Showing papers in "PharmacoEconomics in 2010"
TL;DR: Matching adjustment ensured that this indirect comparison was not biased by differences in mean baseline characteristics across trials, supporting the conclusion that adalimumab was associated with significantly greater symptom reduction than etanercept for the treatment of moderate to severe psoriasis.
Abstract: The absence of head-to-head trials is a common challenge in comparative effectiveness research and health technology assessment. Indirect cross-trial treatment comparisons are possible, but can be biased by cross-trial differences in patient characteristics. Using only published aggregate data, adjustment for such biases may be impossible. Although individual patient data (IPD) would permit adjustment, they are rarely available for all trials. However, many researchers have the opportunity to access IPD for trials of one treatment, a new drug for example, but only aggregate data for trials of comparator treatments. We propose a method that leverages all available data in this setting by adjusting average patient characteristics in trials with IPD to match those reported for trials without IPD. Treatment outcomes, including continuous, categorical and censored time-to-event outcomes, can then be compared across balanced trial populations. The proposed method is illustrated by a comparison of adalimumab and etanercept for the treatment of psoriasis. IPD from trials of adalimumab versus placebo (n = 1025) were re-weighted to match the average baseline characteristics reported for a trial of etanercept versus placebo (n = 330). Reweighting was based on the estimated propensity of enrolment in the adalimumab versus etanercept trials. Before matching, patients in the adalimumab trials had lower mean age, greater prevalence of psoriatic arthritis, less prior use of systemic treatment or phototherapy, and a smaller mean percentage of body surface area affected than patients in the etanercept trial. After matching, these and all other available baseline characteristics were well balanced across trials. Symptom improvements of ≥75% and ≥90% (as measured by the Psoriasis Area and Severity Index [PASI] score at week 12) were experienced by an additional 17.2% and 14.8% of adalimumab-treated patients compared with the matched etanercept-treated patients (respectively, both p < 0.001). Mean percentage PASI score improvements frombaseline were also greater for adalimumab than for etanercept at weeks 4, 8 and 12 (all p < 0.05). Matching adjustment ensured that this indirect comparison was not biased by differences in mean baseline characteristics across trials, supporting the conclusion that adalimumab was associated with significantly greater symptom reduction than etanercept for the treatment of moderate to severe psoriasis.
233 citations
TL;DR: There was a significant increase in costs associated with an increase in disease severity as measured by the Kurtzke Expanded Disability Status Scale (EDSS) score and the increase in magnitude was coupled with changes in the distribution of costs.
Abstract: Multiple sclerosis (MS) is a disease of the CNS, typically striking adults during the primary productive time of their life. The symptoms of MS can restrict the individual’s physical activity and income-earning ability, resulting in a major financial burden on the patient, family, health system and society. This systematic literature review was conducted to document the economic burden of MS. Employing pre-defined search terms and inclusion/exclusion criteria, systematic searches were conducted in MEDLINE, EMBASE, PsycINFO, the Health Economic Evaluations Database (HEED), the NHS Economic Evaluation Database (EED) and the UK National Institute for Health and Clinical Excellence (NICE) website as well as conference abstracts. We identified 29 cost-of-illness studies that met the a priori inclusion criteria. The cost categories responsible for the majority of costs associated with MS varied across countries. There was a significant increase in costs associated with an increase in disease severity as measured by the Kurtzke Expanded Disability Status Scale (EDSS) score. The increase in magnitude was coupled with changes in the distribution of costs; although direct medical costs were important contributors in earlier stages of disease, they were outweighed by indirect costs in later stages, mainly due to relapses and productivity losses. Considering the increased costs associated with relapse occurrence and increasing disease severity, pharmaceutical or non-pharmaceutical interventions aimed at delaying the progression of disease may help to reduce the economic burden of MS.
196 citations
TL;DR: Although study designs differed across the articles, SRQs appeared to report a higher rate of medication adherence than monitoring devices, and could be considered for measuring patient-reported adherence prospectively.
Abstract: The primary objective of this review was to identify and examine the literature on the association between medication adherence self-reported questionnaires (SRQs) and medication monitoring devices. The primary literature search was performed for 1980–2009 using PubMed, PubMed In Process and Non-Indexed, Ovid MEDLINE, Ovid MEDLINE In-Process, PsycINFO (EBSCO), CINAHL (EBSCO), Ovid HealthStar, EMBASE (Elsevier) and Cochrane Databases and using the following search terms: ‘patient compliance’, ‘medication adherence’, ‘treatment compliance’, ‘drug monitoring’, ‘drug therapy’, ‘electronic’, ‘digital’, ‘computer’, ‘monitor’, ‘monitoring’, ‘drug’, ‘drugs’, ‘pharmaceutical preparations’, ‘compliance’ and ‘medications’. We identified studies that included SRQs and electronic monitoring devices to measure adherence and focused on the SRQs that were found to be moderately to highly correlated with the monitoring devices.
191 citations
TL;DR: This is the first attempt at a comprehensive analysis of methods that have been used to address uncertainty concerning a new drug or other technology and reveals that, although various approaches have been experimented with, many of them have not achieved the ostensible goal of the approach.
Abstract: As tensions between payers, responsible for ensuring prudent and principled use of scarce resources, and both providers and patients, who legitimately want access to technologies from which they could benefit, continue to mount, interest in approaches to managing the uncertainty surrounding the introduction of new health technologies has heightened.
136 citations
TL;DR: The cost burden of NV fracture patients to payers is substantial, and although hip fracture patients were more costly per patient in both Medicare and privately insured samples, NVNH fracture patients still had substantial incremental costs.
