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Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and key funders. These analyses would be of use, as HAT is currently being prioritized as a neglected tropical disease (NTD) to reach elimination by 2020.

Complete reporting assists readers in confirming the methodological rigor and validity of findings and allows replication. The reporting quality of observational functional magnetic resonance imaging (fMRI) studies involving clinical participants is unclear. We sought to determine the quality of reporting in observational fMRI studies involving clinical participants. We searched OVID MEDLINE for fMRI studies in six leading journals between January 2010 and December 2011.Three independent reviewers abstracted data from articles using an 83-item checklist adapted from the guidelines proposed by Poldrack et al. (Neuroimage 2008; 40: 409-14). We calculated the percentage of articles reporting each item of the checklist and the percentage of reported items per article. A random sample of 100 eligible articles was included in the study. Thirty-one items were reported by fewer than 50% of the articles and 13 items were reported by fewer than 20% of the articles. The median percentage of reported items per article was 51% (ranging from 30% to 78%). Although most articles reported statistical methods for within-subject modeling (92%) and for between-subject group modeling (97%), none of the articles reported observed effect sizes for any negative finding (0%). Few articles reported justifications for fixed-effect inferences used for group modeling (3%) and temporal autocorrelations used to account for within-subject variances and correlations (18%). Other under-reported areas included whether and how the task design was optimized for efficiency (22%) and distributions of inter-trial intervals (23%). This study indicates that substantial improvement in the reporting of observational clinical fMRI studies is required. Poldrack et al.'s guidelines provide a means of improving overall reporting quality. Nonetheless, these guidelines are lengthy and may be at odds with strict word limits for publication; creation of a shortened-version of Poldrack's checklist that contains the most relevant items may be useful in this regard.

Background In the absence of head-to-head trials, indirect comparisons of randomized placebo-controlled trials may provide a viable option to assess relative efficacy. The purpose was to estimate the relative efficacy of reduction of fractures in post-menopausal women, and to assess robustness of the results. Methods A systematic literature review of multiple databases identified randomized placebo-controlled trials with nine drugs for post-menopausal women. Odds ratio and 95% credibility intervals for the rates of hip, non-vertebral, vertebral, and wrist fractures for each drug and between drugs were derived using a Bayesian approach. A drug was ranked as the most efficacious if it had the highest posterior odds ratio, or had the highest effect size. Results 30 studies including 59,209 patients reported fracture rates for nine drugs: alendronate (6 studies), denosumab (1 study), etidronate (8 studies), ibandronate (4 studies), raloxifene (1 study), risedronate (7 studies), strontium (2 study), teriparatide (1 study), and zoledronic acid (1 study). The drugs with the highest probability of reducing non-vertebral fractures was etidronate and teriparatide while the drugs with the highest probability of reducing vertebral, hip or wrist fractures were teriparatide, zoledronic acid and denosumab. The drugs with the largest effect size for vertebral fractures were zoledronic acid, teriparatide and denosumab, while the drugs with the highest effect size for non-vertebral, hip or wrist fractures were alendronate or risedronate. Estimates were consistent between Bayesian and classical approaches. Conclusion Teriparatide, zoledronic acid and denosumab have the highest probabilities of being most efficacious for non-vertebral and vertebral fractures, and having the greatest effect sizes. The estimates from indirect comparisons were robust to differences in methodology.

Background Cost-utility analyses are commonly used in economic evaluations of interventions or conditions that have an impact on health-related quality of life. However, evaluating utilities in children presents several challenges since young children may not have the cognitive ability to complete measurement tasks and thus utility values must be estimated by proxy assessors. Another solution is to use utilities derived from an adult population. To better inform the future conduct of cost-utility analyses in paediatric populations, we reviewed the published literature reporting utilities among children and adults across selected conditions common to paediatric and adult populations. Methods An electronic search of Ovid MEDLINE, EMBASE, and the Cochrane Library up to November 2008 was conducted to identify studies presenting utility values derived from the Health Utilities Index (HUI) or EuroQoL-5Dimensions (EQ-5D) questionnaires or using time trade off (TTO) or standard gamble (SG) techniques in children and/or adult populations from randomized controlled trials, comparative or non-comparative observational studies, or cross-sectional studies. The search was targeted to four chronic diseases/conditions common to both children and adults and known to have a negative impact on health-related quality of life (HRQoL). Results After screening 951 citations identified from the literature search, 77 unique studies included in our review evaluated utilities in patients with asthma (n = 25), cancer (n = 23), diabetes mellitus (n = 11), skin diseases (n = 19) or chronic diseases (n = 2), with some studies evaluating multiple conditions. Utility values were estimated using HUI (n = 33), EQ-5D (n = 26), TTO (n = 12), and SG (n = 14), with some studies applying more than one technique to estimate utility values. 21% of studies evaluated utilities in children, of those the majority being in the area of oncology. No utility values for children were reported in skin diseases. Although few studies provided comparative information on utility values between children and adults, results seem to indicate that utilities may be similar in adolescents and young adults with asthma and acne. Differences in results were observed depending on methods and proxies. Conclusions This review highlights the need to conduct future research regarding measurement of utilities in children.

