Published Cost-effectiveness Analyses Research Articles

OP414 The Influence Of Cost-Effectiveness Evidence And Other Factors On China's National Reimbursement Drug Listing Decisions

IntroductionChina's National Reimbursement Drug List (NRDL) covers medicines that are included in national health insurance schemes. NRDL updates take into account evidence and recommendations of experts from the fields of medicine, health economics, pharmacy and health policy. A negotiation mechanism between the government and manufacturers was introduced in 2017 to include a more detailed evaluation and negotiation for high cost drugs. However, the values that are considered in NRDL decision making are not well-understood. This study aims to investigate the influence of available evidence and other factors on coverage decisions.MethodsOutcomes of the 2017 and 2018 NRDL negotiations were analyzed. Logistic regression was used to investigate factors associated with listing decisions. Ordinary least squares and Tobit regression were used to investigate factors associated with negotiated price discounts. Independent variables were published cost-effectiveness analysis (CEA), incremental cost-effectiveness ratio (ICER), disease area, burden of disease (disability-adjusted life years), company ownership (domestic or foreign) and regulatory approval year.ResultsTwenty-eight out of sixty-two negotiated drugs had one or more published CEA studies in the English or Chinese language, although neither the presence of a study nor the central ICER estimates were predictive of price discount or listing. A longer time since regulatory approval was a significant predictor of listing (p < 0.05). Disease area (oncology) and ownership (foreign) were significant predictors of a higher price discount (p < 0.01).ConclusionsThe NRDL plays a key role in providing access to healthcare for the 95 percent of China's population that is covered by public insurance. We found several factors that were associated with reimbursement decisions. Many of the medicines in the NRDL negotiation have CEA evidence, although the role of CEA in reimbursement decision making in China remains inconclusive.

PCV60 Preliminary Budget IMPACT Analysis of Advanced Imaging and Mechanical Thrombectomy for ACUTE Ischaemic Stroke Beyond 6 Hours from Onset in the United Kingdom

Mechanical thrombectomy (MT) informed by advanced imaging (ADIM) is cost-effective up to 24 hours from acute ischaemic stroke (AIS) onset in the United Kingdom (UK). Our goal is to assess the financial impact of commissioning ADIM and MT within and beyond 6 hours from onset in the UK (compared to conventional imaging and MT within 6 hours only). We used the decision tree and Markov trace of a recently published cost-effectiveness analysis. We considered 87,078 as the average annual number of AIS patients admitted to the hospital. All suspected stroke patients were considered to be diagnosed by ADIM which was modelled with a perfect accuracy. Given the lack of evidence regarding the prior probability for an AIS patient to benefit from late MT, 3 scenarios were simulated. The UK NHS perspective was used and costs were based on the year 2018. Acute care costs and post-stroke costs indexed on the level of dependence were included. Assuming prior probabilities of 10%, 20% and 30%, the annual number of MTs performed beyond 6 hours would be 6,382, 12,765 and 19,147, respectively. At a 3-year time horizon, preliminary analyses show that the financial impact of ADIM + MT beyond 6 hours (versus conventional care within 6 hours) would be £113,320,807 (+3%), £200,898,224 (+5%) and £288,475,021 (+7%), respectively. Considering an annual NHS budget for new stroke cases of £1.6 billion, this would suggest an annual budget increase of 2.4%, 4.2% and 6%, respectively. A more precise estimate of the prior probability to benefit from late MT is needed to ascertain our preliminary results. Although ADIM and MT up to 24 hours from onset is cost-effective, it is important to assess whether the NHS can afford this intervention for all eligible patients and widespread ADIM for all suspected stroke patients countrywide.

