Value in Hepatitis C Virus Treatment: A Patient-Centered Cost-Effectiveness Analysis Abstract Background Innovations in hepatitis C virus (HCV) therapy included in traditional comparative evaluations focus on sustained virologic response (SVR) without addressing challenges patients report beyond virologic cure. This study aims to evaluate the cost-effectiveness of HCV drug therapy with a patient-centered approach. Methods An individual-based Markov model was constructed using guidance from a stakeholder advisory board (SAB), a patient Delphi panel, and published literature to evaluate direct-acting antivirals (DAAs) compared to no treatment. The United States (US) health sector and societal perspectives were considered for 10- and 20-year time horizons. Inputs for treatment costs and effectiveness reflect a generic regimen. Indirect costs used for the societal model included estimates from self-reported productivity in a matched-control sample. Beyond the traditional quality-adjusted life-year (QALY) health outcome, this study included two novel measures developed from the Delphi panel and SAB: infected life-years and workdays missed. All costs were measured in 2018 US dollars. Results Health sector costs and QALYs were higher in the treatment group in both 10- and 20-year models. Total infected life-years and workdays missed were reduced in the treatment group for both models. When costs of absenteeism, presenteeism, and patient/caregiver time were included, the DAA intervention was cost-saving at both 10 and 20 years. Health sector results were sensitive to drug costs and utility estimates for post-SVR health states. Societal results were sensitive to presenteeism estimates and drug costs. Conclusion Treatment was cost-effective from a health sector perspective and cost-saving when including non-health costs such as patient/caregiver time and productivity.

Correction to: Cost Effectiveness of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists, and Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: A Systematic Review CORE diabetes model was used throughout the article for consistency.

Could or Should We Use MCDA in the French HTA Process?

Acknowledgement to Referees

Performance of the UKPDS Outcomes Model 2 for Predicting Death and Cardiovascular Events in Patients with Type 2 Diabetes Mellitus from a German Population-Based Cohort Abstract Background and Objective Accurate prediction of relevant outcomes is important for targeting therapies and to support health economic evaluations of healthcare interventions in patients with diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) risk equations are some of the most frequently used risk equations. This study aims to analyze the calibration and discrimination of the updated UKPDS risk equations as implemented in the UKPDS Outcomes Model 2 (UKPDS-OM2) for predicting cardiovascular (CV) events and death in patients with type 2 diabetes mellitus (T2DM) from population-based German samples. Methods Analyses are based on data of 456 individuals diagnosed with T2DM who participated in two population-based studies in southern Germany (KORA (Cooperative Health Research in the Region of Augsburg)-A: 1997/1998, n = 178; KORA-S4: 1999–2001, n = 278). We compared the participants’ 10-year observed incidence of mortality, CV mortality, myocardial infarction (MI), and stroke with the predicted event rate of the UKPDS-OM2. The model’s calibration was evaluated by Greenwood–Nam–D’Agostino tests and discrimination was evaluated by C-statistics. Results Of the 456 participants with T2DM (mean age 65 years, mean diabetes duration 8 years, 56% male), over the 10-year follow-up time 129 died (61 due to CV events), 64 experienced an MI, and 46 a stroke. The UKPDS-OM2 significantly over-predicted mortality and CV mortality by 25% and 28%, respectively (Greenwood–Nam–D’Agostino tests: p < 0.01), but there was no significant difference between predicted and observed MI and stroke risk. The model poorly discriminated for death (C-statistic [95% confidence interval] = 0.64 [0.60–0.69]), CV death (0.64 [0.58–0.71]), and MI (0.58 [0.52–0.66]), and failed to discriminate for stroke (0.57 [0.47–0.66]). Conclusions The study results demonstrate acceptable calibration and poor discrimination of the UKPDS-OM2 for predicting death and CV events in this population-based German sample. Those limitations should be considered when using the UKPDS-OM2 for economic evaluations of healthcare strategies or using the risk equations for clinical decision-making.

