations. The effects of ABL on fracture risk were derived from the ACTIVExtend trial. The effects of TPTD were assumed to be maintained during subsequent ALN treatment, consistent with ACTIVExtend findings for ABL. Evaluation was completed for patients, aged 50–80 years with a BMD T-score ≤ −3.5 or with a T-score between −2.5 and −3.5 and a history of ≥ one osteoporotic fracture. Results In all simulated populations, sequential ABL/ALN therapy was dominant (lower costs, higher QALYs) compared with sequential TPTD/ALN therapy, resulting from the improved efficacy and lower drug price of ABL. Probabilistic sensitivity analyses suggested that ABL/ALN was dominant in at least 99% of the simulations. Compared to no treatment, the cost per QALY gained of ABL/ALN was always below $130,000. Conclusions Sequential ABL/ALN therapy is a cost-effective (dominant) strategy compared with sequential TPTD/ALN therapy for the treatment of US women at increased risk of fractures.

BACKGROUND: Health economic evaluations are often required before implementing a vaccination programme. Such evaluations rarely consider the historical context of a vaccination programme. We review the financial history of vaccination programmes in the Netherlands, and compare these to demographic and macroeconomic developments as well as avoided mortality burden.METHODS: Previously uncatalogued historical expenditures on the Dutch National Immunisation Programme (NIP) and influenza vaccination were obtained from official reports. Costs were adjusted for inflation using Consumer Price Indices and expressed in Euro of 2016. Estimates on mortality burden averted were obtained from previous research and used to calculate the ratio of expenses to averted mortality burden for vaccinations against diphtheria, tetanus, pertussis, polio, measles, mumps and rubella for birth cohorts 1953-1992.RESULTS: Developments towards a uniform government funded NIP started early 1950s with vaccinations against diphtheria, pertussis and tetanus, culminating in its official launch in 1957 together with polio vaccinations. Since the 1980s, expenditure increased nearly five-fold mostly due to the addition of new vaccines, while spending on already implemented vaccinations tended to decline. Overall, expenditure increased from € 5 million in 1957 to € 93 million in 2014. Relative to total healthcare expenditure, the NIP contributed little, ranging between 0.05% and 0.14%. Spending on influenza vaccination increased from € 37 million in 1996 to € 52 million in 2014, while relative to total healthcare expenditure it decreased from 0.069% to 0.055%. In 2014, 0.15% of healthcare expenditure and € 533 per birth was spent on vaccination programmes. Overall, for birth cohorts 1953-1992, € 5.4 thousand (95% confidence interval: 4.0-7.3) was expended per year-of-life-lost averted.CONCLUSION: The actual costs per year-of-life gained are more favorable than estimated here since averted medical costs were not included. Although expenditure on vaccination programmes increased substantially, the contribution to overall healthcare expenditure remained small.

