***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: Anemia , one of the most common complications of cancer chemotherapy , has been managed with red blood cell ( RBC ) transfusions . As an alternative , the agent epoetin alfa has the potential to reduce the transfusion requirements of patients receiving cancer chemotherapy . To estimate the value that cancer patients place on the drug , an economic analysis using the concept of willingness to pay ( WTP ) was conducted ABSTRACT Objective : To compare the cost-effectiveness of epoetin alfa ( EPO ) and darbepoetin alfa ( DARB ) for the treatment of chemotherapy-induced anemia ( CIA ) , using dosing regimens approved by the FDA ( EPO 40 000 U once weekly and DARB 2.25 mcg/kg once weekly ) . Methods : The study compared published results of two double-blind , r and omized , phase III trials one utilizing EPO ( N = 166 ) and the other , DARB ( N = 367 ) . Patients in both trials had similar baseline characteristics .  Effectiveness was measured as the proportion of  EPO or DARB  patients who were successfully treated ( i.e. , did not require blood transfusion ) during weeks 0–16 and 5–16 , respectively . Estimated drug costs were presented in 2005 USD based on wholesale acquisition cost ( WAC ) and average drug utilization over 16 weeks . Cost-effectiveness was calculated as the estimated drug costs divided by transfusion effectiveness . Threshold analysis was used to determine the break-even point at which EPO and DARB had the same drug costs . Results : Estimated drug costs over 16 weeks were $ 9039 for EPO and $ 13 555 for DARB . During weeks 5–16 , 85 % of EPO patients and 73 % of DARB patients were successfully treated , result ing in average cost-effectiveness ratios of $ 106 for EPO and $ 186 for DARB per one per cent of successfully treated patients . A 33 % reduction in DARB WAC was required to achieve the same drug costs as for EPO . Conclusions : Utilizing FDA -approved doses , EPO was found to result in lower drug costs and better treatment success when compared to DARB . Hence , EPO is a dominant alternative compared to DARB for the treatment of CIA . The analyses presented here are not without limitations . Specifically , although the studies were comparable , patients were ultimately drawn from different population Previous phase I-II clinical trials have shown that recombinant human erythropoietin ( rHuEpo ) can ameliorate anemia in a portion of patients with multiple myeloma ( MM ) and non-Hodgkin 's lymphoma ( NHL ) . Therefore , we performed a r and omized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo .  A total of 146 patients who had hemoglobin ( Hb ) levels < or = 11 g/dL and who had no need for transfusion at the time of enrollment entered this trial . Patients were r and omized to receive 1,000 U ( n = 31 ) , 2,000 U ( n = 29 ) , 5,000 U ( n = 31 ) , or 10,000 U ( n = 26 ) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy ( n = 29 ) . Of the patients , 84 suffered from MM and 62 from low- to intermediate- grade NHL , including chronic lymphocytic leukemia ; 116 of 146 ( 79 % ) received chemotherapy during the study . The mean baseline Hb level was 9.4 + /- 1.0 g/dL. The median serum Epo level was 32 mU/mL , and endogenous Epo production was found to be defective in 77 % of the patients , as judged by a value for the ratio of observed-to-predicted serum Epo levels ( O/P ratio ) of < or = 0.9 . An intention-to-treat analysis was performed to evaluate treatment efficacy . The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 ( P = .57 ) , 0.22 ( P = .05 ) , 0.43 ( P = .01 ) , and 0.58 ( P = .0001 ) g/dL in the 1,000 U , 2,000 U , 5,000 U , and 10,000 U groups , respectively ( P values versus control ) . The probability of response ( delta Hb > or = 2 g/dL ) increased steadily and , after 8 weeks , reached 31 % ( 2,000 U ) , 61 % ( 5,000 U ) , and 62 % ( 10,000 U ) , respectively . Regression analysis using Cox 's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo , whereas only one quarter of those with adequate Epo levels did so . Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50 % of these patients are expected to respond to rHuEpo . Thus , rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production . From a practical point of view , we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels , whereas the choice of the initial dosage should be based on residual marrow function OBJECTIVE To compare the steady-state pharmacokinetics and pharmacodynamics following multiple subcutaneous administration of a new erythropoiesis stimulating agent ( HX575 , Binocrit , S and oz GmbH , Holzkirchen , Germany ) with that of epoetin beta ( NeoRecormon , Roche Ltd. , Welwyn Garden City , UK ) . METHODS An open , r and omized , parallel group study was conducted in 80 healthy adult males . Subjects were r and omized to multiple subcutaneous doses of 100 IU/kg body weight of HX575 or epoetin beta three-times-weekly for 4 weeks . Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay ( ELISA ) and pharmacokinetic parameters for the two treatments were compared . The time course and area under the effect curve ratios of hematological characteristics were used as surrogate parameters for efficacy evaluation . RESULTS The pharmacokinetic profiles after multiple doses were similar for both treatments . HX575 was bioequivalent to epoetin beta with respect to the rate and extent of exposure of exogenous epoetin , as indicated by the ratios ( 90 % confidence intervals ) of AUC(tau ) ( 96.1 ( 86.4 - 106.9 ) ) and C(max , ss ) ( 98.5 ( 85.2 - 113.9 ) ) . The hematological profiles of both treatments were similar as determined from the population mean curves and the AUEC(Hb ) ratio ( 90 % confidence interval ] ( 99.2 ( 97.7 - 100.7 ) ) , the primary endpoint of this study . Study medication was well tolerated with no clinical ly relevant differences between safety profiles of the treatments . Anti-epoetin antibodies were not detected at any time . CONCLUSIONS HX575 and epoetin beta were bioequivalent with respect to their