***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract : We evaluated the costs and the cost utility of high‐dose melphalan and autologous stem cell support followed by interferon maintenance relative to conventional treatment with melphalan and prednisone , in patients less than 60 yr of age with multiple myeloma . From March 1994 to July 1997 , 274 patients with newly diagnosed , symptomatic multiple myeloma were enrolled in a prospect i ve , non‐r and omized , population ‐based , multicenter study to evaluate the treatment with high‐dose melphalan and autologous blood stem cell support .  Health‐related quality ‐of‐life was measured prior to treatment and during follow‐up , using the EORTC QLQ‐C30 question naire . Re source consumption was also recorded prospect ively . The intensive treatment yielded a significant increase in median survival time from 44 to 62 months compared to conventionally treated patients . The corresponding gain in quality ‐adjusted life years ( QALY ) was found to be 1.2 . Cost per QALY gained by the treatment with high‐dose melphalan and autologous blood stem cell support was estimated at NOK 249,000 ( USD 27,000 ) The addition of rituximab to cyclophosphamide , vincristine and prednisolone ( CVP ) for advanced follicular lymphoma increases median time to progression by 17 months . A US societal cost-effectiveness of R-CVP versus CVP is estimated for a representative 50-year-old patient .  Progression-free survival ( PFS ) and overall survival are based on a r and omized Phase III trial . Costs are estimated using Medicare reimbursement rates and published drug price data , and include drug and administration costs , adverse events , treatment of relapses , and end-of-life care . Utility estimates are derived from the literature and a 3 % discount rate is employed . Mean overall survival is projected to be 1.51 years longer for patients assigned to R-CVP versus CVP . The cost per quality -adjusted year of life gained is $ 28,565 . The utility associated with stable or progressive disease and the unit drug cost of rituximab most influence the findings . The cost-effectiveness ratio of R-CVP compared with CVP is projected to be cost-effective in the United States under a range of sensitivity analyses OBJECTIVES To evaluate the cost-effectiveness of bendamustine compared with chlorambucil as first-line treatment for patients with chronic lymphocytic leukemia who would be considered unsuitable for treatment with fludarabine combination chemotherapy regimens . METHODS A semi-Markov approach was used to estimate time in each health state . The model was parameterized primarily by using data from a phase III r and omized , open-label trial comparing bendamustine with chlorambucil . It captured the increased progression-free survival and improved response rates with bendamustine , and the cost and quality of life impacts of postprogression treatments . The analysis was conducted from the perspective of the National Health Service in Engl and and Wales . A lifetime ( 35-year ) time horizon was used . Deterministic sensitivity analyses , probabilistic sensitivity analyses , and subgroup analyses in older patients and patients with poor performance status were carried out . RESULTS The estimated incremental cost-effectiveness ratio was £ 11,960 per quality -adjusted life-year . None of the deterministic sensitivity analyses increased the incremental cost-effectiveness ratio by more than £ 2000 . Subgroup analyses showed that bendamustine remained cost-effective across different patient groups . Probabilistic sensitivity analysis showed that at the £ 20,000 threshold , bendamustine has a 90 % probability of being cost-effective . CONCLUSIONS Bendamustine represents good value for first-line treatment of patients with chronic lymphocytic leukemia who are unsuitable for treatment with fludarabine combination chemotherapy .  