An updated cost-effectiveness analysis of pazopanib versus sunitinib as first-line treatment for locally advanced or metastatic renal cell carcinoma in Italy

Objective To assess the cost-effectiveness of pazopanib versus sunitinib as a first-line treatment for patients with metastatic renal cell carcinoma (mRCC) from an Italian National Health Service perspective, considering the evolving Italian landscape in terms of new reimbursement agreements trend. Methods This analysis is an update of the previously published cost-effectiveness analysis to incorporate recent 2019 costs and additional changes regarding drug discounting. A partitioned-survival analysis model with three different health states (progression-free survival, post-progression survival, and dead) was utilized. Outcomes included progression-free life years, post-progression life years, overall life years, quality-adjusted life years (QALYs), and costs calculated for both treatments. Cost-effectiveness was assessed in terms of incremental costs per QALY gained and the net monetary benefit (NMB) of pazopanib versus sunitinib. In the base case analysis, a time horizon of 5 years was used and future costs and QALYs were discounted at a 3% annual discount rate. An impact of methodological and parameter uncertainly on base case results was evaluated using probabilistic and deterministic sensitivity analyses. Results In the base case, pazopanib had higher QALYs (+0.060) at lower costs (−€5,857) versus sunitinib, hence it dominated sunitinib. At willingness-to-pay thresholds of €30,000 and €50,000 per QALY, the NMB with pazopanib were €7,647 and €8,841 per patient, respectively, versus sunitinib. The probability that pazopanib is cost-effective versus sunitinib was estimated to be 97.5% at a cost-effectiveness threshold of €20,000, 95.4% at a threshold of €30,000, and 90.2% at a threshold of €50,000 per QALY. Cost-effectiveness results were robust to changes in key parameter values and assumptions as demonstrated by deterministic sensitivity analyses. Conclusions Pazopanib is likely to represent a cost-effective treatment option compared with sunitinib as a first-line treatment for patients with metastatic RCC in Italy.

Costs and where to find them: identifying unit costs for health economic evaluations of diabetes in France, Germany and Italy

BackgroundHealth economic evaluations require cost data as key inputs. Many countries do not have standardized reference costs so costs used often vary between studies, thereby reducing transparency and transferability. The present review provided a comprehensive overview of cost sources and suggested unit costs for France, Germany and Italy, to support health economic evaluations in these countries, particularly in the field of diabetes.MethodsA literature review was conducted across multiple databases to identify published unit costs and cost data sources for resource items commonly used in health economic evaluations of antidiabetic therapies. The quality of unit cost reporting was assessed with regard to comprehensiveness of cost reporting and referencing as well as accessibility of cost sources from published cost-effectiveness analyses (CEA) of antidiabetic medications.ResultsAn overview of cost sources, including tariff and fee schedules as well as published estimates, was developed for France, Germany and Italy, covering primary and specialist outpatient care, emergency care, hospital treatment, pharmacy costs and lost productivity. Based on these sources, unit cost datasets were suggested for each country. The assessment of unit cost reporting showed that only 60% and 40% of CEAs reported unit costs and referenced them for all pharmacy items, respectively. Less than 20% of CEAs obtained all pharmacy costs from publicly available sources.ConclusionsThis review provides a comprehensive account of available costs and cost sources in France, Germany and Italy to support health economists and increase transparency in health economic evaluations in diabetes.

Using informative prior based on expert opinion in Bayesian estimation of the transition probability matrix in Markov modelling\u2014an example from the cost-effectiveness analysis of the treatment of patients with predominantly negative symptoms of schizophrenia with cariprazine

BackgroundWhen patient health state transition evidence is missing from clinical literature, analysts are inclined to make simple assumptions to complete the transition matrices within a health economic model. Our aim was to provide a solution for estimating transition matrices by the Bayesian statistical method within a health economic model when empirical evidence is lacking.MethodsWe used a previously published cost-effectiveness analysis of the use of cariprazine compared to that of risperidone in patients with predominantly negative symptoms of schizophrenia. We generated the treatment-specific state transition probability matrices in three different ways: (1) based only on the observed clinical trial data; (2) based on Bayesian estimation where prior transition probabilities came from experts’ opinions; and (3) based on Bayesian estimation with vague prior transition probabilities (i.e., assigning equal prior probabilities to the missing transitions from one state to the others). For the second approach, we elicited Dirichlet prior distributions by three clinical experts. We compared the transition probability matrices and the incremental quality-adjusted life years (QALYs) across the three approaches.ResultsThe estimates of the prior transition probabilities from the experts were feasible to obtain and showed considerable consistency with the clinical trial data. As expected, the estimated health benefit of the treatments was different when only the clinical trial data were considered (QALY difference 0.0260), its combination with the experts’ beliefs were used in the economic model (QALY difference 0.0253), and when vague prior distributions were used (QALY difference 0.0243).ConclusionsImputing zeros to missing transition probabilities in Markov models might be untenable from the clinical perspective and may result in inappropriate estimates. Bayesian statistics provides an appropriate framework for imputing missing values without making overly simple assumptions. Informative priors based on expert opinions might be more appropriate than vague priors.