Abstract: Background: Osteoporosis is a condition marked by low bone mineral density and the deterioration of bone tissue. One of the main clinical and economic consequences of osteoporosis is skeletal fractures. Objective: To assess the healthcare and work loss costs of US patients with non-vertebral (NV) osteoporotic fractures. Methods: Privately insured (aged 18–64 years) and Medicare (aged ≥65 years) patients with osteoporosis (ICD-9-CM code: 733.0x) were identified during 1999–2006 using two claims databases. Patients with an NV fracture (femur, pelvis, lower leg, upper arm, forearm, rib or hip) were matched randomly on age, sex, employment status and geographic region to controls with osteoporosis and no fractures. Patient characteristics and annual healthcare costs were assessed over the year following the index fracture for privately insured (n = 4764) and Medicare (n = 48 742) beneficiaries (Medicare drug costs were estimated using multivariable models). Indirect (i.e. work loss) costs were calculated for a subset of privately insured, employed patients with available disability data (n = 1148). All costs were reported in $US, year 2006 values. Results: In Medicare, mean incremental healthcare costs per NV fracture patient were $US13 387 ($US22 466 vs $US9079; p < 0.05). The most expensive patients had index fractures of the hip, multiple sites and femur (incremental costs of $US25 519, $US20 137 and $US19 403, respectively). Patients with NV non-hip (NVNH) fractures had incremental healthcare costs of $US7868 per patient ($US16 704 vs $US8836; p < 0.05). Aggregate annual incremental healthcare costs of NVNH patients in the Medicare research sample (n = 35 933) were $US282.7 million compared with $US204.1 million for hip fracture patients (n = 7997). Among the privately insured, mean incremental healthcare costs per NV fracture patient were $US5961 ($US11 636 vs $US5675; p < 0.05). The most expensive patients had index fractures of the hip, multiple sites and pelvis (incremental costs of $US13 801, $US9642 and $US8164, respectively). Annual incremental healthcare costs per NVNH patient were $US5381 ($US11 090 vs $US5709; p < 0.05). Aggregate annual incremental healthcare costs of NVNH patients in the privately insured sample (n = 4478) were $US24.1 million compared with $US3.5 million for hip fracture patients (n = 255). Mean incremental work loss costs per NV fracture employee were $US1956 ($US4349 vs $US2393; p < 0.05). Among patients with available disability data, work loss accounted for 29.5% of total costs per NV fracture employee. Conclusion: The cost burden of NV fracture patients to payers is substantial. Although hip fracture patients were more costly per patient in both Medicare and privately insured samples, NVNH fracture patients still had substantial incremental costs. Because NVNH patients accounted for a larger proportion of the fracture population, they were associated with greater aggregate incremental healthcare costs than hip fracture patients.
120 citations
TL;DR: VOI methods applying the central limit theorem (CLT) simplifies analysis to enable easy estimation of EVSI and optimal overall research design, and has been shown to outperform bootstrapping, particularly with small samples.
Abstract: Value of information (VOI) methods have been proposed as a systematic approach to inform optimal research design and prioritization. Four related questions arise that VOI methods could address. (i) Is further research for a health technology assessment (HTA) potentially worthwhile? (ii) Is the cost of a given research design less than its expected value? (iii) What is the optimal research design for an HTA? (iv) How can research funding be best prioritized across alternative HTAs? Following Occam's razor, we consider the usefulness of VOI methods in informing questions 1-4 relative to their simplicity of use. Expected value of perfect information (EVPI) with current information, while simple to calculate, is shown to provide neither a necessary nor a sufficient condition to address question 1, given that what EVPI needs to exceed varies with the cost of research design, which can vary from very large down to negligible. Hence, for any given HTA, EVPI does not discriminate, as it can be large and further research not worthwhile or small and further research worthwhile. In contrast, each of questions 1-4 are shown to be fully addressed (necessary and sufficient) where VOI methods are applied to maximize expected value of sample information (EVSI) minus expected costs across designs. In comparing complexity in use of VOI methods, applying the central limit theorem (CLT) simplifies analysis to enable easy estimation of EVSI and optimal overall research design, and has been shown to outperform bootstrapping, particularly with small samples. Consequently, VOI methods applying the CLT to inform optimal overall research design satisfy Occam's razor in both improving decision making and reducing complexity. Furthermore, they enable consideration of relevant decision contexts, including option value and opportunity cost of delay, time, imperfect implementation and optimal design across jurisdictions. More complex VOI methods such as bootstrapping of the expected value of partial EVPI may have potential value in refining overall research design. However, Occam's razor must be seriously considered in application of these VOI methods, given their increased complexity and current limitations in informing decision making, with restriction to EVPI rather than EVSI and not allowing for important decision-making contexts. Initial use of CLT methods to focus these more complex partial VOI methods towards where they may be useful in refining optimal overall trial design is suggested. Integrating CLT methods with such partial VOI methods to allow estimation of partial EVSI is suggested in future research to add value to the current VOI toolkit.
115 citations
TL;DR: This article examines performance-based risk-sharing agreements for pharmaceuticals from a theoretical economic perspective and concludes that a value of information/real option framework is likely to be the most helpful approach for understanding the costs and benefits of risk sharing.
Abstract: This article examines performance-based risk-sharing agreements for pharmaceuticals from a theoretical economic perspective. We position these agreements as a form of coverage with evidence development. New performance-based risk sharing could produce a more efficient market equilibrium, achieved by adjustment of the price post-launch to reflect outcomes combined with a new approach to the post-launch costs of evidence collection. For this to happen, the party best able to manage or to bear specific risks must do so. Willingness to bear risk will depend not only on ability to manage it, but on the degree of risk aversion. We identify three related frameworks that provide relevant insights: value of information, real option theory and money-back guarantees. We identify four categories of risk sharing: budget impact, price discounting, outcomes uncertainty and subgroup uncertainty. We conclude that a value of information/real option framework is likely to be the most helpful approach for understanding the costs and benefits of risk sharing. There are a number of factors that are likely to be crucial in determining if performance-based or risk-sharing agreements are efficient and likely to become more important in the future: (i) the cost and practicality of post-launch evidence collection relative to pre-launch; (ii) the feasibility of coverage with evidence development without a pre-agreed contract as to how the evidence will be used to adjust price, revenues or use, in which uncertainty around the pay-off to additional research will reduce the incentive for the manufacturer to collect the information; (iii) the difficulty of writing and policing risk-sharing agreements; (iv) the degree of risk aversion (and therefore opportunity to trade) on the part of payers and manufacturers; and (v) the extent of transferability of data from one country setting to another to support coverage with evidence development in a risk-sharing framework. There is no doubt that--in principle--risk sharing can provide manufacturers and payers additional real options that increase overall efficiency. Given the lack of empirical evidence on the success of schemes already agreed and on the issues we set out above, it is too early to tell if the recent surge of interest in these arrangements is likely to be a trend or only a fad.
113 citations
TL;DR: The available evidence indicates that price-cap regulation leads to a levelling off of generic prices at a higher level than would occur in the absence of this regulation, and the entry of new generic competitors is useful for lowering the real transaction price of purchases made by pharmacies.