The incremental cost-effectiveness ratio is below the thresholds commonly applied in Engl and and Wales ( £ 20,000-£ 30,000 per quality -adjusted life-year ) The French Chronic Myeloid Leukemia Study Group prospect i ve r and omized study results indicate that the addition of cytarabine to alpha interferon ( IFN-α ) increases the rate of major cytogenetic response and prolongs survival in patients with early chronic phase chronic myelogenous leukemia ( CML ) . The French group study design permitted a single crossover to include or discontinue cytarabine or interferon . Endpoints were overall survival , complete hematologic remission ( CHR ) at six months , and major cytogenetic response at 12 months . We modified a published Markov model that compared IFN-α alone to IFN-α plus cytarabine and included the possibility of crossover as in the French study . The model permits allogeneic and autologous stem cell transplantation ( SCT ) , and follows cytogenetic response and acceleration of CML through death . Treatment response , toxicity , and survival are drawn from the French Chronic Myeloid Leukemia Study Group population of 810 patients on an intention-to-treat model . Survivals are extended to 62 months based on currently available follow-up . Costs from a United States oncology specialty institution , and state utilities from previous research and a quality -adjusted Time Without Symptoms or Toxicity analysis of the subject study were discounted at 3 % per annum . At the median cohort age of 50 , cytarabine offers 21 months of added median survival  to IFN-α , which itself is superior to conventional chemotherapy by 21 months . Cost-effectiveness estimates  for cytarabine added to IFN-α range from $ 7,000 per quality -adjusted life year ( QALY ) to $ 35,000 per QALY , under all plausible assumptions superior to IFN-α alone . The model is sensitive to the quality of life on therapy , as well as to remission rate with additive cytarabine , although the cost-effectiveness calculations are robust over the entire range of clinical assumptions . Based on data from the French study , cytarabine added to IFN-α substantially improves the cost-effectiveness of initial therapy for early chronic phase CML Editors ' Notes Context Newly approved drug regimens for hepatitis C virus ( HCV ) treatment seem more efficacious and safer than older regimens but are expensive . Contribution In a cost-effectiveness analysis , combination therapy with sofosbuvir and ledipasvir reduced HCV-related complications and was cost-effective for most patients . However , its use would cost an additional $ 65 billion over the next 5 years while off setting only $ 16 billion of the overall cost of HCV care . Caution Not all data came from large r and omized trials . Implication If prices remain at current levels , government and private providers will need additional financial re sources or will need to prioritize patients for HCV treatment . More than 3 million persons are chronically infected with hepatitis C virus ( HCV ) in the United States , and most of them are undiagnosed ( 1 , 2 ) . Infection with HCV is the leading cause of hepatocellular carcinoma ( HCC ) and is the most common indication for liver transplantation ( 3 ) . In 2011 , the economic burden associated with chronic HCV infection in the United States was $ 6.5 billion ( 4 ) . The recent approval of 3 new drugssofosbuvir , a first-in-class , once-daily HCV RNA polymerase inhibitor ; simeprevir , a once-daily protease inhibitor ; and sofosbuvir plus ledipasvir , the first oral combination therapyby the U.S. Food and Drug Administration ( FDA ) marked the beginning of a new era for HCV treatment ( 57 ) . Until then , the old st and ard of care ( oSOC ) was based on peginterferon and ribavirin with or without boceprevir and telaprevir . With the advent of the new drugs , HCV treatment can for the first time be provided without interferon-based therapy , which is associated with considerable toxicity ( 8) . As a result , many patients who were unable to tolerate previous therapies are now eligible for HCV treatment . These agents are superior , with sustained virologic response ( SVR ) rates greater than 95 % in most patients and shorter duration of treatment and fewer adverse effects than the oSOC ( 9 , 10 ) . To guide clinicians , the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America jointly published a practice guideline with new recommendations for HCV treatment as a Web document with plans for ongoing up date s ( 11 ) . These recommendations include FDA -approved as well as off-label drug combinations of sofosbuvir and ledipasvir . Enthusiasm for the new drugs has been dampened by their cost : Sofosbuvir is currently priced at $ 1000 per day and sofosbuvirledipasvir at $ 1125 per day . The total cost of treatment can be as high as $ 150000 per patient . The high price of sofosbuvir has drawn criticism from patient advocates ( 12 ) , U.S. lawmakers ( 13 ) , the World Health Organization ( 14 ) , and