A Critical Appraisal and Recommendations for Cost-Effectiveness Studies of Poly(ADP-Ribose) Polymerase Inhibitors in Advanced Ovarian Cancer.

BackgroundOvarian cancer is the fifth leading cause of cancer death in women in the US. With poly(ADP-ribose) polymerase (PARP) inhibitors having shown promising results in ongoing trials, there is interest in better understanding their economic value.ObjectiveThis study aimed to review and evaluate the quality of published cost-effectiveness analyses (CEAs), and provide recommendations for CEAs in this setting.MethodsA systematic literature review of the MEDLINE and EMBASE databases was conducted in June 2019 to identify CEAs of PARP inhibitors in treating advanced ovarian cancer from peer-reviewed journals and conferences. Key information from the identified publications were extracted and reviewed. The quality of full-text studies was assessed using the Quality of Health Economic Studies instrument. Recommendations for future CEAs were developed based on the findings from the literature review.ResultsEighteen CEAs (five in full texts) met the inclusion criteria. Most adopted a US healthcare or societal perspective. The majority of the studies did not clearly display the economic model structure. No studies reported the validation of model projections based on internal or external data. Surrogate outcomes such as incremental costs per progression-free life-year gained were the most common outcomes reported. The majority of studies drew their conclusions based on surrogate outcomes, even with no theoretical or empirical threshold for cost effectiveness. All five full-text studies included some type of sensitivity or scenario analyses. The key drivers of the incremental cost-effectiveness ratio were treatment duration, effects, and costs, health utility, and prevalence of BRCA mutations.ConclusionIn the existing CEAs for PARP inhibitors, there were uncertainties and challenges leading to variation in quality. We provided recommendations to improve consistency and quality of CEAs in this setting, which will help to better understand the value of PARP inhibitors, improve decision making, and reduce potential misallocation of resources.Electronic supplementary materialThe online version of this article (10.1007/s40273-020-00949-9) contains supplementary material, which is available to authorized users.

Optimal Allocation of Research Funds under a Budget Constraint.

Purpose. Health economic evaluations that include the expected value of sample information support implementation decisions as well as decisions about further research. However, just as decision makers must consider portfolios of implementation spending, they must also identify the optimal portfolio of research investments. Methods. Under a fixed research budget, a decision maker determines which studies to fund; additional budget allocated to one study to increase the study sample size implies less budget available to collect information to reduce decision uncertainty in other implementation decisions. We employ a budget-constrained portfolio optimization framework in which the decisions are whether to invest in a study and at what sample size. The objective is to maximize the sum of the studies' population expected net benefit of sampling (ENBS). We show how to determine the optimal research portfolio and study-specific levels of investment. We demonstrate our framework with a stylized example to illustrate solution features and a real-world application using 6 published cost-effectiveness analyses. Results. Among the studies selected for nonzero investment, the optimal sample size occurs at the point at which the marginal population ENBS divided by the marginal cost of additional sampling is the same for all studies. Compared with standard ENBS optimization without a research budget constraint, optimal budget-constrained sample sizes are typically smaller but allow more studies to be funded. Conclusions. The budget constraint for research studies directly implies that the optimal sample size for additional research is not the point at which the ENBS is maximized for individual studies. A portfolio optimization approach can yield higher total ENBS. Ultimately, there is a maximum willingness to pay for incremental information that determines optimal sample sizes.