Abstract: Although economic theory indicates that it should not be necessary to intervene in the generic drug market through price regulation, most EU countries intervene in this market, both by regulating the maximum sale price of generics (price cap) and by setting the maximum reimbursement rate, especially by means of reference pricing systems. We analyse current knowledge of the impact of direct price-cap regulation of generic drugs and the implementation of systems regulating the reimbursement rate, particularly through reference pricing and similar tools, on dynamic price competition between generic competitors in Europe. A literature search was carried out in the EconLit and PubMed databases, and on Google Scholar. The search included papers published in English or Spanish between January 2000 and July 2009. Inclusion criteria included that studies had to present empirical results of a quantitative nature for EU countries of the impact of price capping and/or regulation of the reimbursement rate (reference pricing or similar systems) on price dynamics, corresponding to pharmacy sales, in the generic drug market. The available evidence indicates that price-cap regulation leads to a levelling off of generic prices at a higher level than would occur in the absence of this regulation. Reference pricing systems cause an obvious and almost compulsory reduction in the consumer price of all pharmaceuticals subject to this system, to a varying degree in different countries and periods, the reduction being greater for originator-branded drugs than for generics. In several countries with a reference pricing system, it was observed that generics with a consumer price lower than the reference price do not undergo price reductions until the reference price is reduced, even when there are other lower-priced generics on the market (absence of price competition below the reference price). Beyond the price reduction forced by the price-cap and/or reference pricing regulation itself, the entry of new generic competitors is useful for lowering the real transaction price of purchases made by pharmacies (dynamic price competition at ex-factory level), although this effect is weaker or non-significant for official ex-factory prices and consumer prices in some countries. When maximum reimbursement systems such as reference pricing or similar types are applied, pharmacies are seen to receive large discounts on the price they pay for the pharmaceuticals, although these discounts are not transferred to the consumer price. The percentage discount offered to pharmacies in a country that uses a price-cap system combined with reference pricing is positively and significantly related to the number of generic competitors in the market for the pharmaceutical (dynamic price competition at ex-factory level).
112 citations
TL;DR: The simulation results suggest that donepezil leads to health benefits and cost savings when used to treat mild to moderately severe Alzheimer’s disease in the UK, and indicate that both benefits and savings may be greatest when treatment is started while patients are still in the mild stages of Alzheimer's disease.
Abstract: Background: Recommendations in the UK suggest restricting treatment of Alzheimer’s disease with cholinesterase inhibitors, on cost-effectiveness grounds, to patients with moderate cognitive decline. As the economic analyses that informed these recommendations have been the subject of debate, we sought to address the potential limitations of existing models and produce estimates of donepezil treatment cost effectiveness in the UK using the most recent available data and simulation techniques. Methods: A discrete-event simulation was developed that predicts progression of Alzheimer’s disease through correlated changes in cognition, behavioural disturbance and function. Patient-level data from seven randomized, placebo-controlled donepezil trials and a 7-year follow-up registry provided the basis for modeling longitudinal outcomes. Individuals in the simulation were assigned unique demographic and clinical characteristics and then followed for 10 years, with severity of disease tracked on continuous scales. Patient mix and costs were developed from UK-specific literature. Analyses were run for severity subgroups to evaluate outcomes for sub-populations with disease of mild versus moderate severity from both a healthcare payer and societal perspective. All costs are reported in £, year 2007 values, and all outcomes are discounted at 3.5% per annum. Results: Over 10 years, treatment of all patients with mild to moderate disease reduces overall direct medical costs by an average of over £2300 per patient. When unpaid caregiver time is also taken into consideration, savings increase to over £4700 per patient. Compared with untreated patients, patients receiving donepezil experience a discounted gain in QALYs averaging 0.11, with their caregivers gaining, on average, 0.01 QALYs. For the subset of patients starting treatment with more severe disease, savings are more modest, averaging about £1600 and £3750 from healthcare and societal perspectives, respectively. In probabilistic sensitivity analyses, donepezil dominated no treatment between 57% and 62% of replications when only medical costs were considered, and between 74% and 79% of replications when indirect costs were included, with results more favourable for treatment initiation in the mild versus moderate severity stages of the disease. Conclusions: Although the simulation results are not definitive, they suggest that donepezil leads to health benefits and cost savings when used to treat mild to moderately severe Alzheimer’s disease in the UK. They also indicate that both benefits and savings may be greatest when treatment is started while patients are still in the mild stages of Alzheimer’s disease.
104 citations
TL;DR: Despite a recent increase in the number of economic evaluations of pharmacogenetic applications, further studies examining the clinical validity and utility of these biomarkers are needed to support cost-effectiveness assessments.
Abstract: The use of pharmacogenetic testing in clinical practice is limited thus far. A potential barrier to the widespread implementation of pharmacogenetic testing is the lack of evidence on whether testing provides good value for money. The objective of this review was to provide a systematic and critical review of economic evaluations of pharmacogenetic testing. A literature search using publically available databases was performed for articles published up to October 2009. To be included, studies had to meet the definition of being a pharmacogenomic study (defined as use of information on human genetic variation to target drug therapy) and an economic evaluation (defined as an evaluation of both costs and clinical outcomes). Articles that met these criteria were subsequently reviewed and graded using the Quality of Health Economic Studies (QHES) instrument. Lastly, the evidence for biomarker validity and utility were qualitatively assessed using expert opinion. A total of 34 articles were identified using our defined criteria. The most common disease category was thromboembolic-related diseases (26%), while the most common biomarkers were thiopurine methyltransferase and cytochrome P450 2C9 (18% each). Almost all studies were published after 2004 (91%). Two types of studies were identified: cost-effectiveness studies and cost-utility studies, with roughly half of the overall studies being cost-utility studies (53%) and a majority of these published within the last 3 years. The average quality score was 77 (range 29-99). Of the biomarkers reviewed, it was estimated that most had demonstrated clinical validity, but only two had demonstrated clinical utility. Despite a recent increase in the number of economic evaluations of pharmacogenetic applications, further studies examining the clinical validity and utility of these biomarkers are needed to support cost-effectiveness assessments.
101 citations
TL;DR: A policy model based on initial clinical studies to date suggests that warfarin pharmacogenomic testing may provide a small clinical benefit with significant uncertainty in economic value.
