***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: BACKGROUND The long-term ( 5 year ) efficacy and safety of tacrolimus ( FK506 ) and cyclosporine were compared in primary liver transplant recipients who participated in a 1-year r and omized , multicenter trial and a 4-year follow-up extension study . METHODS A total of 529 patients ( 263 tacrolimus group , 266 cyclosporine group ) were r and omized to study drug . Patients were evaluated at 3-month intervals . Patient and graft survival rates , incidence of adverse events , and changes in laboratory and clinical profiles were determined . RESULTS Cumulative 5-year patient and graft survival rates were comparable for the tacrolimus ( 79.0 % , 71.8 % ) and cyclosporine ( 73.1 % , 66.4 % ) groups . However , patient half-life survival was longer for tacrolimus-treated patients ( 25.1+/-5.1 years versus 15.2+/-2.5 years ; P=0.049 ) . Improved patient survival with tacrolimus was also observed for hepatitis C-positive patients ( 78.9 % tacrolimus group versus 60.5 % cyclosporine group ; P=0.041 ) . Both treatments were associated with a low incidence of late acute rejection , late steroid-resistant rejection , and death or graft loss related to rejection . Both treatments demonstrated an acceptable safety profile with maintenance of adequate renal and liver function and a low incidence of malignancy/lymphoproliferative disease and serious infections . CONCLUSIONS Tacrolimus is a safe and effective long-term maintenance immunosuppressive agent in primary liver transplantation Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Informing health care decision making may necessitate the synthesis of evidence from different study design s ( e.g. , r and omised controlled trials , non-r and omised/observational studies ) . Methods for synthesis ing different types of studies have been proposed , but their routine use requires development of approaches to adjust for potential biases , especially among non-r and omised studies . The objective of this study was to extend a published Bayesian hierarchical model to adjust for bias due to confounding in synthesis ing evidence from studies with different design s. Methods In this new method ological approach , study estimates were adjusted for potential confounders using differences in patient characteristics ( e.g. , age ) between study arms . The new model was applied to synthesis e evidence from r and omised and  non-r  and omised studies from a published review comparing treatments for abdominal aortic aneurysms . We compared the results of the Bayesian hierarchical model adjusted for differences in study arms with : 1 ) unadjusted results , 2 ) results adjusted using aggregate study values and 3 ) two methods for downweighting the potentially biased non-r and omised studies . Sensitivity of the results to alternative prior distributions and the inclusion of additional covariates were also assessed . Results In the base case analysis , the estimated odds ratio was 0.32 ( 0.13,0.76 ) for the r and omised studies alone and 0.57 ( 0.41,0.82 ) for the non-r and omised studies alone . The unadjusted result for the two types combined was 0.49 ( 0.21,0.98 ) . Adjusted for differences between study arms , the estimated odds ratio was 0.37 ( 0.17,0.77 ) , representing a shift towards the estimate for the r and omised studies alone . Adjustment for aggregate values result ed in an estimate of 0.60 ( 0.28,1.20 ) . The two methods used for downweighting gave odd ratios of 0.43 ( 0.18,0.89 ) and 0.35 ( 0.16,0.76 ) , respectively . Point estimates were robust but credible intervals were wider when using vaguer priors . Conclusions Covariate adjustment using aggregate study values does not account for covariate imbalances between treatment arms and downweighting may not eliminate bias . Adjustment using differences in patient characteristics between arms provides a systematic way of adjusting for bias due to confounding . Within the context of a Bayesian hierarchical model , such an approach could facilitate the use of all available evidence to inform health policy decisions OBJECTIVES Health decision-makers involved with coverage and payment policies are increasingly developing policies that seek information on " real-world " ( RW ) outcomes . Motivated by these initiatives , the International Society for Pharmacoeconomics and Outcomes Research ( ISPOR ) created a Task Force on Real-World Data to develop a framework to assist health-care decision-makers in dealing with RW data , especially related to coverage and payment decisions . METHODS Task Force cochairs were selected by the ISPOR Board of Directors . Cochairs selected chairs for four working groups on : clinical outcomes , economic outcomes , patient-reported outcomes , and evidence hierarchies . Task Force members included representatives from academia , the pharmaceutical industry , and health insurers . The Task Force met on several occasions , conducted frequent correspondence and exchanges of drafts , and solicited comments on three drafts from a core group of external review ers and from the ISPOR membership . RESULTS We defined RW data as data used for decision-making that are not collected in conventional r and omized controlled trials ( RCTs ) . We considered several characterizations : by type of outcome ( clinical , economic , and patient-reported ) , by hierarchies of evidence ( which rank evidence according to the strength of research design ) , and by type of data source ( supplementary data collection alongside RCTs , large simple trials , patient registries , administrative cl aims data base , surveys , and medical records ) . Our report discusses eight key issues : 1 ) the importance of RW data ; 2 ) limitations of RW data ; 3 ) the fact that the level of evidence required depends on the circumstance ; 4 ) the need for good research practice s for collecting and reporting RW data ; 5 ) the need for good process in using RW data in coverage and reimbursement decisions ; 6 ) the need to consider costs and benefits of data collection ; 7 ) the ongoing need for modeling ; and 8) the need for continued stakeholder dialogue on these topics . CONCLUSIONS Real-world data are essential for sound coverage and reimbursement decisions . The types and applications of such data are varied , and context matters greatly in determining the value of a particular type in any circumstance . It is critical that policymakers recognize the benefits , limitations , and method ological challenges in using RW data , and the need to consider carefully the costs and benefits of different forms of data collection in different situations CONTEXT Controversy and uncertainty ensue when the results of clinical research on the effectiveness of interventions are subsequently contradicted . Controversies are most prominent when high-impact research is involved . OBJECTIVES To underst and how frequently highly cited studies are contradicted or find effects that are stronger than in other similar studies and to discern whether specific characteristics are associated with such refutation over time . DESIGN All original clinical research studies published in 3 major general clinical journals or high-impact-factor specialty journals in 1990 - 2003 and cited more than 1000 times in the literature were examined . MAIN OUTCOME MEASURE The results of highly cited articles were compared against subsequent studies of comparable or larger sample size and similar or better controlled design s. The same analysis was also performed comparatively for matched studies that were not so highly cited . RESULTS Of 49 highly cited original clinical research studies , 45 cl aim ed that the intervention was effective .  Of these , 7 ( 16 % ) were contradicted by subsequent studies , 7 others ( 16 % ) had found effects that were stronger than those of subsequent studies , 20 ( 44 % ) were replicated , and 11 ( 24 % ) remained largely unchallenged . Five of 6 highly-cited nonr and omized studies had been contradicted or had found stronger effects vs 9 of 39 r and omized controlled trials ( P = .008 ) . Among r and omized trials , studies with contradicted or stronger effects were smaller ( P = .009 ) than replicated or unchallenged studies although there was no statistically significant difference in their early or overall citation impact . Matched control studies did not have a significantly different share of refuted results than highly cited studies , but they included more studies with " negative " results . CONCLUSIONS Contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes . The extent to which high citations may provoke contradictions and vice versa needs more study . Controversies are most common with highly cited nonr and omized studies , but even the most highly cited r and omized trials may be challenged and refuted over time , especially small ones The LIS2 T study was an open-label , multicenter study in which recipients of a primary liver transplant were r and omized to cyclosporine microemulsion ( CsA-ME ) ( Neoral ) ( n = 250 ) ( monitoring of blood concentration at 2 hours postdose ) C2 or tacrolimus ( n = 245 ) ( monitoring of trough drug blood level [ predose ] ) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months . All patients received steroids with or without azathioprine . At 12 months , 85 % of CsA-ME patients and 86 % of tacrolimus patients survived with a functioning graft ( P not significant ) . Efficacy was similar in deceased- and living-donor recipients . Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME ( 5/88 , 6 % ) than with tacrolimus ( 14/85 , 16 % ) ( P < 0.03 ) . Recurrence of hepatitis C virus in liver grafts was similar in each group . Based on biopsies driven by clinical events , the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME ( 100 + /- 50 days ) than with tacrolimus ( 70 + /- 40 days ) ( P < 0.05 ) . Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus . More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months ( 13 % vs. 5 % , P < 0.01 ) . Of patients who were diabetic at baseline , more tacrolimus-treated individuals required anti-diabetic treatment at 12 months ( 70 % vs. 49 % , P = 0.02 ) . Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups . In conclusion , the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months , and renal function is similar . More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline REFINE was a 12‐month , prospect i ve , open‐label study in 356 patients receiving de novo liver transplantation for hepatitis C virus ( HCV ) cirrhosis , r and omized to  cyclosporine A ( CsA ) or tacrolimus with ( i ) no steroids , IL‐2 receptor antibody induction and mycophenolic acid , or ( ii ) slow steroid tapering . The primary analysis population based on availability of liver biopsies comprised 165 patients ( 88 CsA , 77 tacrolimus ) . There was no difference in the primary endpoint , fibrosis stage ≥2 at 12 months , which occurred in 63/88 CsA‐treated patients ( 71.6 % ) and 52/77 tacrolimus‐treated patients ( 67.5 % ) ( odds ratio [ OR ] 1.11 ; 95 % CI 0.56 , 2.21 ; p = 0.759 ) . Similarly , no significant between‐group difference occurred at month 24 ( OR 1.15 ; 95 % CI 0.47 , 2.80 ; p = 0.767 ) . Among steroid‐free  patients , fibrosis score ≥2 was significantly less frequent with CsA versus tacrolimus at month 12 ( 7/37 [ 18.9 % ] vs. 16/38 [ 42.1 % ] ; p = 0.029 ) . HCV viral load was similar in both the tacrolimus‐ and CsA‐treated cohorts . Mean blood glucose was significantly higher with tacrolimus from day 15 onward . Biopsy‐proven acute rejection , graft loss and death were similar . These results showed no differences in posttransplant HCV‐induced liver fibrosis between patients treated with CsA or tacrolimus in steroid‐containing regimens , whereas CsA in steroid‐free protocol s was associated with reduced severity of fibrosis progression at 1 year posttransplant Background With effective agents available to prevent posttransplantation acute organ rejection , medication adherence becomes a key factor for successful treatment outcomes after renal transplantation . A once-daily , modified-release oral formulation of tacrolimus has been developed to simplify dosing and improve medication adherence . Methods Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograft to Advagraf is a r and omized multicenter controlled trial to evaluate adherence between a tacrolimus once-daily regimen and a tacrolimus twice-daily regimen using an electronic monitor to document drug intake 
    Output:
    
There were no significant differences between ciclosporin and tacrolimus in terms of graft loss or AR .
CONCLUSIONS Meta- analysis of RCTs published since 2000 showed tacrolimus to be superior to ciclosporin in terms of patient mortality and hypertension , while ciclosporin was superior in terms of NODAT .
No significant differences were identified in terms of graft loss or AR .
These findings provide further evidence supporting the use of tacrolimus as the cornerstone of immunosuppressive therapy in liver transplant recipients