PMU14 THE USE OF PERSPECTIVE AND COSTING APPROACHES IN COST-EFFECTIVENESS ANALYSIS

To analyze perspective and costing approaches used in published cost-effectiveness analyses (CEA) and their impact on reported incremental cost-effectiveness ratios (ICERs). We analyzed Tufts Medical Center’s CEA and Global Health CEA Registries, containing 6,907 cost-per-quality-adjusted-life-year (QALY) and 709 cost-per-disability-adjusted-life-year (DALY) studies, published from 1974 to 2018. Using collected information on analytic perspective, costing methodology, and reported ICERs, we examined how often published CEAs include cost components beyond those traditionally included and investigated how the inclusion of different cost components influences cost-effectiveness ratios. A healthcare sector perspective was most prevalent (75% of cost-per-QALY and 66% of cost-per-DALY literature). Some CEAs did not clearly state the perspective used (13% of cost-per-QALY and 20% of cost-per-DALY literature). Although most studies included intervention-related medical costs, CEAs seldom included unrelated medical costs. Cost-per-DALY studies were more likely to include at least one non-healthcare cost component than cost-per-QALY studies (34% vs. 21%). The most common non-healthcare cost component was productivity in the cost-per-QALY literature (11%) and patient transportation costs in the cost-per-DALY literature (21%). CEAs rarely assessed impacts on other non-healthcare sectors, such as education or criminal justice system. Of 18,206 cost-per-QALY ratios, the median ICER was $26,000/QALY (inter-quartile range, IQR:3,100-100,000), while 18% of ratios were cost-saving. Of 4,994 cost-per-DALY ratios, the median ICER was $440/DALY (IQR:75-3,400), while 7% of ratios were cost-saving. Among cost-per-QALY ratios calculated from a healthcare sector perspective, the median ICER ($25,000/QALY, IQR:3,100-100,000), was lower than the corresponding median from a societal perspective ($30,000/QALY, IQR:2,300-150,000). Non-industry sponsored studies reported higher ICERs than industry-sponsored studies from both perspectives. Key study attributes, including perspective and cost components, vary substantially in the CEA literature. Researchers and analysts should be transparent about their choices. Revised guidelines by the Second Panel, such as the inclusion of an Impact Inventory, help to reduce inconsistencies across studies and confusion.

Adherence to Discounting Guidelines: Evidence from Over 2000 Published Cost-Effectiveness Analyses.

Previous studies have shown that not all cost-effectiveness analyses (CEAs) adhere to recommended guidelines on intertemporal discounting. This analysis investigates adherence in a sample of over 2000 CEAs from seven countries. Guideline discount rates were retrieved for Australia, Belgium, Canada, Ireland, The Netherlands, New Zealand and the UK. Data on the rates applied in published CEAs were retrieved from the Tufts CEA Registry from the sample countries within the periods covered by the discounting guidelines. The relationship between adherence and candidate explanatory factors were assessed using logistic regression. The analysis appraised 2270 CEAs. The overall rate of adherence to discounting recommendations was 79%. Country-specific adherence ranged from 28% in New Zealand to 87% in Belgium and the UK. Adherence in Australia and Canada was 73% and 66%, respectively. Adherence is statistically significantly higher in more recent studies, countries currently applying differential discounting and manufacturer-sponsored studies. Relative to the reference case of Australia, adherence is statistically significantly higher in the UK and lower in Canada and New Zealand. There is notable variation in the rates of adherence to discounting recommendations between countries and over time. Incomplete adherence raises concerns regarding the comparability of evidence between studies. In turn, this raises concerns regarding equity of access to scarce healthcare resources. Journal editors should ensure that adherence to discounting recommendations is assessed as part of the peer review process.

Are Lifestyle Interventions to Reduce Excessive Gestational Weight Gain Cost Effective? A Systematic Review.