Objectives: To determine how the value of new medicines is defined from the perspective of different stakeholders in nine European countries. Methods: We carried out an explorative survey by conducting in-depth qualitative interviews with a range of experts with health technology assessment, clinical provision, health economics, payer, academic and industry experience. Experts were asked to distribute 100 points over a predefined list of attributes related to value. In total, 30 interviews were conducted with seven academics, five clinicians, nine economists, five payers and four providers. Each of these categories was represented in responses from France, Germany, the Netherlands and the UK. Results: Comments on the interview guide were all positive. There was substantial variation in definitions of value provided by respondents. Most respondents indicated that delivering benefits to the patient is a prerequisite for a healthcare product to be of value, but only half included costs or resource use in their definition. Quantitative responses showed that effectiveness and efficacy were considered the most important attributes of value, followed by safety and side effects. Lower scores were given to other attributes, such as dignity and individualism, and invasiveness of the treatment. Resources and costs associated with complications and readmissions were considered important by academics and economists, but not clinicians. Conclusions: The interview findings indicate that the value of a drug is subjective in being perceived differently by different stakeholders, and for different treatment types. Future research will require evaluation of the views of a larger number of stakeholders in more and different countries to confirm these findings. © European Association of Hospital Pharmacists (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Purposes Intervention mapping (IM) is a protocol for developing effective behavior change interventions. It has been used for 10 years to develop work disability prevention (WDP) interventions, but it is not known to what extent and with what success. The main objective of this study was to review the effectiveness of these interventions. Secondary objectives were to review their fidelity to the IM protocol, their theoretical frameworks and their content. Methods A search strategy was conducted in MEDLINE, Web of Science, PsycINFO, Pascal, Francis, and BDSP. All titles and abstracts were reviewed. A standardized extraction form was developed. All included studies were reviewed by two reviewers blinded to each other. Results Eight WDP interventions were identified aimed at return to work (RTW; n = 6) and self-management at work (n = 2). RTW interventions targeted workers with stress-related mental disorders (n = 1), low back pain (n = 1), musculoskeletal disorders (n = 1), cancer (n = 2) and gynecological surgery (n = 1). The fidelity to the IM protocol was weaker for the participatory planning group. Matrices of change, change methods, and applications were systematically reported. The main theoretical frameworks used were the attitude-social influence-self efficacy model (n = 4) and the theory of planned behavior (n = 2). Half of the interventions included a workplace component (n = 4). Two interventions were reported as effective, and one partially effective. Conclusion The IM protocol is used in WDP since 2007. The participative dimension appears underused. Few theoretical frameworks were used. Implications are to better consider the stakeholders involvement, and mobilize theoretical frameworks with greater attempts to intervene on the work environment.

Summary The use of gastro-resistant risedronate, a convenient dosing regimen for oral bisphosphonate therapy, seems a cost-effective strategy compared with weekly alendronate, generic risedronate, and no treatment for the treatment of postmenopausal women with osteoporosis in France. Introduction Gastro-resistant (GR) risedronate tablets are associated with improved persistence compared to common oral bisphosphonates but are slightly more expensive. This study assessed its cost-effectiveness compared to weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France. Methods A previously validated Markov microsimulation model was used to estimate the lifetime costs (expressed in €2017) per quality-adjusted life-years (QALY) of GR risedronate compared with weekly alendronate, generic risedronate, and no treatment. Pooled efficacy data for bisphosphonates derived from a previous meta-analysis were used for all treatment options, and persistence data (up to 3 years) were obtained from a large Australian longitudinal study. Evaluation was done for high-risk women 60–80 years of age, with a bone mineral density (BMD) T-score ≤ − 2.5 and/or prevalent vertebral fractures. Results In all of the simulated populations, GR risedronate was cost-effective compared to alendronate, generic risedronate, and no treatment at a threshold of €60,000 per QALY gained. In women with a BMD T-score ≤ − 2.5 and prevalent vertebral fractures, the cost per QALY gained of GR risedronate compared to alendronate, generic risedronate, and no treatment falls below €20,000 per QALY gained. In women aged 75 years and older, GR risedronate was even shown to be dominant (more QALYs, less costs) compared to alendronate, generic risedronate, and no treatment. Conclusion This study provides the first economic results about GR risedronate, suggesting that it represents a cost-effective strategy compared with weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France.

Governments regularly have to decide whether new vaccines should be adopted in their national immunization program. These choices imply complex trade-offs of epidemiological, medical and socio-economic criteria. We investigated how the population in Flanders (Belgium) wants their government to set vaccine-funding priorities. In December 2019, we executed a discrete choice experiment in a sample of the Flemish population (N = 1636). In total, we analysed 16 360 choices between vaccines competing for funding, described in terms of eight characteristics. Using a panel mixed logit model, we quantified the relative importance of each characteristic and investigated differences in preferences across respondent groups. The observed vaccine priorities were different from those that would be identified through cost-effectiveness analysis. People valued the health impact from infectious diseases differently than their weight expressed in QALYs would suggest. Mortality and frequently occurring mild illness were valued higher, whereas lasting morbidity received lower weight. Contribution of the vaccine to disease eradication and uncertainty in vaccine effectiveness were both highly influential factors. Health equity impact was also important whereas the economic impact of the disease did not matter at all. Our results can be used to incorporate public values into vaccine decision-making. ispartof: Social Science & Medicine vol:303 ispartof: location:England status: Published online

Objective To study cost-effectiveness of an interleukin (IL)-17A inhibitor secukinumab, with other biologics and apremilast in patients with Psoriatic arthritis (PsA) from payer perspective in Finland. Methods In this semi-Markov model, subcutaneous (SC) secukinumab was compared with SC treatments etanercept and its biosimilar, certolizumab pegol, adalimumab and its biosimilar, golimumab, ustekinumab, intravenous (IV) treatment infliximab, as well as oral non-biologic apremilast. Patients without prior exposure (naïve) to biologics and without moderate to severe psoriasis were considered for secukinumab 150 mg group. Secukinumab 300 mg group included naïve patients with moderate to severe psoriasis and all patients with prior biologic exposure. The PsA Response Criteria (PsARC) at 12-week was primary criteria for treatment response. Other clinical as well as cost related model inputs were derived from relevant clinical trials as well as Finnish publications. The key model outcomes were quality-adjusted life years and incremental cost-effectiveness ratio. An annual 3% discount rate was applied to all future costs and benefits. Model input variations were assessed through sensitivity analyses and alternative scenario analyses. Results For a lifetime horizon (60 years), secukinumab 150 mg dominated all branded SC biologics and apremilast with highest QALY of 8.01 and lowest lifetime cost of €187,776, while it was cost-effective against IV infliximab among biologic-naïve patients without moderate to severe psoriasis. Secukinumab 300 mg was cost-effective against all branded SC biologics and apremilast and dominated IV infliximab among biologic-naïve patients with moderate to severe psoriasis, while it was cost-effective in biologic experienced patients. With the one-way sensitivity analysis, PsARC response, drug acquisition cost, and health assessment questionnaire score were the most important parameters affecting the outcomes. Across all treatment groups, patients on secukinumab were most likely to achieve highest net monetary benefit than other competitors in probabilistic sensitivity analysis. With alternative scenario analysis, results largely remained unchanged. Conclusions Secukinumab is a cost-effective treatment for PsA patients from a Finnish payer’s perspective. Electronic supplementary material The online version of this article (10.1186/s12962-018-0162-3) contains supplementary material, which is available to authorized users.

Neglected tropical diseases (NTDs) remain a significant cause of morbidity and mortality in many low-income and middle-income countries. Several NTDs, namely lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH) and trachoma, are predominantly controlled by preventive chemotherapy (or mass drug administration), following recommendations set by the WHO. Over one billion people are now treated for NTDs with this strategy per year. However, further investment and increased domestic healthcare spending are urgently needed to continue these programmes. Consequently, it is vital that the cost-effectiveness of preventive chemotherapy is understood. We analyse the current estimates on the cost per disability-adjusted life year (DALY) of the preventive chemotherapy strategies predominantly used for these diseases and identify key evidence gaps that require further research. Overall, the reported estimates show that preventive chemotherapy is generally cost-effective, supporting WHO recommendations. More specifically, the cost per DALY averted estimates relating to community-wide preventive chemotherapy for lymphatic filariasis and onchocerciasis were particularly favourable when compared with other public health interventions. Cost per DALY averted estimates of school-based preventive chemotherapy for schistosomiasis and STH were also generally favourable but more variable. Notably, the broader socioeconomic benefits are likely not being fully captured by the DALYs averted metric. No estimates of cost per DALY averted relating to community-wide mass antibiotic treatment for trachoma were found, highlighting the need for further research. These findings are important for informing global health policy and support the need for continuing NTD control and elimination efforts.

Background: The Dietary Approach to Stop Hypertension (DASH) and potassium supplementation have been shown to reduce the risk of death with a functioning graft (DWFG) and renal graft failure in renal transplant recipients (RTR). Unfortunately, a key problem for patients is the adherence to these diets. The aim of this study is to evaluate the cost-effectiveness and budget impact of higher adherence to either the DASH or potassium supplementation. Methods: A Markov model was used to simulate the life course of 1000 RTR in the Netherlands. A societal perspective with a lifetime time horizon was used. The potential effect of improvement of dietary adherence was modelled in different scenarios. The primary outcomes are the incremental cost-effectiveness ratio (ICER) and the budget impact. Results: In the base case, improved adherence to the DASH diet saved 27,934,786 and gained 1880 quality-adjusted life years (QALYs). Improved adherence to potassium supplementation saved €1,217,803 and gained 2901 QALYs. Both resulted in dominant ICERs. The budget impact over a five-year period for the entire Dutch RTR population was €8,144,693. Conclusion: Improving dietary adherence in RTR is likely to be cost-saving and highly likely to be cost-effective compared to the current standard of care in the Netherlands.

Background Genetic testing has potential roles in identifying whether an individual would have risk of adverse drug reactions (ADRs) from a particular medicine. Robust cost-effectiveness results on genetic testing would be useful for clinical practice and policy decision-making on allocating resources effectively. This study aimed to update a systematic review on economic evaluations of pharmacogenetic testing to prevent ADRs and critically appraise the quality of reporting and sources of evidence for model input parameters. Methods We searched studies through Medline via PubMed, Scopus and CRD’s NHS Economic Evaluation up to October 2019. Studies investigating polymorphism-based pharmacogenetic testing, which guided drug therapies to prevent ADRs, using economic evaluation methods were included. Two reviewers independently performed data extraction and assessed the quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines and the quality of data sources using the hierarchy of evidence developed by Cooper et al. Results Fifty-nine economic evaluations of pharmacogenetic testing to avoid drug-induced ADRs were found between 2002 and 2018. Cost-utility and cost-effectiveness analyses were the most common methods of economic evaluation of pharmacogenetic testing. Most studies complied with the CHEERS checklist, except for single study-based economic evaluations which did not report uncertainty analysis (78%). There was a lack of high-quality evidence not only for estimating the clinical effectiveness of pharmacogenetic testing, but also baseline clinical data. About 14% of the studies obtained clinical effectiveness data of testing from a meta-analysis of case-control studies with direct comparison, which was not listed in the hierarchy of evidence used. Conclusions Our review suggested that future single study-based economic evaluations of pharmacogenetic testing should report uncertainty analysis, as this could significantly affect the robustness of economic evaluation results. A specific ranking system for the quality of evidence is needed for the economic evaluation of pharmacogenetic testing of ADRs. Differences in parameters, methods and outcomes across studies, as well as population-level and system-level differences, may lead to the difficulty of comparing cost-effectiveness results across countries.

Background Examine whether the use of different ages has an impact on the valuation of EQ-5D-Y health states for a hypothetical child or adolescent. Methods A survey was administered during regular classes among a convenience sample of university students in the Netherlands. Respondents first valued 6 EQ-5D-Y health states (2 mild, 2 moderate, 2 severe) describing a hypothetical child/adolescent of a certain age on a visual analogue scale (VAS). After 1 h respondents valued the same six health states again but this time the age of the child was different. Age differed between 4, 10 and 16 year old. Results Number of respondents was 311. No significant differences in valuation of the six health states were found between the age of 10 and 16. One moderate health state was valued significantly better for a 4-year old compared to a 10 and a 16 year old. The same applied for one severe health state that was valued higher for a 4-year old compared to a 16-year old. Conclusion Our study shows that, except for one moderate and one severe health state, other EQ-5D-Y health states were not valued significantly different when description of age differed. It is possible that problems in specific health domains are considered more severe for older children/adolescents compared to younger children who might still be dependent on their caregivers. Future research should examine whether our findings are also present in a broader set of EQ-5D-Y health states, with a choice-based method like TTO or DCE, and a more heterogeneous sample.

In addition to more narrow criteria such as safety, effectiveness and cost-effectiveness, vaccines can also be evaluated based on broader criteria such as their economic impact, contribution to disease eradication objectives, caregiver aspects, financial protection offered, equity or social acceptability. We summarize a survey executed in a sample of the population (n = 1000) in Flanders, Belgium, in which we investigated support for using these broader criteria to evaluate vaccines for funding decisions. By means of both favourable and unfavourable framings of a hypothetical vaccine across 40 value dimensions, we find support for the view that people indeed consider a broad range of medical and socio-economic criteria relevant. Several of these are not incorporated in standard evaluation frameworks for vaccines. The different results we find for different framings highlight the importance of developing a consistent a priori value framework for vaccine evaluation, rather than evaluating vaccines on an ad hoc basis. ispartof: Vaccines vol:8 issue:4 ispartof: location:Switzerland status: published

Cost-effectiveness analysis is widely adopted as an analytical framework to evaluate whether health care interventions represent value for money, and its use in dentistry is increasing. Traditionally, in cost-effectiveness analysis, one assumes that the decision maker&rsquo, s maximum willingness to pay (WTP) for health gain is equivalent to his minimum willingness to accept (WTA) monetary compensation for health loss. It has been documented in the literature that losses are weighted higher than equivalent gains, i.e., that WTA exceeds WTP for the same health condition, resulting in a WTA/WTP ratio greater than 1. There is a knowledge gap of published WTA/WTP ratios for dental interventions in the literature. We therefore conducted a (i) systematic review of published WTA-WTP estimates in dentistry (MEDLINE, Web of Science, Cochrane Library, London, UK) and (ii) a patient-level analysis of WTA/WTP ratios of included studies, and (iii) we demonstrate the impact of a WTA-WTP disparity on cost-effectiveness analysis. Out of 55 eligible studies, two studies were included in our review. The WTA/WTP ratio ranged from 2.58 for discontinuing water fluoridation to 5.12 for mandibular implant overdentures, indicating a higher disparity for implant rehabilitations than for dental public health interventions. A WTA-WTP disparity inflates the cost-effectiveness of dental interventions when there is a substantial risk of both lower costs and health outcomes. We therefore recommend that in these cases the results of cost-effectiveness analyses are reported using different WTA/WTP ratios in a sensitivity analysis.

Background Evidence-based decision-making for prioritising health is assisted by health technology assessment (HTA) to integrate data on effectiveness, costs and equity to support transparent decisions. Ghana is moving towards universal health coverage, facilitated mainly by the National Health Insurance Scheme (NHIS) established in 2003. The Government of Ghana is committed to institutionalising HTA for priority-setting. We aimed to identify and describe the sources of accessible data to support HTA in Ghana. Methods We identified and described data sources encompassing six main domains using an existing framework. The domains were epidemiology, clinical efficacy, costs, health service use and consumption, quality of life, and equity. We used existing knowledge, views of stakeholders, and searches of the literature and internet. Results The data sources for each of the six domains vary in extent and quality. Ghana has several large data sources to support HTA (e.g. Demographic Health Surveys) that have rigorous quality assurance processes. Few accessible data sources were available for costs and resource utilisation. The NHIS is a potentially rich source of data on resource use and costs but there are some limits on access. There are some data on equity but data on quality of life are limited. Conclusions A small number of quality data sources are available in Ghana but there are some gaps with respect to HTA based on greater use of local and contextualised information. Although more data are becoming available for monitoring, challenges remain in terms of their usefulness for HTA, and some information may not be available in disaggregated form to enable specific analyses. We support recent initiatives for the routine collection of comprehensive and reliable data that is easily accessible for HTA users. A commitment to HTA will require concerted efforts to leverage existing data sources, for example, from the NHIS, and develop and maintain new data (e.g. local health utility estimates). It will be critical that an overarching strategic and mandatory approach to the collection and use of health information is developed for Ghana in parallel to, and informed by, the development of HTA approaches to support resource allocation decisions. The key to HTA is to use the best available data while being open about its limitations and the impact on uncertainty.