Objectives The goal of this study was to analyze healthrelated quality of life (HRQL) data from a Canadian population with type 2 diabetes in order to estimate the disutility associated with experiencing a diabetes-related complication. Methods The EQ-5D, a standardized instrument for use as a measure of health outcome, was administered to 1,147 patients in Hamilton, Ontario, with type 2 diabetes. After controlling for age, gender, and duration of diabetes, changes in utility values were estimated by regressing the EQ-5D scores onto binary indicators for the presence of an event. The primary method of analysis was Ordinary Least Squares (OLS) and due to concerns over non-Normality, bootstrap standard errors (SE) were calculated. Results The analysis included 1,143 participants. Based on the OLS model, reductions in HRQL were associated with duration of diabetes (-0.0015, SE = 0.0006), experiencing a myocardial infarction (MI) (-0.059, SE = 0.017), amputation (-0.063, SE = 0.059), stroke (-0.046, SE = 0.023), and kidney failure (-0.102, SE = 0.047). Conclusion This study estimated the reductions in HRQL associated with several important complications commonly experienced in patients with diabetes. The greatest impacts on HRQL were associated with kidney failure and MI. The utility values calculated here can be used to assess the outcome of interventions that reduce these diabetes-related complications and will have a useful impact on future economic evaluations of diabetes management strategies in Canada.

Background Patients with a cortical small (≤4 cm) renal mass often are not candidates for or choose not to undergo surgery. The optimal management strategy for such patients is unclear. Methods A decision-analytic Markov model was developed from the perspective of a third party payer to compare the quality-adjusted life expectancy and lifetime costs for 67-year-old patients with a small renal mass undergoing premanagement decision biopsy, immediate percutaneous radiofrequency ablation or percutaneous cryoablation (without premanagement biopsy), or active surveillance with serial imaging and subsequent ablation if needed. Results The dominant strategy (most effective and least costly) was active surveillance with subsequent cryoablation if needed. On a quality-adjusted and discounted basis, immediate cryoablation resulted in a similar life expectancy (3 days fewer) but cost $3,010 more. This result was sensitive to the relative rate of progression to metastatic disease. Strategies that employed radiofrequency ablation had decreased quality-adjusted life expectancies (82–87 days fewer than the dominant strategy) and higher costs ($3,231–$6,398 more). Conclusions Active surveillance with delayed percutaneous cryoablation, if needed, may be a safe and cost-effective alternative to immediate cryoablation. The uncertainty in the relative long-term rate of progression to metastatic disease in patients managed with active surveillance versus immediate cryoablation needs to be weighed against the higher cost of immediate cryoablation. A randomized trial is needed directly to evaluate the nonsurgical management of patients with a small renal mass, and could be limited to the most promising strategies identified in this analysis.