Lifestyle interventions (such as diet and physical activity) successfully limit excessive gestational weight gain and can reduce some adverse maternal events; however, benefit is variable and cost-effectiveness remains unclear. We aimed to review published cost-effectiveness analyses of lifestyle interventions compared with usual care on clinically relevant outcome measures. Five international and six grey-literature databases were searched from 2007 to 2018. Articles were assessed for quality of reporting. Data were extracted from healthcare and societal perspectives. Costs were adapted to the common currencies of Australia and the United Kingdom by adjusting for resource utilization, healthcare purchase price and changes in costs over time. Included studies were economic analyses of lifestyle interventions aiming to limit weight-gain during pregnancy and/or reduce risk of gestational diabetes, for women with a BMI of 25 or greater in pre- or early-pregnancy. Of the 538 articles identified, six were retained for review: one modelling study and five studies in which an economic analysis was performed alongside a randomized-controlled trial. Outcome measures included infant birth-weight, fasting glucose, insulin resistance, gestational weight-gain, infant respiratory distress syndrome, perceived health, cost per case of adverse outcome avoided and quality-adjusted life years (QALYs). Interventions were cost-effective in only one study. Although many studies have investigated the efficacy of lifestyle interventions in pregnancy, few have included cost-effectiveness analyses. Where cost-effectiveness studies were undertaken, results were inconsistent. Secondary meta-analysis, taxonomy and framework research is now required to determine the effective components of lifestyle interventions and to guide future cost-effectiveness analyses.

One-Way Sensitivity Analysis for Probabilistic Cost-Effectiveness Analysis: Conditional Expected Incremental Net Benefit.

Although probabilistic analysis has become the accepted standard for decision analytic cost-effectiveness models, deterministic one-way sensitivity analysis continues to be used to meet the need of decision makers to understand the impact that changing the value taken by one specific parameter has on the results of the analysis. The value of a probabilistic form of one-way sensitivity analysis has been recognised, but the proposed methods are computationally intensive. Deterministic one-way sensitivity analysis provides decision makers with biased and incomplete information whereas, in contrast, probabilistic one-way sensitivity analysis (POSA) can overcome these limitations, an observation supported in this study by results obtained when these methods were applied to a previously published cost-effectiveness analysis to produce a conditional incremental expected net benefit curve. The application of POSA will provide decision makers with unbiased information on how the expected net benefit is affected by a parameter taking on a specific value and the probability that the specific value will be observed.

Cost-Effectiveness Analysis in Pediatric Imaging: The Evidence (or Lack Thereof) Thus Far.

To systematically review all published cost-effectiveness analyses (CEAs) of imaging technologies in children. We identified all CEAs involving fetal and pediatric imaging included in a publicly available repository of CEAs published since 1976. Information on publication characteristics, methods, costs, quality of life weights, and incremental cost-effectiveness ratios (ICERs) was recorded for each article. Of 480 diagnostic CEAs, only 10 focused on fetal and pediatric imaging. The 10 studies reported 43 quality of life weights based on previously published adult data (n= 20, 46.5%); pregnant women perspective (n= 11, 25.6%), and treating physician perspective (n= 12, 27.9%). None of the studies elicited quality of life weights from children nor took into consideration the postnatal impact of disease on family's quality of life. All studies used a health care payer perspective without incorporating patients' incurred cost such as loss wages or travel related cost. Of 37 ICERs, 7 (18.9%) were cost saving and 6 (16.2%) were more expensive and less effective. The remaining ICERs ranged from $1,400 per quality-adjusted life-year (MRI versus ultrasound in newborns with moderate risk of occult spinal dysraphism) to $10,000,000 per quality-adjusted life-year (CT versus no imaging in children at low risk for craniosynostosis). There is a striking paucity of cost-effectiveness studies evaluating imaging technologies in children. Existing studies do not incorporate the patient and family perspectives regarding utilities (eg, impact of child's disease on families' quality of life) or cost (eg, loss wages, travel, time off). Future studies should elicit and incorporate the impact of disease on families to better reflect real-world scenarios.