Individual-based models (IBMs) informing public health policy should be calibrated to data and provide estimates of uncertainty. Two main components of model-calibration methods are the parameter-search strategy and the goodness-of-fit (GOF) measure; many options exist for each of these. This review provides an overview of calibration methods used in IBMs modelling infectious disease spread. We identified articles on PubMed employing simulation-based methods to calibrate IBMs informing public health policy in HIV, tuberculosis, and malaria epidemiology published between 1 January 2013 and 31 December 2018. Articles were included if models stored individual-specific information, and calibration involved comparing model output to population-level targets. We extracted information on parameter-search strategies, GOF measures, and model validation. The PubMed search identified 653 candidate articles, of which 84 met the review criteria. Of the included articles, 40 (48%) combined a quantitative GOF measure with an algorithmic parameter-search strategy-either an optimisation algorithm (14/40) or a sampling algorithm (26/40). These 40 articles varied widely in their choices of parameter-search strategies and GOF measures. For the remaining 44 (52%) articles, the parameter-search strategy could either not be identified (32/44) or was described as an informal, non-reproducible method (12/44). Of these 44 articles, the majority (25/44) were unclear about the GOF measure used; of the rest, only five quantitatively evaluated GOF. Only a minority of the included articles, 14 (17%) provided a rationale for their choice of model-calibration method. Model validation was reported in 31 (37%) articles. Reporting on calibration methods is far from optimal in epidemiological modelling studies of HIV, malaria and TB transmission dynamics. The adoption of better documented, algorithmic calibration methods could improve both reproducibility and the quality of inference in model-based epidemiology. There is a need for research comparing the performance of calibration methods to inform decisions about the parameter-search strategies and GOF measures. Author summary Calibration-that is, "fitting" the model to data-is a crucial part of using mathematical models to better forecast and control the population-level spread of infectious diseases. Evidence that the mathematical model is well-calibrated improves confidence that the model provides a realistic picture of the consequences of health policy decisions. To make informed decisions, Policymakers need information about uncertainty: i.e., what is the range of likely outcomes (rather than just a single prediction). Thus, modellers should also strive to provide accurate measurements of uncertainty, both for their model parameters and for their predictions. This systematic review provides an overview of the methods used to calibrate individual-based models (IBMs) of the spread of HIV, malaria, and tuberculosis. We found that less than half of the reviewed articles used reproducible, non-subjective calibration methods. For the remaining articles, the method could either not be identified or was described as an informal, non-reproducible method. Only one-third of the articles obtained estimates of parameter uncertainty. We conclude that the adoption of better-documented, algorithmic calibration methods could improve both reproducibility and the quality of inference in model-based epidemiology. WD was supported by grant 12L5816N from the Research Foundation - Flanders (FWO). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Hazelbag, CM (corresponding author), Stellenbosch Univ, South African DSI NRF Ctr Excellence Epidemiol Mo, Stellenbosch, South Africa. marijnhazelbag@sun.ac.za

Contains fulltext : 225314.pdf (Publisher’s version ) (Open Access) OBJECTIVES: This study analysed the cost-effectiveness of two different attachments for the 2-implant overdenture (2IOD) in edentulous mandibles. MATERIALS AND METHODS: When considering alternative treatments, cost-effectiveness analysis is an important factor for stakeholders (patient, clinician, social security, insurance company, etc.). A general practice population (n = 116) was treated between 2003 and 2013 with a mandibular 2IOD with 2 different ball/stud attachment systems, one spherical (Group D) and one cylindrical (Group L). Patient well-being was assessed with OHIP-14-Total (OHIP-14-T), at intake and annually up to 5 years, to calculate the health effect. Initial and maintenance costs of both treatments were inventoried. The cost-effectiveness was compared. Annual discount rates of 4% and 1.5% were applied to future costs and health outcomes, following Dutch guidelines. Prices were adjusted to the year 2003. To offset the uncertainty in relevant input parameters, a sensitivity analysis was performed using bootstrap analysis. Significance was set at p