Abstract: Background: In 2007, the US FDA added information about pharmacogenomics to the warfarin label based on the influence of the CYP2C9 and VKORC1 genes on anticoagulation-related outcomes. Payers will be facing increasing demand for coverage decisions regarding this technology, but the potential clinical and economic impacts of testing are not clear. Objective: To develop a policy model to evaluate the potential outcomes of warfarin pharmacogenomic testing based on the most recently available data. Methods: A decision-analytic Markov model was developed to assess the addition of genetic testing to anticoagulation clinic standard care for a hypothetical cohort of warfarin patients. The model was based on anticoagulation status (international normalized ratio), a common outcome measure in clinical trials that captures both the benefits and risks of warfarin therapy. Initial estimates of testing effects were derived from a recently completed randomized controlled trial (n = 200). Healthcare cost ($US, year 2007 values) and health-state utility data were obtained from the literature. The perspective was that of a US third-party payer. Probabilistic and one-way sensitivity analyses were performed to explore the range of plausible results. Results: The policy model included thromboembolic events (TEs) and bleeding events and was populated by data from the COUMAGEN trial. The rate of bleeding calculated for standard care approximated bleeding rates found in an independent cohort of warfarin patients. According to our model, pharmacogenomic testing provided an absolute reduction in the incidence of bleeds of 0.17%, but an absolute increase in the incidence of TEs of 0.03%. The improvement in QALYs was small, 0.003, with an increase in total cost of $US162 (year 2007 values). The incremental cost-effectiveness ratio (ICER) ranged from testing dominating to standard care dominating, and the ICER was <$US50 000 per QALY in 46% of simulations. Results were most sensitive to the cost of genotyping and the effect of genotyping. Conclusion: Our model, based on initial clinical studies to date, suggests that warfarin pharmacogenomic testing may provide a small clinical benefit with significant uncertainty in economic value. Given the uncertainty in the analysis, further updates will be important as additional clinical data become available.
TL;DR: This work proposes a framework for evaluating current schemes and informing the design of future schemes, and examines the value of the framework using the UK Multiple Sclerosis Risk-Sharing Scheme as a case study.
Abstract: There is an inevitable tension between robust reimbursement processes and providing speedy access to new and novel technologies, given uncertainties about key pieces of evidence and subsequent concerns regarding their overall efficiency. The public perception of these treatments as 'breakthrough', combined with substantial clinical pressure, has led to healthcare payers looking for schemes that allow the new technology to be made available to (some) patients, while (at least partially) protecting the principles of their reimbursement decision-making processes. Current literature on these schemes is almost completely descriptive and provides little help in planning future schemes. We propose a framework for evaluating current schemes and informing the design of future schemes. We examine the value of the framework using the UK Multiple Sclerosis Risk-Sharing Scheme as a case study.
TL;DR: Rapid PCR testing for MRSA appears to have the potential to reduce mortality rates while being less costly than empiric therapy in the EU and US, across a wide range of MRSA prevalence rates and PCR test costs.
Abstract: Background: Patients hospitalized with Staphylococcus aureus bacteraemia have an unacceptably high mortality rate Literature available to date has shown that timely selection of the most appropriate antibacterial may reduce mortality One tool that may help with this selection is a polymerase chain reaction (PCR) assay that distinguishes methicillin (meticillin)-resistant S aureus (MRSA) from methicillin-susceptible S aureus (MSSA) in less than 1 hour To date, no information is available evaluating the impact of this PCR technique on clinical or economic outcomes Objective: To evaluate the effect of a rapid PCR assay on mortality and economics compared with traditional empiric therapy, using a literaturederived model Methods: A literature search for peer-reviewed European (EU) and US publications regarding treatment regimens, outcomes and costs was conducted Information detailing the rates of infection, as well as the specificity and sensitivity of a rapid PCR assay (Xpert MRSA/SA Blood Culture PCR®) were obtained from the peer-reviewed literature Sensitivity analysis varied the prevalence rate of MRSA from 5% to 80%, while threshold analysis was applied to the cost of the PCR test Hospital and testing resource consumption were valued with direct medical costs, adjusted to year 2009 values Adjusted life-years were determined using US and WHO life tables The cost-effectiveness ratio was defined as the cost per life-year saved Incremental cost-effectiveness ratios (ICERs) were calculated to determine the additional cost necessary to produce additional effectiveness All analyses were performed using TreeAge Software (2008) Results: The mean mortality rates were 23% for patients receiving empiric vancomycin subsequently switched to semi-synthetic penicillin (SSP) for MSSA, 36% for patients receiving empiric vancomycin treatment for MRSA, 59% for patients receiving empiric SSP subsequently switched to vancomycin for MRSA and 12% for patients receiving empiric SSP for MSSA Furthermore, with an MRSA prevalence of 30%, the numbers of patients needed to test in order to save one life were 14 and 16 compared with empiric vancomycin and SSP, respectively The absolute mortality difference for MRSA prevalence rates of 80% and 5% favoured the PCR testing group at 2% and 10%, respectively, compared with empiric vancomycin and 18% and 1%, respectively, compared with empiric SSP In the EU, the cost-effectiveness ratios for empiric vancomycin- and SSP-treated patients were h695 and h687 per life-year saved, respectively, compared with h636 per life-year saved for rapid PCR testing In the US, the cost-effectiveness ratio was $US898 per life-year saved for empiric vancomycin and $US820 per life-year saved for rapid PCR testing ICERs demonstrated dominance of the PCR test in all instances Threshold analysis revealed that PCR testing would be less costly overall, even at greatly inflated assay prices Conclusion: Rapid PCR testing for MRSA appears to have the potential to reduce mortality rates while being less costly than empiric therapy in the EU and US, across a wide range of MRSA prevalence rates and PCR test costs
TL;DR: In order to properly care for patients presenting with sleep-related morbidity, and to reduce the consequential economic burden, accurate screening efforts and efficacious/cost-effective treatments need to be developed and employed.
Abstract: Sleep disorders such as insomnia, obstructive sleep apnoea (OSA), excessive daytime sleepiness (EDS) and fatigue, sleep deprivation and restless legs syndrome (RLS) are increasingly seen in clinical practice. Sleep is considered vital for preserving daytime cognitive function and physiological well-being. Sleep insufficiency may have deleterious effects on work-life balance, overall health and safety. The consequential economic burden at both the individual and societal levels is significant. Moreover, sleep disorders are commonly associated with other major medical problems such as chronic pain, cardiovascular disease, mental illness, dementias, gastrointestinal disorders and diabetes mellitus. Thus, in order to properly care for patients presenting with sleep-related morbidity, and to reduce the consequential economic burden, accurate screening efforts and efficacious/cost-effective treatments need to be developed and employed.
TL;DR: Recommendations are offered on the conduct of 21st century QALY valuation exercises that propose to use any tasks that rely on discrete choices, including the estimation of discount factors, proper modelling of the variance scale factor and the estimations of individual-level utility functions.
Abstract: There is increasing interest in using ranking tasks, discrete choice experiments and best-worst scaling studies to estimate QALY values for use in cost-utility analysis. The research frontier in choice modelling is moving rapidly, with a number of issues being explored across several disciplines. These issues include the estimation of discount factors, proper modelling of the variance scale factor and the estimation of individual-level utility functions. Some of these issues are particularly acute when discrete choice tasks are used to facilitate extra-welfarist analyses that rely on population-based values. There are also potential problems in implementing such tasks that have received little interest in the non-health discrete choice literature because they are specific to the QALY framework. This article details these issues and offers recommendations on the conduct of 21st century QALY valuation exercises that propose to use any tasks that rely on discrete choices.
TL;DR: The simulated treatment comparison (STC) approach to incorporating ‘missing arms’ into an existing trial yields a simulated head-to-head trial and can address many of the differences among source trials.
Abstract: Establishing efficacy relative to placebo is no longer sufficient for payers to agree to cover new interventions. Evidence from comparisons of competing interventions is increasingly important, although head-to-head studies are seldom available to inform decisions. In this article, we describe the simulated treatment comparison (STC) approach to incorporating 'missing arms' into an existing trial. This approach yields a simulated head-to-head trial and can address many of the differences among source trials. It provides inputs for economic models and can inform decision makers until actual trial data are available. A simulation is constructed to replicate an index trial, including enrolment, randomization and follow-up of patients. The simulation is driven by predictive equations derived from the index trial. Separate data for the comparators are used to calibrate the index equations to reflect the alternative interventions. The simulation is used to add the missing arms to the index trial and estimate the results that would have been obtained in a head-to-head trial. The STC can also be used to estimate results in various settings and populations and to explore variations in the trial design. An STC offers a way to derive comparative effectiveness in the absence of direct trial evidence and a platform to test design features that may help in planning future head-to-head studies.
TL;DR: It is concluded that while a threshold may be needed to interpret the results of a cost-effectiveness analysis, that threshold must vary across payers, populations and even procedures.
Abstract: The application of cost-effectiveness analysis in healthcare has become commonplace in the US, but the validity of this approach is in jeopardy unless the proverbial $US50 000 per QALY benchmark for determining value for money is updated for the 21st century. While the initial aim of this article was to review the arguments for abandoning the $US50 000 threshold, it quickly turned to questioning whether we should maintain a fixed threshold at all. Our consideration of the relevance of thresholds was framed by two important historical considerations. First, cost-effectiveness analysis was developed for a resource allocation exercise where a threshold would be determined endogenously by maximizing a fixed budget across all possible interventions and not for piecemeal evaluation where a threshold needs to be set exogenously. Second, the foundations of the $US50 000 threshold are highly dubious, so it would be unacceptable merely to adjust for inflation or current clinical practice. Upon consideration of both sides of the argument, we conclude that the arguments for abandoning the concept for maintaining a fixed threshold outweigh those for keeping one. Furthermore, we document a variety of reasons why a threshold needs to vary in the US, including variations across payer, over time, in the true budget impact of interventions and in the measurement of the effectiveness of interventions. We conclude that while a threshold may be needed to interpret the results of a cost-effectiveness analysis, that threshold must vary across payers, populations and even procedures.
TL;DR: The excess direct costs in patients with epilepsy are underestimated when only epilepsy-related costs are considered, and the indirect costs for a subset of employees from an employer perspective are underestimated.
Abstract: Background: The direct cost burden of epilepsy in the US from a third-party payer perspective has not been evaluated. Furthermore, no study has quantified the indirect (work-loss) cost burden of epilepsy from an employer perspective in the US. Objective: To assess the annual direct costs for privately insured US patients diagnosed with epilepsy, and indirect costs for a subset of employees from an employer perspective. Methods: A retrospective analysis of a claims database for the privately insured, including employee disability claims from 1999 through 2005 and comprising 17 US companies, was conducted. A total of 4323 patients aged 16–64 years (including 1886 employees) with at least one epilepsy diagnosis (International Classification of Diseases, 9th edition, Clinical Modification [ICD-9-CM] code 345.x) over the period 19992004 were included. The control group was a demographically matched cohort of randomly chosen beneficiaries without an epilepsy diagnosis. All had continuous health coverage during 2004 (baseline) and 2005 (study period). Main outcome measures included annual direct (medical and pharmaceutical) costs and, for employees, indirect (disability and medically related absenteeism) and total costs for the study period. Wilcoxon rank-sum tests were used for univariate comparisons of annual direct costs, indirect costs (costs for the subset of employees with these data), and total (direct and indirect) costs during the study period. Two-part multivariate models that adjusted for patient characteristics were also used to compare costs between the study and control groups. Results: Patients with epilepsy were an average age of 43 years and 57% were female. They had more co-morbidities than controls. On average, direct annual costs were significantly higher per patient with epilepsy than per control ($US10 258 vs $US3862, respectively; p < 0.0001) [year 2005 values], with an annual per-patient difference of $US6396. Epilepsy-related costs ($US2057) accounted for 20% of direct costs for patients with epilepsy. Annual indirect costs were significantly higher for employees with epilepsy than for employed controls ($US3192 vs $US1242, respectively; p < 0.0001), with a difference of $US1950. Total direct plus indirect costs for employees with epilepsy were also higher than those for employed controls ($US13 595 vs $US5338, respectively; p < 0.0001), with a difference of $US8257. Conclusions: Epilepsy was associated with significant economic burden. The excess direct costs in patients with epilepsy are underestimated when only epilepsy-related costs are considered.
TL;DR: The EQ-5D-derived QALY changes are over twice that of the SF-6D and the implication for decision makers is that cost-effectiveness evaluations for treatments in this disease class are likely to be very sensitive to the choice of utility measure.
