Assessing the value of orphan drugs using conventional cost-effectiveness analysis:Is it fit for purpose?

Conventional cost-effectiveness analysis-i.e., assessing pharmaceuticals through a cost per quality-adjusted life year (QALY) framework-originated from a societal commitment to maximize population health given limited resources. This "extra-welfarist" approach has produced pricing and reimbursement systems that are not well- aligned with the unique considerations of orphan drugs. This framework has been slow to evolve along with our increased understanding of the impact of rare diseases, which in turn has complicated the assessment of orphan drugs meant to treat rare diseases. Herein, we (i) discuss the limitations of conventional cost-effectiveness analysis as applied to assessing access to, as well as the pricing and reimbursement of, orphan drugs, (ii) critically appraise alternative and supplemental approaches, and (iii) offer insights on plausible steps forward

Impact of metabolic comorbidity on the association between body mass index and heatlh-related quality of life: a Scotland-wide cross-sectional study of 5,608 participants

<p/>Background: The prevalence of obesity is rising in Scotland and globally. Overall, obesity is associated with increased morbidity, mortality and reduced health-related quality of life. Studies suggest that "healthy obesity" (obesity without metabolic comorbidity) may not be associated with morbidity or mortality. Its impact on health-related quality of life is unknown. <p/>Methods: We extracted data from the Scottish Health Survey on self-reported health-related quality of life, body mass index (BMI), demographic information and comorbidity. SF-12 responses were converted into an overall health utility score. Linear regression analyses were used to explore the association between BMI and health utility, stratified by the presence or absence of metabolic comorbidity (diabetes, hypertension, hypercholesterolemia or cardiovascular disease), and adjusted for potential confounders (age, sex and deprivation quintile). <p/>Results: Of the 5,608 individuals, 3,744 (66.8%) were either overweight or obese and 921 (16.4%) had metabolic comorbidity. There was an inverted U-shaped relationship whereby health utility was highest among overweight individuals and fell with increasing BMI. There was a significant interaction with metabolic comorbidity (p = 0.007). Individuals with metabolic comorbidty had lower utility scores and a steeper decline in utility with increasing BMI (morbidly obese, adjusted coefficient: -0.064, 95% CI -0.115, -0.012, p = 0.015 for metabolic comorbidity versus -0.042, 95% CI -0.067, -0.018, p = 0.001 for no metabolic comorbidity). <p/>Conclusions: The adverse impact of obesity on health-related quality of life is greater among individuals with metabolic comorbidity. However, increased BMI is associated with reduced health-related quality of life even in the absence of metabolic comorbidity, casting doubt on the notion of "healthy obesity"

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Cost-effectiveness of an exercise program during pregnancy to prevent gestational diabetes: Results of an economic evaluation alongside a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM and the risks associated with GDM lead to increased health care costs and losses in productivity. The objective of this study is to evaluate whether the FitFor2 exercise program during pregnancy is cost-effective from a societal perspective as compared to standard care.</p> <p>Methods</p> <p>A randomised controlled trial (RCT) and simultaneous economic evaluation of the FitFor2 program were conducted. Pregnant women at risk for GDM were randomised to an exercise program to prevent high maternal blood glucose (n = 62) or to standard care (n = 59). The exercise program consisted of two sessions of aerobic and strengthening exercises per week. Clinical outcome measures were maternal fasting blood glucose levels, insulin sensitivity and infant birth weight. Quality of life was measured using the EuroQol 5-D and quality-adjusted life-years (QALYs) were calculated. Resource utilization and sick leave data were collected by questionnaires. Data were analysed according to the intention-to-treat principle. Missing data were imputed using multiple imputations. Bootstrapping techniques estimated the uncertainty surrounding the cost differences and incremental cost-effectiveness ratios.</p> <p>Results</p> <p>There were no statistically significant differences in any outcome measure. During pregnancy, total health care costs and costs of productivity losses were statistically non-significant (mean difference €1308; 95%CI €-229 - €3204). The cost-effectiveness analyses showed that the exercise program was not cost-effective in comparison to the control group for blood glucose levels, insulin sensitivity, infant birth weight or QALYs.</p> <p>Conclusion</p> <p>The twice-weekly exercise program for pregnant women at risk for GDM evaluated in the present study was not cost-effective compared to standard care. Based on these results, implementation of this exercise program for the prevention of GDM cannot be recommended.</p> <p>Trial registration</p> <p>NTR1139</p

Cost-Effectiveness of a Telephone-Delivered Intervention for Physical Activity and Diet

Background: Given escalating rates of chronic disease, broad-reach and cost-effective interventions to increase physical activity and improve dietary intake are needed. The cost-effectiveness of a Telephone Counselling intervention to improve physical activity and diet, targeting adults with established chronic diseases in a low socio-economic area of a major Australian city was examined. Methodology/Principal Findings: A cost-effectiveness modelling study using data collected between February 2005 and November 2007 from a cluster-randomised trial that compared Telephone Counselling with a “Usual Care” (brief intervention) alternative. Economic outcomes were assessed using a state-transition Markov model, which predicted the progress of participants through five health states relating to physical activity and dietary improvement, for ten years after recruitment. The costs and health benefits of Telephone Counselling, Usual Care and an existing practice (Real Control) group were compared. Telephone Counselling compared to Usual Care was not cost-effective ($78,489 per quality adjusted life year gained). However, the Usual Care group did not represent existing practice and is not a useful comparator for decision making. Comparing Telephone Counselling outcomes to existing practice (Real Control), the intervention was found to be cost-effective ($29,375 per quality adjusted life year gained). Usual Care (brief intervention) compared to existing practice (Real Control) was also cost-effective ($12,153 per quality adjusted life year gained). Conclusions/Significance: This modelling study shows that a decision to adopt a Telephone Counselling program over existing practice (Real Control) is likely to be cost-effective. Choosing the ‘Usual Care’ brief intervention over existing practice (Real Control) shows a lower cost per quality adjusted life year, but the lack of supporting evidence for efficacy or sustainability is an important consideration for decision makers. The economics of behavioural approaches to improving health must be made explicit if decision makers are to be convinced that allocating resources toward such programs is worthwhile

Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature

Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be “all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty”. The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios

Optimal Cost-Effectiveness Decisions: The Role of the Cost-Effectiveness Acceptability Curve (CEAC), the Cost-Effectiveness Acceptability Frontier (CEAF), and the Expected Value of Perfection Information (EVPI)

Objective: To demonstrate how the optimal decision and level of uncertainty associated with that decision, can be presented when assessing the cost-effectiveness of multiple options. To explore and explain potentially counterintuitive results that can arise when analyzing multiple options. Methods: A template was created, based on the assumption of multivariate normality, in order to replicate a previous analysis that compared the cost-effectiveness of multiple options. We used this template to explain some of the different shapes that the cost-effectiveness acceptability curve (CEAC), cost-effectiveness acceptability frontier (CEAF), and expected value of perfection information (EVPI) may take, with changing correlation structure and variance between the multiple options. Results: We show that it is possible for 1) an option that is subject to extended dominance to have the highest probability of being cost-effective for some values of the cost-effectiveness threshold; 2) the most cost-effective (optimal) option to never have the highest probability of being cost-effective; and 3) the EVPI to increase when the probability of making the wrong decision decreases. Changing the correlation structure between multiple options did not change the presentation of results on the cost-effectiveness plane. Conclusion: The cost-effectiveness plane has limited use in representing the uncertainty surrounding multiple options as it cannot represent correlation between the options. CEACs can represent decision uncertainty, but should not be used to determine the optimal decision. Instead, the CEAF shows the decision uncertainty surrounding the optimal choice and this can be augmented by the EVPI to show the potential gains to further research

Using and interpreting cost-effectiveness acceptability curves: an example using data from a trial of management strategies for atrial fibrillation

Background: The cost-effectiveness acceptability curve (CEAC) is a method for summarizing the uncertainty in estimates of cost-effectiveness. The CEAC, derived from the joint distribution of costs and effects, illustrates the (Bayesian) probability that the data are consistent with a true cost-effectiveness ratio falling below a specified ceiling ratio. The objective of the paper is to illustrate how to construct and interpret a CEAC. Methods A retrospective cost-effectiveness analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) randomized controlled trial with 4060 patients followed for 3.5 years. The target population was patients with atrial fibrillation who were 65 years of age or had other risk factors for stroke or death similar to those enrolled in AFFIRM. The intervention involved the management of patients with atrial fibrillation with antiarrhythmic drugs (rhythm-control) compared with drugs that control heart rate (rate-control). Measurements of mean survival, mean costs and incremental cost-effectiveness were made. The uncertainty surrounding the estimates of cost-effectiveness was illustrated through a cost-effectiveness acceptability curve. Results The base case point estimate for the difference in effects and costs between rate and rhythm-control is 0.08 years (95% CI: -0.1 years to 0.24 years) and -US$5,077 (95$1,100 to -$11,006). The CEAC shows that the decision uncertainty surrounding the adoption of rate-control strategies is less than 1.7% regardless of the maximum acceptable ceiling ratio. Thus, there is very little uncertainty surrounding the decision to adopt rate-control compared to rhythm-control for patients with atrial fibrillation from a resource point of view. Conclusion The CEAC is straightforward to calculate, construct and interpret. The CEAC is useful to a decision maker faced with the choice of whether or not to adopt a technology because it provides a measure of the decision uncertainty surrounding the choice.Health Care and Epidemiology, Department ofMedicine, Faculty ofNon UBCReviewedFacult

Comparison of mass and targeted screening strategies for cardiovascular risk : simulation of the effectiveness, cost-effectiveness and coverage from a cross sectional survey of 3291 people

Background: Cardiovascular primary prevention should be targeted at those with the highest global risk. However, it is unclear how best to identify such individuals from the general population. The aim of this study was to compare mass and targeted screening strategies in terms of effectiveness, cost effectiveness and coverage. Methods: The Scottish Health Survey provided crosssectional data on 3921 asymptomatic members of the general population aged 40-74 years. We undertook simulation models of five screening strategies: mass screening, targeted screening of deprived communities, targeted screening of family members and combinations of the latter two. Results: To identify one individual at high risk of premature cardiovascular disease using mass screening required 16.0 people to be screened at a cost of £370. Screening deprived communities targeted 17% of the general population but identified 45% of those at high risk, and identified one high-risk individual for every 6.1 people screened at a cost of £141. Screening family members targeted 28% of the general population but identified 61% of those at high risk, and identified one high-risk individual for every 7.4 people screened at a cost of £170. Combining both approaches enabled 84% of high risk individuals to be identified by screening only 41% of the population. Extending targeted to mass screening identified only one additional high-risk person for every 58.8 screened at a cost of £1358. Conclusions: Targeted screening strategies are less costly than mass screening, and can identify up to 84% of high-risk individuals. The additional resources required for mass screening may not be justified