Cost- Effectiveness of Avatrombopag for the Treatment of Thrombocytopenia in Patients with Chronic Liver Disease.

BACKGROUND AND AIM: Thrombocytopenia is common in people with chronic liver disease, who frequently undergo invasive procedures. To minimize the risk of bleeding, prophylactic platelet transfusions have traditionally been used but carry many risks. The aim of this study was to evaluate the cost-effectiveness of avatrombopag compared with platelet transfusion and lusutrombopag as a treatment for thrombocytopenia in adult patients with chronic liver disease scheduled to undergo a medical procedure. METHODS: A decision-tree model was developed from a US payer perspective to capture acute events observed in phase 3 global randomized controlled clinical trials and, to support exploratory analyses, potential longer-term complications resulting from a major bleed or thromboembolic event. Treatment costs were taken from publicly available data sources. The interventions were evaluated in the overall trial populations and in subpopulations with higher and lower baseline platelet counts. Results were presented as incremental cost per platelet transfusion avoided. One-way and probabilistic sensitivity analyses were conducted. RESULTS: In the overall population, avatrombopag reduced the need for platelet transfusions and produced cost-savings compared with platelet transfusion (80% fewer prophylactic platelet transfusions, $4250 lower costs) and lusutrombopag (42% fewer prophylactic platelet transfusions, $5819 lower costs). Similar results were seen in both the higher and lower platelet count subpopulations. The one-way and probabilistic sensitivity analyses found that the use of avatrombopag is cost-saving with the incremental cost-effectiveness ratio in quadrant IV (decreased costs, prophylactic platelet transfusions avoided). CONCLUSION: The use of avatrombopag is expected to be cost-saving while reducing the need for prophylactic platelet transfusions compared with platelet transfusion and lusutrombopag.

The impact of timing and prioritization on the cost-effectiveness of birth cohort testing and treatment for hepatitis C virus in the United States.

UNLABELLED: Recent United States guidelines recommend one-time birth cohort testing for hepatitis C infection in persons born between 1945 and 1965; this represents a major public health policy undertaking. The purpose of this study was to assess the role of treatment timing and prioritization on predicted cost-effectiveness. The MONARCH hepatitis C lifetime simulation model was used in conjunction with a testing and treatment decision tree to estimate the cost-effectiveness of birth cohort versus risk-based testing incorporating information on age, fibrosis stage and treatment timing. The study used a 1945-1965 birth cohort and included disease progression, testing and treatment-related parameters. Scenario analysis was used to evaluate the impact of hepatitis C virus (HCV) prevalence, treatment eligibility, age, fibrosis stage and timing of treatment initiation on total costs, quality-adjusted life years (QALYs), HCV-related complications and cost-effectiveness. The cost-effectiveness of birth cohort versus risk-based testing was $28,602. Assuming 91% of the population is tested, at least 278,000 people need to be treated for birth cohort testing to maintain cost-effectiveness. Prioritizing treatment toward those with more advanced fibrosis is associated with a decrease in total cost of $7.5 billion and 59,035 fewer HCV-related complications. Total QALYs and complications avoided are maximized when treatment initiation occurs as soon as possible after testing. CONCLUSION: This study confirms that birth cohort testing is, on average, cost-effective. However, this remains true only when enough tested and HCV-positive subjects are treated to generate sufficient cost offsets and QALY gains. Given the practical and financial challenges associated with implementing birth cohort testing, the greatest return on investment is obtained when eligible patients are treated immediately and those with more advanced disease are prioritized.

Assessing the cost utility of response-guided therapy in patients with chronic hepatitis C genotype 1 in the UK using the MONARCH model.