private payers ( 15 ) , especially given that its manufacturing cost is $ 200 for 12-week treatment ( 16 ) . Challenged with the budget needed to treat all patients with HCV , at least 35 U.S. states have restricted these treatments to Medicaid patients with advanced-stage disease ( 17 ) . Similarly , private payers require prior authorization . With more than a million patients needing HCV treatment in the next 3 to 5 years in the United States , the high price of these drugs will substantially affect the budget of private payers and government ( 18 ) . Treatment cost may , therefore , become the primary barrier to HCV eradication ( 19 , 20 ) . The manufacturer contends that sofosbuvir-based treatment provides good value ( 21 ) . However , it remains unclear whether and in which patients the improved benefits of new therapies justify the increased cost compared with the oSOC . In addition , the total spending on new drugs required to treat a large number of patients with HCV is not known . Therefore , the objective of our study was to evaluate the cost-effectiveness and budget impact of sofosbuvirledipasvir from a third-party payer 's perspective . Methods We developed a Markov-based , individual-level , state-transition model , MATCH ( Markov-based Analyses of Treatments for Chronic Hepatitis C ) , that simulated the clinical course of patients with HCV who received antiviral treatment .  We used a weekly cycle length to advance time in the model . The structure of the model was based on our previously published and vali date d Markov cohort model ( 22 , 23 ) . Base-Case Population Our base-case population comprised HCV-infected patients in the United States . We defined a total of 120 patient profiles based on patients ' treatment history ( naive or experienced ) , interferon tolerance ( yes or no [ for treatment-naive patients only ] ) , HCV genotype ( 1 , 2 , 3 , or 4 ) , sex ( male or female ) , and METAVIR fibrosis score ( F0 [ no fibrosis ] , F1 [ portal fibrosis without septa ] , F2 [ portal fibrosis with few septa ] , F3 [ numerous septa without fibrosis ] , or F4 [ cirrhosis ] ) ( 24 ) . We also assigned baseline ages according to fibrosis score by using a vali date d simulation model of the HCV disease burden in the United States ( Table 1 of the Supplement ) ( 25 ) . Supplement . Supplementary Material Treatment For each of the 120 patient profiles , we simulated 2 scenarios : treatment using the oSOC and treatment with sofosbuvirledipasvir ( Table 1 ) ( 11 ) . We used efficacy data from the following recent clinical trials of sofosbuvir and ledipasvir in treatment-naive , treatment-experienced , and interferon-intolerant patients : ION-1 ( 26 ) , ION-2 ( 10 ) , ION-3 ( 27 ) , NEUTRINO ( 9 ) , FISSION ( 9 ) , VALENCE ( 28 ) , POSITRON ( 29 ) , FUSION ( 29 ) , and the Egyptian Ancestry study ( 30 ) . We defined treatment in eligibility due to interferon intolerance as presence of 1 or more of the following conditions : bipolar disorder , anemia ( hemoglobin level < 100 g/L ) , pregnancy , or neutropenia ( neutrophil count < 0.750109 cells/L ) ( 31 ) . For efficacy data from comparator groups , we used either the aforementioned clinical trials ( when the study included the oSOC ) or published studies of protease inhibitors and peginterferonribavirin ( 3240 ) . The duration of treatment in our model varied between 8 and 48 weeks depending on treatment group , HCV genotype , and treatment history . We also included the possibility of early treatment discontinuation because of adverse events or clinical futility rules ( for the oSOC only ) . Table 1 . Treatment-Related Variables for Cost-Effectiveness Analysis  of Sofosbuvir-Based Therapies and the oSOC Natural History of HCV Infection  Patients who did not achieve SVR  transitioned into the natural-history phase of the model , which was defined by using Markov health states . Patients could start in one of the Markov states defined on the basis of the degree of liver fibrosis ( F0 to F4 ) ( Appendix Figure 1 ) and could develop decompensated cirrhosis , HCC , or both ; receive a liver transplant ; or die of a liver-related cause . Those who achieved SVR were assumed to transition into normal health status only if they did not have cirrhosis ( stage F4 ) . In patients with cirr 
    Output:
    
In conclusion , the costs of the majority of new treatments for hematologic cancers are too high to be deemed cost-effective in the United States