Cost Effectiveness of Transplant, Conventional Chemotherapy, and Novel Agents in Multiple Myeloma: A Systematic Review Abstract Background Treatments for multiple myeloma (MM) have been rapidly evolving. Newly developed treatment regimens are likely to be more effective but also cost more than conventional therapies. Objective We conducted a systematic review to compare the cost effectiveness of different classes of MM treatment. Methods We searched the PubMed, MEDLINE, Web of Science, and EMBASE databases for studies published during 1990–2018 comparing the cost effectiveness of transplant, chemotherapeutic and novel MM treatments. Titles and abstracts were independently reviewed for eligibility by two investigators. The quality of the included studies was evaluated using the 16-item, validated Quality of Health Economics Studies instrument. Results Twenty-four publications were included in the systematic review and summarized according to treatment regimen and line. For first-line treatment, transplant was the most cost-effective option for transplant-eligible MM patients [the incremental cost-effectiveness ratio (ICER) was $4053–€45,460 per quality-adjusted life-year (QALY) gained, and $3848–$72,852 per life-year gained (LYG)], and the ICER for novel agents compared with conventional chemotherapy was $59,076 per QALY and $220,681 per LYG. For second-line treatment, in comparisons of novel agent-based regimens, ICERs were inconsistent. However, bortezomib-based regimens, lenalidomide plus dexamethasone, and pomalidomide plus dexamethasone were each cost effective compared with dexamethasone alone (ICERs showed cost saving, £30,153 per QALY gained, and €39,911 per LYG, respectively). Conclusions For transplant-eligible MM patients, transplant is a cost-effective first-line treatment. More cost-effectiveness analyses comparing novel agents in the first-line treatment regimen are warranted to determine which agent or regimen is the most cost effective. In the second-line setting, it is unclear which novel agent-based regimen is most cost effective, but bortezomib-based regimens, lenalidomide plus dexamethasone, and pomalidomide plus dexamethasone were each cost effective compared with dexamethasone alone.

A Comparison of Different Analysis Methods for Reconstructed Survival Data to Inform Cost‑Effectiveness Analysis Abstract Objectives The aim of this study was to use Microsoft Excel spreadsheet software to fit parametric survival distributions. We also explain the differences between individual patient data (IPD) and survival data reconstructed in Excel and SAS. Methods Three sets of patient data on overall survival were compared using different methods: ‘original’ IPD, ‘reconstructed SAS’, and ‘reconstructed Excel’. The best-fit distribution was selected using visual observation, supported by linear plots of predicted probabilities, goodness-of-fit coefficients, and the sum of squared error of prediction. Outcomes included the incremental cost-effectiveness ratio (ICER), incremental net benefit (INB), incremental cost, and life-years gained over short-term and lifetime horizons. These were compared for different data sets. Results In this example, log-normal, log-logistic, and Weibull distributions showed best-fit with the visual tests and goodness-of-fit statistics. Weibull and exponential distributions showed significant differences compared with IPD data. Data on short-term (5 years) time horizons produced by different data re-creation methods showed closeness with data reconstructed from SAS. The ICER and INB results were dependent on the time horizon and selected parametric distribution from the model. Conclusions Different approaches used in fitting parametric survival distributions yielded predicted probabilities that substantially differed from those using original IPD. Our study highlights the importance of following guidelines for economic evaluations with a systematic approach to parametric survival analysis techniques in order to select best fitting parametric survival distributions.

Economic Modelling of Chronic Kidney Disease: A Systematic Literature Review to Inform Conceptual Model Design Abstract Background Chronic kidney disease (CKD) is a progressive condition that leads to irreversible damage to the kidneys and is associated with an increased incidence of cardiovascular events and mortality. As novel interventions become available, estimates of economic and clinical outcomes are needed to guide payer reimbursement decisions. Objective The aim of the present study was to systematically review published economic models that simulated long-term outcomes of kidney disease to inform cost-effectiveness evaluations of CKD treatments. Methods The review was conducted across four databases (MEDLINE, Embase, the Cochrane library and EconLit) and health technology assessment agency websites. Relevant information on each model was extracted. Transition and mortality rates were also extracted to assess the choice of model parameterisation on disease progression by simulating patient’s time with end-stage renal disease (ESRD) and time to ESRD/death. The incorporation of cardiovascular disease in a population with CKD was qualitatively assessed across identified models. Results The search identified 101 models that met the criteria for inclusion. Models were classified into CKD models (n = 13), diabetes models with nephropathy (n = 48), ESRD-only models (n = 33) and cardiovascular models with CKD components (n = 7). Typically, published models utilised frameworks based on either (estimated or measured) glomerular filtration rate (GFR) or albuminuria, in line with clinical guideline recommendations for the diagnosis and monitoring of CKD. Generally, two core structures were identified, either a microsimulation model involving albuminuria or a Markov model utilising CKD stages and a linear GFR decline (although further variations on these model structures were also identified). Analysis of parameter variability in CKD disease progression suggested that mean time to ESRD/death was relatively consistent across model types (CKD models 28.2 years; diabetes models with nephropathy 24.6 years). When evaluating time with ESRD, CKD models predicted extended ESRD survival over diabetes models with nephropathy (mean time with ESRD 8.0 vs. 3.8 years). Discussion This review provides an overview of how CKD is typically modelled. While common frameworks were identified, model structure varied, and no single model type was used for the modelling of patients with CKD. In addition, many of the current methods did not explicitly consider patient heterogeneity or underlying disease aetiology, except for diabetes. However, the variability of individual patients’ GFR and albuminuria trajectories perhaps provides rationale for a model structure designed around the prediction of individual patients’ GFR trajectories. Frameworks of future CKD models should be informed and justified based on clinical rationale and availability of data to ensure validity of model results. In addition, further clinical and observational research is warranted to provide a better understanding of prognostic factors and data sources to improve economic modelling accuracy in CKD.