Abstract: Background: The growth of economic analyses and in particular cost-utility analyses (CUA), which use the QALY as a measure of outcome, has heightened the interest in the methodologies used to calculate the QALY. The EQ-5D has produced quite different utility values from that of the SF-6D. This article seeks to understand these differences using a cohort of patients with inflammatory arthritis. Objective: To examine the relationship between the disease-specific measure, Health Assessment Questionnaire (HAQ) disability index (DI) and the preference-based measures, SF-6D, EQ-5D and European League Against Arthritis (EULAR) Disease Activity Score (DAS) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Methods: Patients with RA and PsA (n = 504) attending a tertiary rheumatology referral centre completed the HAQ, SF-6D and the EQ-5D before starting biological therapy and again 12 months later. The SF-36 was converted into a utility using the preference-based SF-6D. Clinical outcomes such as the DAS, joint counts and laboratory measures were also recorded. We calculated single index utility scores from the preference-based instruments using UK population norms. We used regression analysis to derive a mapping function and calculated utility scores from the HAQDI and the DAS 28. Results: The mean utility observed at baseline for RA was 0.43 for the EQ-5D and 0.54 for the SF-6D and for PsA was 0.49 for the EQ-5D and 0.57 for the SF-6D. The utility gain demonstrated by the EQ-5D was over twice that of the SF-6D. The EQ-5D scored 17% of the RA group as less than 0 (state defined as worse than death); 7% of this group remained less than 0 at followup. The distribution of the utility estimates was similar for both RA and PsA. Conclusions: Our findings draw attention to the impact of states worse than death on the overall distribution for the EQ-5D derived utilities and how these impact on its use in practice. EQ-5D-derived QALY changes are over twice that of the SF-6D. The implication of this for decision makers is that cost-effectiveness evaluations for treatments in this disease class are likely to be very sensitive to the choice of utility measure.
TL;DR: The ERG concluded that, although the evidence presented indicates that alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of alit retinoin’s efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term.
Abstract: The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with severe chronic hand eczema (CHE), as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a single-placebo randomized controlled trial (RCT) of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe CHE unresponsive to topical corticosteroids. A significantly greater proportion of patients achieved 'clear' or 'almost clear' hands by week 24 with alitretinoin than those using placebo: 48% with alitretinoin 30 mg (p < 0.001); 28% with alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who responded remained in remission during the 24-week follow-up period. The most commonly reported adverse event was dose-dependent headache, with rates of 20% in the alitretinoin 30 mg group and 11% in the alitretinoin 10 mg group, respectively. Serious adverse events were rare, although alitretinoin was associated with increases in both total cholesterol and triglycerides. No direct or indirect comparisons of alitretinoin with any of the relevant treatment comparators (psoralen + UVA [PUVA], ciclosporin or azathioprine) were available. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were pound8614 per QALY versus ciclosporin, - pound469 per QALY versus PUVA (with alitretinoin dominant) and pound10 612 per QALY versus azathioprine (year 2007-8 values). In response to a request from the ERG, the manufacturers provided a revised model that compared alitretinoin only with placebo, for which the ICER was reported to be pound12 931. However, the omission of adverse events entirely from this revised model, in combination with a number of other factors, led the ERG to conclude that the model underestimated the costs of treatment associated with alitretinoin. Estimates of health-related quality of life (HR-QOL) were the primary source of uncertainty, with the use of values from an alternative source producing ICERs of around pound30 000 per QALY gained. The ERG concluded that, although the evidence presented indicates that alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of alitretinoin's efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term. Although the ICERs estimated by the manufacturer suggested that alitretinoin may be cost effective for use in the UK NHS, utilizing the alternative HR-QOL estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable uncertainty as to the true ICER of alitretinoin versus the relevant treatment comparators. The Appraisal Committee recommended that alitretinoin be provided to those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. They recommended that treatment be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.
TL;DR: The results suggest that prospective HLA-B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care.
Abstract: Background: Abacavir sulfate (abacavir) is associated with a hypersensitivity reaction (HSR) that affects 5–8% of patients. While serious complications are rare, failure to identify it, or abacavir re-challenge following HSR, can be fatal. Genetic screening for HLA-B*5701 can identify patients who are likely to experience an HSR and reduces the incidence of the reaction. Objective: We assessed the intrinsic and practical value, from the US healthcare system perspective, of prospective HLA-B*5701 screening among a population of antiretroviral-naive patients without elevated risk factors for cardiovascular disease, plasma HIV RNA >100 000 copies/mL, or preexisting renal insufficiency. Methods: Two approaches were used to evaluate the costs and benefits of prospective screening. First, the efficiency of HLA-B*5701 screening compared with no screening prior to abacavir initiation (intrinsic value of screening) was evaluated using a 60-day decision-tree model. Next, the practical value of screening was assessed using a lifetime discrete-event simulation model that compared HLA-B*5701 screening prior to abacavir use versus initiation with a tenofovir-containing regimen. Screening-effectiveness parameters were taken from an open-label trial that incorporated screening prior to abacavir initiation and other published studies. Treatment efficacy was derived from clinical trials. Modelling assumptions, costs ($US, year 2007 values) and other parameters were derived from published sources, primary data analysis and expert opinion. Multiple one-way sensitivity and scenario analyses were performed to assess parameter uncertainty. The primary outcome measure for the short-term screening versus no screening analysis was cost per patient. For the long-term analysis, outcomes were presented as QALYs. Costs and effects were discounted at 3% per year. Results: Over the first 60 days of treatment, prospective screening prior to abacavir initiation cost an additional $US17 per patient and avoided 537 HSRs per 10 000 patients. The per-patient cost of screening was sensitive to the cost of the genetic test, HSR costs and screening performance. In the lifetime model, screening-informed abacavir use was more effective and less costly than initiation with a tenofovir-containing regimen in the base case and in sensitivity analyses. Conclusions: Our results suggest that prospective HLA-B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care.
TL;DR: Future initiatives within the Medicare programme and with private payers in the US are much more likely to succeed by relying upon the simple but consequential principles laid out at a Summit convened in Banff, Alberta, Canada in 2009.
Abstract: The concept of access with evidence development (AED), also known as 'coverage with evidence development' in the Medicare programme, has long been discussed as a policy option for ensuring more appropriate use of new technologies in the US. This article provides a comprehensive overview of more than 10 years of US experience with AED, both in the public and private healthcare sectors. Beginning with a discussion of the successes of private plans' conditional coverage for high-density chemotherapy for autologous bone marrow transplants for metastatic breast cancer and Medicare's conditional coverage of lung-volume-reduction surgery in the 1990s, the article moves on to describe how Medicare worked to codify AED as one of its coverage policy options in the early part of this decade. More recent private and public sector initiatives are also discussed, including an overview of barriers to implementing AED. Despite the complexity of political, financial and ethical issues faced in implementation, AED is now a permanent fixture of US coverage policy. Future initiatives within the Medicare programme and with private payers in the US are much more likely to succeed by relying upon the simple but consequential principles laid out at a Summit convened in Banff, Alberta, Canada in 2009 and presented in another article in this issue.
TL;DR: Although diabetes is a complex disease, several models have been developed to predict the long-term costs and consequences associated with diabetes treatment and the development of a reference case that could be used for any new diabetes models is supported.
Abstract: Diabetes mellitus is a major healthcare concern from both a treatment and a funding perspective. Although decision makers frequently rely on models to evaluate the long-term costs and consequences associated with diabetes interventions, no recent article has reviewed the methods used in long-term cost-effectiveness models of diabetes treatment. The following databases were searched up to April 2008 to identify published economic models evaluating treatments for diabetes mellitus: OVID MEDLINE, EMBASE and the Thomson's Biosis Previews, NHS EED via Wiley's Cochrane Library, and Wiley's HEED database. Identified articles were reviewed and grouped according to unique models. When a model was applied in different settings (e.g. country) or compared different treatment alternatives, only the original publication describing the model was included. In some cases, subsequent articles were included if they provided methodological advances from the original model. The following data were captured for each study: (i) study characteristics; (ii) model structure; (iii) long-term complications, data sources, methods reporting and model validity; (iv) utilities, data sources and methods reporting; (v) costs, data sources and methods reporting; (vi) model data requirements; and (vii) economic results including methods to deal with uncertainty. A total of 17 studies were identified, 12 of which allowed for the conduct of a cost-effectiveness analysis and a cost-utility analysis. Although most models were Markov-based microsimulations, models differed with respect to the number of diabetes-related complications included. The majority of the studies used a lifetime time horizon and a payer perspective. The DCCT for type 1 diabetes and the UKPDS for type 2 diabetes were the trial data sources most commonly cited for the efficacy data, although several non-randomized data sources were used. While the methods used to derive the efficacy data were commonly reported, less information was given regarding the derivation of the utilities or the costs. New interventions were generally deemed cost effective based on ten studies presenting results. Authors relied mostly on univariate sensitivity analyses to test the robustness of their models. Although diabetes is a complex disease, several models have been developed to predict the long-term costs and consequences associated with diabetes treatment. Combined with previous findings, this review supports the development of a reference case that could be used for any new diabetes models. Models could be enhanced if they had the capacity to deal with both first- and second-order uncertainty. Future research should continue to compare economic models for diabetes treatment in terms of clinical outcomes, costs and QALYs when applicable.
TL;DR: The use of cetuximab in combination with platinum-based CTX should not be recommended for the treatment of patients with recurrent and/or metastatic SCCHN and the submitted economic model was considered to be not cost effective for NICE at any price.
Abstract: The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of cetuximab (Merck Serono) to submit evidence for the clinical and cost effectiveness of cetuximab in combination with platinumbased chemotherapy (CTX) for the treatment of patients with recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN) according to the Institute’s Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERGs review of the evidence submitted by the manufacturer.Asummary of theAppraisal Committee (AC) decision is provided. The ERG reviewed the clinical evidence in accordance with the decision problem defined by NICE. The analysis of the submitted model assessed the appropriateness of the manufacturers approach to modelling the decision problem, the reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to impact substantially on the base-case cost-effectiveness results. Clinical-effectiveness evidence was derived from a single randomized controlled trial (RCT). Results presented for clinical outcomes were strongly supportive of benefits resulting from the use of cetuximab. Cetuximab + platinum-based CTX with 5 fluorouracil (5-FU) extended median overall survival (OS) from 7.4 months in the CTX group to 10.1 months in the cetuximab +CTX group. Median progression-free survival rose from 3.3months to 5.6 months, best overall response to therapy increased from 19.5% to 35.6%, disease control rate rose from60%to 81.1%andmedian time to treatment failure was 4.8 months compared with 3.0 months. Exploratory subgroup analyses indicated significant OS benefits in 11 of 16 pre-planned analyses. The ERG identified a number of issues relating to the clinical-effectiveness results: consideration was limited to first-line use of cetuximab; patients in the trial were younger and fitter than those presenting in UK clinical practice; there was no evidence of survival advantage for patients with metastatic disease; there was no evidence of effectiveness in patients not cetuximabnaive; and the quality-of-life data were poor. The submitted incremental cost-effectiveness ratio was considerably above the NICE threshold. The ERG questioned the submitted economic model on a number of grounds: the rationale for creating an economic model rather than direct analysis of trial data; the use of Weibull functions for survival models; inaccurate CTX costs; selection of health state utilities; inaccurate unit costs; and lack of mid-cycle correction. After amending the model, the ERG considered the use of cetuximab to be not cost effective for NICE at any price. The AC concluded that cetuximab in combination with platinum-based CTX should not be recommended for the treatment of patients with recurrent and/or metastatic SCCHN. Patients already receiving this treatment for this indication should have the option to continue treatment until they and their clinician consider it appropriate to stop. This was the first appraisal to consider the end-of-life medicines criteria introduced by NICE in January 2009.
TL;DR: The challenges currently facing the innovative pharmaceuticals industry are described and the history of drug development is summarized, as context for the current movement to comparative effectiveness.
Abstract: Comparative effectiveness research (CER) represents the next stage in an evolution of research and knowledge development in regard to medical interventions. In this article we describe the challenges currently facing the innovative pharmaceuticals industry and briefly summarize the history of drug development, as context for the current movement to comparative effectiveness. CER should be considered alongside the wider field of health technology assessment (HTA), and we review the status of both CER and HTA internationally and their role in health policy. Limitations as to what can be achieved with HTA and limitations to the availability of evidence of comparative effectiveness at the time of market authorization provide ongoing challenges to all stakeholders. However, embracing CER is regarded as an essential step for the innovative pharmaceutical industry, as companies strive to more clearly demonstrate the effectiveness of their pipeline products with evidence that is compelling to payers and HTA agencies. Examples are given of how these evolving requirements from regulatory and HTA agencies are impacting on drug development efforts and how one company is responding. Finally, there are signs of increasing understanding and alignment across the various partners in drug development, registration and evaluation, and further suggestions are provided for consideration as the field matures and expands.
TL;DR: The results tend to show that rituximab maintenance therapy may be a cost-effective strategy in the management of relapsed/refractory FL in France, with ICERs below those observed for other therapies in the oncology field.