Background: Falls are an increasing problem among older people. There are several evidence-based interventions available to prevent falls. However, these are not always well implemented in the primary care setting. General practitioners (GPs) are often the first point of contact for health issues, making them the designated professionals for providing falls prevention. Because GPs are often unaware which patients have a high fall risk and patients themselves do not always know they have a high fall risk, this study aims to evaluate the implementation of a targeted fall risk screening strategy among independently living, frail older people in the primary care setting. Materials and methods: The targeted fall risk screening strategy used in this study consists of tools for screening high fall risk and for identifying the underlying cause(s) of the high fall risk, an accredited training course in falls prevention for professionals, and service provision by certified physio- and exercise therapists who are able to offer evidence-based falls prevention interventions. This targeted fall risk screening strategy will be implemented in the primary care setting and evaluated at the level of the GP practice and at the level of the patient by using the RE-AIM model of Glasgow et al. In a pre-posttest design, data will be collected of the total number of frail older people who are screened, referred and enrolled for fall-preventive care. Furthermore, barriers and facilitators of the implementation of the fall risk screening strategy will be identified by conducting focus groups and interviews with the care providers and frail older patients. Additionally, the influence of the falls prevention interventions on frail older patients will be evaluated by using a pre-posttest design with a 12-month follow-up period during which data are collected regarding patients' stability, mobility, strength, balance, self-efficacy, health status, and daily activities. Study Registration: This study is approved by the Medical Ethics Committee Brabant, the Netherlands (NL61582.028.17/ P1732) and registered at the Netherlands Trial Register, NL7917.

Context Resources for medical education are becoming more constrained, whereas accountability in medical education is increasing. In this constrictive environment, medical schools need to consider and justify their selection procedures in terms of costs and benefits. To date, there have been no studies focusing on this aspect of selection. Objectives We aimed to examine and compare the costs and benefits of two different approaches to admission into medical school: a tailored, multimethod selection process versus a lottery procedure. Our goal was to assess the relative effectiveness of each approach and to compare these in terms of benefits and costs from the perspective of the medical school. Methods The study was conducted at Maastricht University Medical School, at which the selection process and a weighted lottery procedure ran in parallel for 3 years (2011–2013). The costs and benefits of the selection process were compared with those of the lottery procedure over three student cohorts throughout the Bachelor's programme. The extra costs of selection represented the monetary investment of the medical school in conducting the selection procedure; the benefits were derived from the increase in income generated by the prevention of dropout and the reductions in extra costs facilitated by decreases in the repetition of blocks and objective structured clinical examinations. Results The tailor‐made selection procedure cost about €139 000 when extrapolated to a full cohort of students (n = 286). The lottery procedure came with negligible costs for the medical school. However, the average benefits of selection compared with the lottery system added up to almost €207 000. Conclusions This study not only shows that conducting a cost–benefit comparison is feasible in the context of selection for medical school, but also that an ‘expensive’ selection process can be cost‐beneficial in comparison with an ‘inexpensive’ lottery system. We encourage other medical schools to examine the cost‐effectiveness of their own selection processes in relation to student outcomes in order to extend knowledge on this important topic., It's too expensive! Although feasibility is a common concern about selection practice, this study shows through cost‐benefit comparison that ‘expensive’ admissions processes can be cheaper than ‘inexpensive’ lotteries

International audience; Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a key component of the hepatitis B burden worldwide. Despite its efficacy to prevent HBV transmission, infant vaccination is not enough to control HBV MTCT. Additional efforts are urgently needed to evaluate and scale-up preventive strategies especially in endemic countries, which are most affected. This review highlights the efficacy and barriers of the currently validated measures for the prevention of HBV MTCT and proposes alternatives adapted to resource-limited settings to eventually achieve HBV elimination worldwide.