Objective Our aim was to cross-culturally validate Chinese Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in patients with knee osteoarthritis (OA) scheduled for total knee replacement in Singapore. Methods Chinese WOMAC was translated from the original English version following standard guidelines. Patients were asked to complete a questionnaire containing the WOMAC (twice within 6 days), the Short Form 36 (SF-36), and the EuroQoL EQ-5D. Reliability was assessed using Cronbach's alpha and intraclass correlation coefficients (ICC), dimensionality using item-to-domain correlations and factor analyses. Convergent and discriminant construct validity was assessed using six each a priori hypotheses.Results Chinese WOMAC was well accepted by the patients in the pilot test. The Chinese and English versions were therefore administered to a consecutive sample of 131 Chinese-and 127 English-speaking subjects, respectively, with knee OA. Cronbach's alpha exceeded 0.7 for all domains except for Chinese pain domain, whereas the ICC exceeded 0.7 for all domains. Hypothesized item-todomain correlations were observed for all items except for four items in Chinese physical function domain. The factor analyses yielded seven and five factors with eigenvalues of more than 1.0 in the Chinese and English versions, respectively. A total of 10/12 a priori construct validity hypotheses were satisfied for the Chinese version. Weak correlations between WOMAC pain and SF-36 bodily pain and moderate correlation between WOMAC pain and EQ-5D anxiety/depression were observed. Conclusions Chinese WOMAC was well accepted and demonstrated acceptable psychometric properties in Singaporean patients with severe knee OA.

Health technology assessments (HTA) generally, and economic evaluations (EE) more specifically, have become an integral part of health care decision making around the world. However, these assessments are time consuming and expensive to conduct. Evaluation resources are scarce and therefore priorities need to be set for these assessments and the ability to use information from one country or region in another (geographic transferability) is an increasingly important consideration. To review the existing approaches, systems, and tools for assessing the geographic transferability potential or guiding the conduct of transferring HTAs and EEs. A systematic literature review was conducted of several databases, supplemented with web searching, hand searching of journals, and bibliographic searching of identified articles. Systems, tools, checklists, and flow charts to assess, evaluate, or guide the conduct of transferability of HTAs and EEs were identified. Of 282 references identified, 27 articles were reviewed in full text and of these, seven proposed unique systems, tools, checklists, or flow charts specifically for geographic transferability. All of the seven articles identified a checklist of transferability factors to consider, and most articles identified a subset of 'critical' factors for assessing transferability potential. Most of these critical factors related to study quality, transparency of methods, the level of reporting of methods and results, and the applicability of the treatment comparators to the target country. Some authors proposed a sequenced flow chart type approach, while others proposed an assessment of critical criteria first, followed by an assessment of other noncritical factors. Finally some authors proposed a quantitative score or index to measure transferability potential. Despite a number of publications on the topic, the proposed approaches and the factors used for assessing geographic transferability potential have varied substantially across the papers reviewed. Most promising is the identification of an extensive checklist of critical and noncritical factors in determining transferability potential, which may form the basis for consensus of a future tool. Due to the complexities of identifying appropriate weights for each of the noncritical factors, it is still uncertain whether the assessment and calculation of an overall transferability score or index will be practical or useful for transferability considerations in the future.

In recent years, the quest for more comprehensiveness, structure and transparency in reimbursement decision-making in healthcare has prompted the research into alternative decision-making frameworks. In this environment, multi-criteria decision analysis (MCDA) is arising as a valuable tool to support healthcare decision-making. In this paper, we present the main MCDA decision support methods (elementary methods, value-based measurement models, goal programming models and outranking models) using a case study approach. For each family of methods, an example of how an MCDA model would operate in a real decision-making context is presented from a critical perspective, highlighting the parameters setting, the selection of the appropriate evaluation model as well as the role of sensitivity and robustness analyses. This study aims to provide a step-by-step guide on how to use MCDA methods for reimbursement decision-making in healthcare.

Objectives To quantify the improvement in health outcomes in patients after total knee replacement (TKR). Methods This was a two-year non-randomized prospective observational study in knee osteoarthritis (OA) patients undergone TKR. Patients were interviewed one week before, six months after, and two years after surgery using a standardized questionnaire including the SF-36, the Oxford Knee Score (OKS), and the Knee Society Clinical Rating Scale (KSS). A generalized estimating equation (GEE) model was used to estimate the magnitudes of the changes with and without the adjustment of age, ethnicity, BMI, and years with OA. Results A total of 298 (at baseline), 176 (at six-months), and 111 (at two-years) eligible patients were included in the analyses. All the scores changed significantly over time, with the exception of SF-36 social functioning, vitality, and mental health. With the adjustment of covariates, the magnitude of changes in these scores was similar to those without the adjustment. Conclusions Both general and knee-specific physical functioning had been significantly improved after TKR, while other health domains have not been substantially improved after the surgery.