steady-state pharmacokinetic profile and pharmacodynamic action . These results support the conclusion that HX575 and epoetin beta will be equally efficacious and may be interchangeable as therapy Patients with breast cancer treated with adjuvant chemotherapy  experience not only fatigue and menopausal symptoms but also documented cognitive dysfunction and reduced capacity to carry out activities of daily living . The role of epoetin alfa in improving cognition and functional capacity was assessed in a large r and omized trial through patient self-reported outcomes . Patients with breast cancer ( N = 354 , adjuvant and metastatic ) undergoing chemotherapy  were r and omized in a 1:1 ratio to receive epoetin alfa ( 40,000 IU once weekly ) or the st and ard of care ( SOC ) . Change in patient-reported Health Utilities Index Mark 3 ( HUI3 ) from baseline to week 12 was compared between the epoetin alfa and SOC groups . In addition , correlations between the disease-nonspecific HUI3 utility scale and the cancer-specific quality of life instrument Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) and Fatigue subscales were assessed . Epoetin alfa treatment significantly improved HUI3 scores compared with patients receiving SOC ( P = 0.036 ) . Three subscales within HUI3 were also significantly better for epoetin alfa-treated patients ( emotion , P = 0.048 ; ambulation , P = 0.048 ; and cognition , P = 0.02 ) . Moreover , a strong correlation ( P = 0.0001 ) exists between the disease-nonspecific utility scale HUI3 and the disease-specific FACT-An and FACT-Fatigue scales in terms of overall scores and score changes . The findings of the study demonstrate for the first time in patients with breast cancer that epoetin alfa significantly enhances functional well-being , which translates into significantly better utility scores . In addition , epoetin alfa also significantly improved cognitive function of women undergoing chemotherapy , and this could have an important impact on their lives from a societal perspective Health-related quality of life ( HrQOL ) assessment s are gaining importance as outcome measures in cancer clinical trials . A recently published clinical trial reported statistically significant ( P<0.001 ) increases in haemoglobin ( Hb ) levels and significantly ( P<0.01 ) increased HrQOL scores following the administration of recombinant human erythropoietin ( r-HuEPO , epoetin alfa ) versus placebo to anaemic cancer patients who received non-platinum chemotherapy . This study employed five cancer-specific HrQOL instruments . Hb and HrQOL data from this trial were analysed to estimate the minimally important difference ( MID ) in HrQOL measures that could be interpreted as clinical ly meaningful , with Hb level selected as the best external st and ard . Patients were assigned to two groups : improved ( Hb increases of > /=1 g/dL ) or stable ( change in Hb of-1 g/dL to < 1 g/dL ) . The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group . By this analysis , the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinical ly important for all Hb-sensitive , cancer-specific HrQOL evaluations . Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinical ly significant . These analyses were repeated using a data set from a separate clinical trial , which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre , double-blind study were clinical ly important . These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials Background HX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway . Therefore , in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa , the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations . Methods An open , r and omised , parallel group study was conducted in 80 healthy adult males . Subjects were r and omised to multiple intravenous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa three-times-weekly for four weeks . Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay and pharmacokinetic parameters for the two treatments were compared . The time course and area under the effect curve ratio of haematological characteristics were used as surrogate parameters for efficacy evaluation . Results The haematological profiles of both treatments were similar , as determined from their population mean curves and the AUECHb ratio and 90 % confidence interval ( 99.9 % [ 98.5–101.2 % ] ) , the primary pharmacodynamic endpoint of this study . The pharmacokinetic parameters after the treatments showed minor differences after single dosing , but not at steady state doses . After multiple doses , HX575 was bioequivalent to the comparator with respect to the rate and extent of exposure of exogenous epoetin ( AUCτ ratio and 90 % confidence interval : 89.2 % [ 82.5–96.2 % ] ) . Study medication was well tolerated with no clinical ly relevant differences between safety profiles of the treatments . Anti-epoetin antibodies were not detected . Conclusion HX575 and the comparator epoetin alfa were bioequivalent at steady state circulating drug concentrations with respect to their pharmacokinetic profile and pharmacodynamic action . This supports the conclusion that HX575 and the comparator epoetin alfa , when administered intraveneously , will be equally efficacious and may be interchangeable as therapy PURPOSE Erythropoietin , an oxygen-regulated 
    Output:
    
The results suggest a clinical benefit from ESAs  for anaemia-related outcomes and an improvement in HRQoL scores .
The impact of ESAs on AEs and survival remains highly uncertain , although point estimates are lower , confidence intervals are wide and not statistically significant .
Base-case incremental cost-effectiveness ratios ( ICERs )  for ESA treatment compared with no ESA treatment ranged from £ 19,429 to £ 35,018 per QALY gained , but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs , including the possibility of overall health disbenefit .
ESAs could be cost-effective when used closer to licence , but there is considerable uncertainty , mainly because of unknown impacts on overall survival .