BACKGROUND: European guidelines advocate the measurement of on-treatment hepatitis C virus (HCV) RNA in order to determine optimal therapy duration (response-guided therapy [RGT]) in patients with rapid virological response (RVR) or delayed virological response (DVR). Treatment response is highly dependent upon the extent of liver fibrosis yet there is little evidence quantifying the cost effectiveness of RGT particularly conditional upon fibrosis stage. OBJECTIVE: This study describes an economic model designed to assess the costs and benefits of RGT compared with standard duration of therapy (SDT) in hepatitis C virus genotype 1 patients. METHODS: A Markov cohort simulation model with lifetime perspective was developed to undertake a cost utility analysis of RGT in the UK. Patients entered the model at Metavir disease stages F0-F4, and progressed through these stages via age and duration of HCV infection-dependent transition probabilities. Treated patients were partitioned according to virological response and shortened or extended duration of therapy was applied following European guidelines. RESULTS: For all patients, SDT and RGT was associated with an increase of 2.14 and 2.20 QALYs and £2,374 and £2,270 costs, respectively, compared with no treatment. Overall, RGT was a dominant scenario being associated with a lower risk of complications, increased QALYs (0.08) and cost saving (£101). RGT across fibrosis stages was either highly cost effective or dominant; in all cases RGT was associated with an increase in QALYs, driven by a reduction in complications in DVR subjects and reduced exposure to treatment disutility in RVR subjects; costs were lower in F1 and F2 fibrosis stages. At a willingness-to-pay threshold of £20,000 per QALY, overall RGT across fibrosis stages F2-F4 were associated with the highest probability of being cost effective. At this threshold, the probability of reduced/extended therapy in RVR/DVR patients being cost effective is 0.35 and 0.88, respectively. CONCLUSIONS: This analysis suggests that the treatment of HCV genotype 1 patients in fibrosis stage F2 has the greatest potential for maximizing health benefit and cost saving within an RGT protocol. Predicting those patients most likely to respond to treatments is important from both a clinical and cost perspective and the tailoring of treatment duration with the current standard of care is likely to remain a priority for payers with budgetary constraints.

Structural frameworks and key model parameters in cost-effectiveness analyses for current and future treatments of chronic hepatitis C.

OBJECTIVES: Published economic evaluations have reported available treatments for chronic hepatitis C to be cost-effective as part of the current approach to disease management, but as standards of care evolve, their approach to modeling should be reconsidered. This study aimed to review structural frameworks and key model parameters as reported in current economic evaluations for treatments for chronic hepatitis C, and model the impact of variability across parameters on results. METHODS: A systematic review of studies published from 2000 to 2011 was performed. Studies were retrieved from five electronic databases using relevant search strategies. Model structures, disease progression rates, utilities, and costs were extracted from included studies, and were qualitatively reviewed and incorporated into a cost-utility model. RESULTS: Thirty-four studies were appropriate for data extraction. A common pathway of six disease states was identified. In some studies the early disease stages and/or the decompensated cirrhosis state were further subdivided. Large variability in values used for disease progression rates, utilities, and costs were identified. When incorporated into a model, incremental cost-effectiveness ratios (ICERs) varied: in the least favorable scenario, peginterferon plus ribavirin was dominated by interferon plus ribavirin; and in the most favorable scenario, peginterferon plus ribavirin dominated interferon plus ribavirin ($8,544 per quality-adjusted life year [QALY]; costs are given in 2008 US dollar amounts). Using mean values the ICER was $15,198 per QALY. CONCLUSIONS: Current models use a simplistic structure resulting from the lack of available data reflecting patient heterogeneity. Key model parameters are currently based on a small number of studies and the variability across these values can affect the interpretation of results.

Model for end-stage liver disease (MELD) and allocation of donor livers.

BACKGROUND & AIMS: A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list. METHODS: The MELD model predicts liver disease severity based on serum creatinine, serum total bilirubin, and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis. In this study, we prospectively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant candidates with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November, 1999, and December, 2001. RESULTS: In this study cohort with chronic liver disease, 412 (12%) died during the 3-month follow-up period. Waiting list mortality increased directly in proportion to the listing MELD score. Patients having a MELD score <9 experienced a 1.9% mortality, whereas patients having a MELD score > or =40 had a mortality rate of 71.3%. Using the c-statistic with 3-month mortality as the end point, the area under the receiver operating characteristic (ROC) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh (CTP) score (P < 0.001). CONCLUSIONS: These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers.