***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: The coadministration of ribavirin with recombinant interferon alfa-2b ( rIFN-alpha 2b ) compared with rIFN-alpha 2b alone markedly enhanced sustained virologic response rates in relapsed and treatment-naive chronic hepatitis C patients . The potential for ribavirin to likewise exacerbate the adverse events associated with the alpha interferons is review ed . The overall safety and tolerability of combination rIFN-alpha 2b/ribavirin therapy was evaluated in 2,089 patients treated in phase III clinical studies conducted in the United States and internationally .  Serious adverse events were also evaluated on an interim basis in > 25,000 patients --a majority of whom were treated with combination therapy ( open label)--treated worldwide in investigator-initiated studies . Patients in the phase III studies received 3 million International Units rIFN-alpha 2b three times per week by subcutaneous injection plus either ribavirin or placebo orally in divided daily doses of 1,000 or 1,200 mg for patients weighing < or = 75 or > 75 kg , respectively . Adverse event frequency and severity and dose modifications were recorded throughout the 24-week ( relapse ) or 48-week ( naive ) treatment period and 24-week follow-up period . Clinical ly significant adverse events included anemia and depression . There was no evidence that the adverse effects of alpha interferon ( e.g. , fatigue , depression , neutropenia ) were exacerbated by ribavirin .  Severe adverse events were limited due to strict adherence to dose-modification criteria ; approximately 6 % to 9 % of patients discontinued combination therapy because of an adverse event . Clinical ly serious adverse events , dose reductions and discontinuations , and potential mechanisms of toxicity associated with rIFN-alpha 2b and ribavirin are examined OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Objective : To estimate the cost utility of treatment with combination therapy ( ribavirin and interferon α ) for hepatitis C compared with no treatment or monotherapy ( interferon α ) based on UK costs and clinical management . Design : Decision analysis model using a Markov approach to simulate disease progression . Setting : UK secondary care . Participants : Hypothetical cohort of patients with hepatitis C. Main outcome measures : Cost per quality adjusted life year ( QALY ) gained . Results : Discounted cost per QALY for combination therapy over no treatment was £ 3791 . Cost per QALY varied between £ 1646 and £ 9170 according to subgroup , with the lowest ratios being for genotype 2 or 3 , women , those aged less than 40 years , and those with moderate hepatitis .  The discounted cost per QALY of the combination over monotherapy was £ 3485 . Similar findings were shown for subgroups as for the comparison with no treatment . One way sensitivity analysis showed that while drug costs were more important in the analysis than assumptions about disease progression or costs of treating hepatitis C disease , the results were robust to large changes in underlying assumptions . Conclusions : Combination therapy for hepatitis C is a cost effective treatment option and is superior to monotherapy . Considerable uncertainties remain over the appropriate management strategies in the population s excluded from r and omised controlled trials and in whom treatment is currently being considered in the UK Compared to either drug alone , therapy with the combination of ribavirin and interferon-α leads to improved rates of response in patients with chronic hepatitis C. Side effects often m and ate downward dose adjustment or cessation of therapy , and the optimal dose of ribavirin has not been established . The aim of this study was to learn whether 600 mg ribavirin per day would prove as efficacious as 1000–1200 mg/day when combined with interferon ( 3 million units thrice weekly ) for therapy of patients previously treated with st and ard interferon who had failed to respond or who had relapsed . We enrolled 69 patients with chronic hepatitis C and compensated liver disease : 45 were men , 65 were Caucasian , 48 were infected with genotype 1 hepatitis C virus . By r and om assignment , 35 received 600 mg ribavirin/day ( group A ) , whereas the other 34 received 1000 mg ( ≤75 kg body wt ) or 1200 mg/day ( > 75 kg body wt ) ( group B ) . At baseline , the two groups were well matched for demographic and laboratory features . In both groups , mean serum levels of alanine aminotransferase ( ALT ) and hepatitis C viral ( HCV ) RNA levels fell promptly and remained significantly lower than baseline throughout 24 weeks of therapy . There was no significant difference in mean levels of ALT or HCV RNA during therapy or at the end of follow-up ( 24 weeks after cessation of therapy ) . At the end of 24 weeks of posttherapy follow-up , 12 patients in each group had undetectable HCV RNA in serum , whereas 11 ( 31 % ) in group A and 9 ( 26.5 % ) in group B had normal serum ALT levels . The lower doses of ribavirin ( group A ) were tolerated better . % In conclusion , in previous nonresponders or relapsers to interferon done , combination therapy with interferon-α2b ( 3 MU thrice weekly ) + 600 mg ribavirin/day is tolerated better and is as effective as interferon plus higher ( st and ard ) doses of ribavirin ( 1000–1200 mg/day ) 
    Output:
    
Combination therapy significantly increased the risk of haematological , dermatological , gastrointestinal , infectious , and miscellaneous ( cough , dyspnoea , fatigue ) adverse reactions .
Accordingly , combination therapy significantly increased the risk of treatment discontinuation and dose reductions .
AUTHORS ' CONCLUSIONS Compared with interferon alone , ribavirin plus interferon is more effective in clearing hepatitis C virus from the blood .
The number needed to treat to obtain a beneficial effect is considerable considering the increased risk of several severe adverse reactions and costs