PNS60 CAN WE APPLY NICE COST-EFFECTIVENESS TO FRENCH EFFICIENCY OPTIONS: A COMPARISON OF SEVEN NICE AND HAS BASECASE COST-EFFECTIVENESS SCENARIOS

To describe the impact of hypotheses and parameters in national institute for health and care excellence (NICE) and the health economic and public health commission (CEESP) of the french health autority (HAS) appraisals, on the incremental cost-effectiveness ratios (ICER) of six pharmaceutical products with a total of seven treatment indications with published cost-effectiveness analyses from both NICE and CEESP. In order to measure the impact of choices made by NICE and the CEESP on ICERs, we compared first final NICE and CEESP’s appraisals for seven indications with a focus on: methodology of analysis, time horizon, discount rates, extrapolation of clinical efficacy, sources of utility, adverse events. The analysis of the models revealed differences in the seven evaluations submitted to NICE and the CEESP. Some of these differences have an impact easy to interpret: longer time horizons and a slightly lower discount rate (3.5% vs 4.0%) were adopted in NICE submissions which individually tend to lower ICERs. Other differences regarding methodological choices are more difficult to handle when it comes to compare the ICERs, especially in the choice of comparators in five evaluations, survival extrapolation in four evaluations, model structure (semi-Markov vs partitioned survival) in two evaluations, population in two evaluations and method of estimation of adverse event in two evaluations. In order to evaluate the feasibility of comparing methodological choices used in NICE and CEESP appraisals, it is important to adapt the models to quantify the impact on ICERs. Finally, the differences regarding parameters and methodological choices used in the seven evaluations by NICE and CEESP submission showed that NICE’s choices were more favorable regarding the ICER 6 times out of 7.

Cost-effectiveness of smoking cessation programs for hospitalized patients: a systematic review.

This systematic review examined the characteristics of published cost-effectiveness analyses of inpatient smoking cessation programs and assessed the methodological quality of the selected studies, to provide policymakers with economic evidence for this type of program. A literature search was undertaken using a relevant database by three investigators. Only full economic evaluations with results in the form of the incremental cost-effectiveness ratio (ICER) were included. Costs were adjusted to 2016 US dollars using the Gross Domestic Product deflator and purchasing power parities. The British Medical Journal checklist was utilized to appraise the methodological quality of the included studies. Nine articles were ultimately selected. The inpatient smoking cessation programs appeared to be a highly cost-effective intervention according to the recommended cost-effectiveness thresholds by the World Health Organization or individual studies. The highest ICERs among the selected studies were $5593 per additional quit, $10,550 per life year gained, and $5680 per quality-adjusted life year gained. This study provides robust evidence supporting the cost-effectiveness of smoking cessation programs for hospitalized patients. In addition, the results indicated that the degree of cost-effectiveness of the inpatient smoking cessation program might not be related to either the components of the program or methodological variations in the cost-effectiveness analysis. Policymakers should provide hospitals with resources and strong incentives to promote wider implementation of the smoking cessation program.

Cost-Effectiveness of Sacubitril/Valsartan in Germany: An Application of the Efficiency Frontier

BackgroundTo assess the cost-effectiveness of new treatments in Germany, the efficiency frontier (EF) method has been developed. We compared the cost-effectiveness analysis using international standards and the German methodology, using the heart failure drug sacubitril/valsartan as an example. MethodsA previously developed Markov model was adapted to include 4 treatment options: no treatment, enalapril, candesartan, and sacubitril/valsartan. The internationally used incremental cost-effectiveness ratio (ICER) was calculated, as well as cost-effectiveness acceptability curves. Additionally, EFs, net monetary benefits (NMBs), and price-acceptability curves were created according to German guidelines. All analyses were performed from the perspective of the German Statutory Health Insurance. ResultsThe base-case ICER for sacubitril/valsartan compared to enalapril is €19 300/quality-adjusted life-year. On the cost-effectiveness acceptability curve, sacubitril/valsartan is most likely to be cost-effective, out of all included comparators, from a hypothetical willingness-to-pay threshold of €18 250/quality-adjusted life-year onward. No EF could be constructed for the base case. Taking the uncertainty of the input parameters into account for the probabilistic sensitivity analysis, a NMB of around −€14 000 was calculated, depending on the outcome considered, with the NMB being zero at a daily price for sacubitril/valsartan ranging from €1.52 to €1.67. ConclusionWe calculated an ICER for Germany, comparable to previously published cost-effectiveness analyses for Europe, which widely concluded sacubitril/valsartan to be cost-effective. Using the German EF approach, a considerable discount needs to be applied before sacubitril/valsartan can be considered cost-effective.