Value Assessment and Quantitative Benefit-Risk Modelling of Biosimilar Infliximab for Crohn’s Disease Abstract Background and Objective Regulatory approval of biosimilars often depends on extrapolating evidence from one clinical indication to all of those of the originator biologic. We aimed to develop a quantitative benefit-risk analysis to assess whether the resulting increase in the uncertainty in the clinical performance of biosimilars (i.e. risk) may be countered by their lower pricing (benefit). Methods A 1-year decision-analytic model was developed for the biosimilar infliximab (Inflectra®) for Crohn’s disease. The perspective was that of the National Health Service in the UK and costs were valued to 2015/16. A hypothetical cohort of biologic-naïve patients with moderate-to-severe Crohn’s disease was simulated through the model. Immunogenicity to infliximab was a key modifier, influencing rates of non-response and infusion reactions. Net health benefit was estimated based on quality-adjusted life-years. A range of sensitivity analyses tested the robustness of the results and explored how the biosimilar price must respond to varying immunogenicity to remain the preferred option. Results The base-case analysis predicted a positive incremental net health benefit of 0.04 (95% central range 0.00–0.09) favouring the biosimilar, based on 0.803 quality-adjusted life-years, and costs of £18,087 and £19,176 for the biosimilar and originator, respectively. Two-way sensitivity analyses suggested that if 50% of patients developed antibodies, the value-based price of £410 per vial must be lower than that of the originator (£420), but remain higher than the actual market price (£378). Conclusions The model supports the use of Inflecta® for Crohn’s disease in the UK, and provides a framework for the quantitative evaluation of biosimilars in the context of a health technology assessment. Value-based pricing using this methodology could protect health systems from the potential risks of biosimilars where they are untested in the approved populations.

The Use of Risk-Sharing Contracts in Healthcare: Theoretical and Empirical Assessments Abstract Objective The aim of this review is to provide a summary of the literature on risk-sharing agreements, including conceptual, theoretical and empirical (number of agreements and their achievements) perspectives, and stakeholders’  perceptions. Methods We conducted a systematic literature search in MEDLINE from 2000 to April 2019, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology, and completed it with a manual search of other publications (mainly grey literature). The search was restricted to publications with English abstracts; the initial identification of articles was restricted to the title, abstract and key words fields. The geographical scope was not restricted. Results Over 20 studies proposed different taxonomies of risk-sharing contracts, which can be summarised as financial and paying-for-performance agreements. Theoretical studies modelling the incentives to implement risk-sharing agreements are scarce; they addressed different types of contracts and regulatory contexts, characterizing the drug prices and the optimal strategies of the involved agents. Empirical studies describing specific agreements are abundant and referred to different geographical contexts; however, few articles showed the economic results and assessed the value of such contracts. Stakeholders’ perceptions of risk-sharing contracting were favourable, but little is known about the economic and clinical advantages of specific agreements. Whether risk-sharing contracts have yielded the desired results for healthcare systems remains uncertain. Conclusion Risk-sharing contracts are increasingly used, although the lack of transparency and aggregated registries makes it difficult to learn from these experiences and assess their impact on healthcare systems.