Abstract: Background: Rituximab maintenance therapy was shown to significantly extend overall survival (OS) and progression-free survival (PFS) in relapsed/refractory follicular lymphoma (FL) in the pivotal EORTC 20981 trial. Objective: To assess the long-term costs and cost effectiveness of rituximab maintenance therapy after induction therapy versus current standard practice (observation) from the French National Health Service perspective. Methods: A lifetime transition model was developed comparing rituximab maintenance with observation. PFS and OS were obtained from the EORTC 20981 trial with a median follow-up of 28 months and extrapolated from 2-year Kaplan-Meier curves using a Weibull distribution. PFS and OS benefits of rituximab were conservatively assumed to last only 5 years. Utility data were obtained from a multicentre observational study using the EQ-5D questionnaire. Direct medical costs were obtained from French official sources. All costs are reported in €, year 2006 values. Results: The EORTC 20981 study demonstrated that rituximab maintenance was effective in the management of relapsed/refractory FL. The model results showed that life expectancy and QALYs were increased by 22% and 28%, respectively, in patients treated with rituximab. The incremental cost-effectiveness ratios (ICERs) were €7612 per life-year gained and €8729 per QALY gained. In a oneway sensitivity analysis,most of the ICERs fell within the range of €7000–12 000. Conclusion: The results tend to show that rituximab maintenance therapy may be a cost-effective strategy in the management of relapsed/refractory FL in France, with ICERs below those observed for other therapies in the oncology field. The cost of rituximab was partly offset by the lower cost of relapse due to a longer time in the disease-free health state for patients in the rituximab arm.
TL;DR: It is maintained in this article that CER can serve to catalyze personalized medicine, but it is recognized that researchers will need to embrace new data sources and new analytic approaches and that drug technology assessment processes will have to undergo necessary adaptations to accommodate CER.
Abstract: Comparative effectiveness research (CER) is generating intense attention as interest grows in finding new and better drug technology assessment processes. The federal government is supporting the expansion of CER through funding made available in the American Recovery and Reinvestment Act of 2009 (ARRA) and by establishing the Patient-Centered Outcomes Research Institute through the Patient Protection and Affordable Care Act of 2010. At the same time, personalized medicine is generating debate about its place in clinical medicine, and so, naturally, how CER can or cannot play a role in personalized medicine is part of these debates. At the heart of the debate around the role of CER in personalized medicine is the nature of personalized medicine and how it fits within contemporary clinical research concepts. We maintain in this article that CER can serve to catalyze personalized medicine, but we recognize that, for this to happen, researchers will need to embrace new data sources and new analytic approaches. We also recognize that drug technology assessment processes will have to undergo necessary adaptations to accommodate CER as configured for personalized medicine, and that clinicians will need to be educated appropriately and provided access to decision-support systems through health information technology to use the information coming from this research. To illustrate our argument, we describe two ongoing CER studies funded and managed in the private sector evaluating personalized medicine interventions that have important clinical and financial implications. One of the studies investigates the clinical and financial effects of pharmacogenomic testing for warfarin as prescribed in conditions of typical practice settings. The other study is also set in community practice settings and compares cardiovascular outcomes of patients receiving clopidogrel who are extensive metabolizer phenotypes for the cytochrome P450 2C19 hepatic isoenzyme with all patients receiving prasugrel.
TL;DR: The PBAC applies decision criteria equitably to cancer and noncancer drugs, in that cancer drugs are neither favoured nor disadvantaged but they are more expensive and target a smaller population than non-cancer drugs.
Abstract: Background: The hurdle of cost effectiveness for the selection and reimbursement of drugs in Australia limits access to new medicines based on an assessment of cost relative to clinical benefit. Those drugs that are expensive and provide modest benefits will be less likely to receive a government price subsidy. There is concern that the cost-effectiveness hurdle will limit access to new cancer treatments because of their high costs and modest benefits.
TL;DR: Comparing the results of economic analyses of the two agents suggests palivizumab may be the more cost-effective option in the population for which RSV prophylaxis is recommended, and major variation exists in the modelling used in these analyses.
Abstract: Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization in the US. The economic burden of severe disease is substantial, including hospitalization costs and out-of-pocket expenses. RSV prophylaxis with either RSV immune globulin intravenous (RSV-IGIV) or palivizumab has been shown to be effective in reducing RSV-related hospitalizations. Motavizumab, a new enhanced-potency humanized RSV monoclonal antibody, is presently in clinical trials. RSV-IGIV and palivizumab are associated with high acquisition costs. Cost-effectiveness analyses are therefore of great importance in helping to determine who should receive RSV prophylaxis. Six studies have analysed the cost effectiveness of RSV-IGIV, 14 have analysed the cost effectiveness of palivizumab and five have analysed the cost effectiveness of both agents, two of which directly compared palivizumab with RSV-IGIV. The cost effectiveness of motavizumab has not been studied. Significant variation exists in the modelling used in these analyses. Many studies have examined short-term benefits such as reducing hospitalizations and associated costs, while fewer studies have examined long-term benefits such as QALYs or life-years gained. The payer and society have been the most common perspectives used. The endpoints examined varied and generally did not account for the potential impact of RSV prophylaxis on RSV-related complications such as asthma. While some studies have reported acceptable cost-effectiveness ratios for RSV prophylaxis, the majority failed to show cost savings or cost-effectiveness ratios below commonly accepted thresholds for either RSV-IGIV or palivizumab. Cost effectiveness of RSV prophylaxis tended to be more favourable in populations with specific risk factors, including premature infants < or =32 weeks' gestational age, and infants or children aged < 2 years with chronic lung disease or congenital heart disease. Comparing the results of economic analyses of the two agents suggests palivizumab may be the more cost-effective option in the population for which RSV prophylaxis is recommended. Over time, the acquisition cost of RSV prophylaxis agents, a major cost driver, may decrease, and more acceptable outcomes of economic analyses may result. Albeit important, the results of economic analyses are not the only tool that decision makers rely on, as population-specific risk factors, and efficacy and safety data must be considered when developing treatment guidelines and making clinical decisions.
TL;DR: There are seven characteristics that are shared across the jurisdictions reviewed and that potentially serve as insights for development of CER in the US that must be taken into account when assessing the transferability of these insights.
Abstract: Spurred by a desire to improve quality of care and to understand the relative value of medical treatments, there has been a recent surge of interest in publicly funded comparative effectiveness research (CER) in the US. As health technology assessment (HTA) shares some of the same goals as CER, and publicly funded HTA has been a feature within other industrialized countries for many years, a review of HTA activities in some of these countries can be a helpful source of information for the US debate.