Toward Relevant and Credible Cost-Effectiveness Analyses for Value Assessment in the Decentralized U.S. Health Care System.

In the United States, there is an increased interest to understand the value of health technologies. Cost-effectiveness analysis is arguably the most appropriate framework to quantify value and to inform reimbursement decision making regarding medical interventions; however, a thorough analysis is resource intensive and complex. In many countries, the cost-effectiveness of medical interventions is evaluated by expert agencies at the national level, but in the United States, reimbursement decision making occurs at the local level. This raises the question of how we can provide a means to transparent cost-effectiveness analysis that reflects the local context and patient population and is based on the latest evidence and scientific insights. In other words, how can we maximize the relevance and credibility of cost-effectiveness evaluations in the context of a decentralized decision-making environment? Published cost-effectiveness analyses typically fail on these dimensions. Access to transparent open-source models that can be adapted to reflect the local setting in a relatively straightforward manner is an essential step toward such a goal. However, no model for cost-effectiveness analysis is ever truly "right" or "complete," and it must evolve along with clinical evidence and improvements in scientific methodology to ensure that its credibility remains. We propose a transparent approach of iterative development and collaboration between content and methodology experts to produce up-to-date, open-source consensus-based cost-effectiveness models that account for parameter and structural uncertainty to help local decision makers understand the confidence with which they might make a decision. Our proposed approach provides a way to adapt formal assessments of value-long the province of centralized health care systems-into the decentralized U.S. health care landscape. DISCLOSURES: This research was funded through the Innovation and Value Initiative, a nonprofit multistakeholder research organization. The Innovation and Value Initiative contracted with Precision Medicine Group for research activities related to this article. Jansen and Incerti are salaried employees and shareholders of Precision Medicine Group. Curtis is a paid consultant for the Innovation and Value Initiative. Curtis also reports consulting fees and grants from Amgen, AbbVie, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, Radius, and UCB, unrelated to this article.

Future of Patients in Healthcare Evaluation: The Patient-Informed Reference Case

The “Reference Case” was developed to facilitate comparability among published cost-effectiveness analyses intended to contribute to decisions about the broad allocation of healthcare resources. Although the societal perspective is recommended for Reference Case analyses, empirical estimations rarely adequately represent the patient perspective, and more often, healthcare system or payer perspectives are used. In this commentary, we discuss the evolution of the Reference Case over the past 20 years and how it now needs to further evolve. This should begin with a patient-informed societal perspective. A realignment of the societal perspective to better include patient perspectives in CEA creates a conduit for patient inclusion. Engaging patients to both derive patient-informed value elements and prioritize value elements using stated preference methods will lead to patient inclusion in the societal perspective and a patient-informed Reference Case analysis.

OP34 One-Way Sensitivity Analysis For Cost Effectiveness Analysis

IntroductionAlthough stochastic analysis has become the accepted standard for decision analytic cost effectiveness models, deterministic one-way sensitivity analysis continues to be used to meet the needs of decision makers to understand the impact that changing the value taken by one specific parameter has on the results of the analysis. However, there are a number of problems with this approach.MethodsWe review the reasons why deterministic one-way sensitivity analysis will provide decision makers with biased and incomplete information. We then describe a new method - stochastic one-way sensitivity analysis (SOWSA), and apply this to a previously published cost effectiveness analysis, to produce a stochastic tornado diagram and conditional incremental net benefit curve. We then discuss how these outputs should be interpreted and the potential barriers to the implementation of SOWSA.ResultsThe results illustrate the shortcomings of the current approaches to deterministic one-way sensitivity analysis. For SOWSA, the expected costs and outcomes are captured, along with the sampled value of the parameter and these are linked to the probability that the parameter takes that value – which can be read off the probability distribution for the parameter used in the stochastic analysis. From these results it is possible to gain insights into probability that a parameter will take a value that will change a decision.ConclusionsAlthough a well-used technique, one-way deterministic sensitivity analysis has a number of shortcomings that may contribute to incorrect conclusions being drawn about the importance of certain parameter values on model results. By providing fuller information on uncertainty in model results, it is hoped that the methods here will lead to more informed decision making. Although, as with all developments in the presentation of analytic results to decision makers, care will be required to ensure that the decision makers understand the information provided to them.

A Systematic Review of Cost-Effectiveness Analyses of Left Ventricular Assist Devices: Issues and Challenges.

Advanced heart failure (HF) can be treated conservatively or aggressively, with left ventricular assist devices (LVADs) and heart transplant (HT) being the most aggressive strategies. The goal of this review was to identify, describe, critique and summarize published cost-effectiveness analyses on LVADs for adults with HF. We conducted a literature search using PubMed and ProQuest DIALOG databases to identify English-language publications from 2006 to 2017 describing cost-effectiveness analyses of LVADs and reviewed them against inclusion criteria. Those that met criteria were obtained for full-text review and abstracted if they continued to meet study requirements. A total of 12 cost-effectiveness studies (13 articles) were identified, all of which described models; they were almost evenly split between those examining LVADs as destination therapy (DT) or as bridge to transplant (BTT). Studies were Markov or semi-Markov models with one- or three-month cycles that followed patients until death. Inputs came from a variety of sources, with the REMATCH trial and INTERMACS registry common clinical data sources, although some publications also used data from studies at their own institutions. Costs were derived from standard sources in many studies but from individual hospital data in some. Inputs for health utilities, which were used in 11 of 12 studies, were generally derived from two studies. None of the studies reported a societal perspective, that is, included non-medical costs such as caregiving. No study found LVADs to be cost effective for DT or BTT with base case assumptions, although incremental cost-effectiveness ratios met thresholds for cost effectiveness in some probabilistic analyses. With constant improvements in LVADs and expanding indications, understanding and re-evaluating the cost effectiveness of their use will be critical to making treatment decisions.

PGI23 - COST-EFFECTIVENESS ANALYSIS OF PARENTERAL METHOTREXATE FOR THE TREATMENT OF CROHN’S DISEASE IN THE CZECH REPUBLIC

Clinical evidence suggests that parenteral methotrexate (MTX) provides benefit for induction of remission and complete discontinuation of high-dose oral corticosteroid treatment (hdCS; >20mg/day) in patients with Crohn’s disease (CD). Our aim was to assess cost-effectiveness of MTX in the treatment of mild-to-moderate CD in comparison to hdCS/placebo with its gradual withdrawal in the Czech Republic. We developed a three-year Markov model with one-week cycle length in TreeAge. The model comprises four health states – initial state of mild-to-moderate CD (16-week treatment with MTX or hdCS), steroid-free remission, lack/loss of response and death. It projects quality-adjusted life-years (QALYs) and costs from healthcare payers’ perspective. Costs were based on list prices, reimbursement tariffs and previous pharmacoeconomic analyses as of 02/2018. Costs and outcomes were discounted by 3%. Transition probabilities between health states were provided by clinical trials and extrapolated using survival analysis. Mortality rate was taken from Czech mortality tables and adjusted to CD. Utilities were derived from the published mapping algorithm. One-way sensitivity analysis (OWSA) accompanied by scenario analysis (SA) was performed. Probability sensitivity analysis (PSA; 10,000 iterations) was run using an implicit willingness-to-pay threshold (WTP) of €47,000/QALY. Over a three-year time horizon, MTX yields additional 0.06 QALYs (1.92 vs. 1.86) at the additional total cost of €761 (€2263 vs. €1503) compared with hdCS, with the incremental cost-effectiveness ratio of €13,077/QALY. PSA showed that probability of MTX to be cost-effective was 99.89% at the WTP. OWSA and SA confirmed the robustness of the base-case result with all one-way changes and scenarios deeply below WTP. Parenteral MTX is a cost-effective therapy for patients with mild-to-moderate CD receiving hdCS. Therefore, it was swiftly and positively assessed by the local authority. To our knowledge, this is the first published cost-effectiveness analysis of parenteral MTX for this indication.