***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: Objective To assess the incremental cost and cost-effectiveness of continuous and discontinuous regimens of bevacizumab ( Avastin ) and ranibizumab ( Lucentis ) for neovascular age-related macular degeneration ( nAMD ) from a UK National Health Service ( NHS ) perspective . Design A within-trial cost-utility analysis with a 2-year time horizon , based on a multicentre factorial , non-inferiority r and omised controlled trial . Setting 23 hospital ophthalmology clinics . Participants 610 patients aged ≥50 years with untreated nAMD in the study eye . Interventions 0.5 mg ranibizumab or 1.25 mg bevacizumab given continuously ( monthly ) or discontinuously ( as-needed ) for 2 years . Main outcome measures Quality -adjusted life-years ( QALYs ) . Results Total 2-year costs ranged from £ 3002/patient ( $ 4700 ; 95 % CI £ 2601 to £ 3403 ) for discontinuous bevacizumab to £ 18 590/patient ( $ 29 106 ; 95 % CI £ 18 258 to £ 18 922 ) for continuous ranibizumab . Ranibizumab was significantly more costly  than bevacizumab for both continuous ( + £ 14 989/patient ( $ 23 468 ) ; 95 % CI £ 14 522 to £ 15 456 ; p<0.001 ) and discontinuous treatment ( + £ 8498 ( $ 13 305 ) ; 95 % CI £ 7700 to £ 9295 ; p<0.001 ) , with negligible difference in QALYs . Continuous ranibizumab would only be cost-effective compared with continuous bevacizumab if the NHS were willing to pay £ 3.5 million ( $ 5.5 million ) per additional QALY gained . Patients receiving continuous bevacizumab  accrued higher total costs ( + £ 599 ( $ 938 ) ; 95 % CI £ 91 to £ 1107 ; p=0.021 ) than those receiving discontinuous bevacizumab , but also accrued non-significantly more QALYs ( + 0.020 ; 95 % CI −0.032 to 0.071 ; p=0.452 ) . Continuous bevacizumab therefore cost £ 30 220 ( $ 47 316 ) per QALY gained versus discontinuous bevacizumab . However , bootstrapping demonstrated that if the NHS is willing to pay £ 20 000/QALY gained , there is a 37 % chance that continuous bevacizumab  is cost-effective versus discontinuous bevacizumab . Conclusions Ranibizumab  is not cost-effective compared with bevacizumab , being substantially more costly and producing little or no QALY gain . Discontinuous bevacizumab is likely to be the most cost-effective of the four treatment strategies evaluated in this UK trial , although there is a 37 % chance that continuous bevacizumab is cost-effective . Trial registration number IS RCT N92166560 BACKGROUND Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration . The Inhibition of VEGF in Age-related choroidal Neovascularisation ( IVAN ) trial was design ed to compare these drugs and different regimens . Here , we report the findings at the prespecified 2-year timepoint . METHODS In a multicentre , 2 × 2 factorial , non-inferiority r and omised trial , we enrolled adults aged at least 50 years with active , previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity ( BCVA ) of at least 25 letters from 23 hospitals in the UK . Participants were r and omly assigned ( 1:1:1:1 ) to intravitreal injections of ranibizumab ( 0·5 mg ) or bevacizumab ( 1·25 mg ) in continuous ( every month ) or discontinuous ( as needed ) regimens , with monthly review . Study participants and clinical assessors were masked to drug allocation . Allocation to continuous or discontinuous treatment was masked up to 3 months , at which point investigators and participants were unmasked . The primary outcome was BCVA at 2 years , with a prespecified non-inferiority limit of 3·5 letters . The primary safety outcome was arterial thrombotic event or hospital admission for heart failure . Analyses were by modified intention to treat . This trial is registered , number IS RCT N92166560 . FINDINGS Between March 27 , 2008 , and Oct 15 , 2010 , 628 patients underwent r and omisation . 18 were withdrawn ; 610 received study drugs ( 314 ranibizumab ; 296 bevacizumab ) and were included in analyses . 525 participants reached the visit at 2 years : 134 ranibizumab in continuous regimen , 137 ranibizumab in discontinuous regimen , 127 bevacizumab in continuous regimen , and 127 bevacizumab in discontinuous regimen . For BCVA , bevacizumab was neither non-inferior nor inferior to ranibizumab ( mean difference -1·37 letters , 95 % CI -3·75 to 1·01 ; p=0·26 ) . Discontinuous treatment was neither non-inferior nor inferior to continuous treatment ( -1·63 letters , -4·01 to 0·75 ; p=0·18 ) . Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab ( 20 [ 6 % ] of 314 participants ) and bevacizumab ( 12 [ 4 % ] of 296 ; odds ratio [ OR ] 1·69 , 95 % CI 0·80 - 3·57 ; p=0·16 ) , or those given continuous ( 12 [ 4 % ] of 308 ) and discontinuous treatment ( 20 [ 7 % ] of 302 ; 0·56 , 0·27 - 1·19 ; p=0·13 ) . Mortality was lower with continuous than discontinuous treatment ( OR 0·47 , 95 % CI 0·22 - 1·03 ; p=0·05 ) , but did not differ by drug group ( 0·96 , 0·46 - 2·02 ; p=0·91 ) . INTERPRETATION Ranibizumab and bevacizumab have similar efficacy . Reduction in the frequency of retreatment result ed in a small loss of efficacy irrespective of drug . Safety was worse when treatment was administered discontinuously . These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought . FUNDING UK National Institute for Health Research Health Technology Assessment programme Background The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials . For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date . However , if proved non-inferior to ranibizumab , use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity . A cost-effectiveness study has been design ed to substantiate this hypothesis . Aim To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema . It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness . Design This is a r and omized , controlled , double masked , clinical trial in 246 patients in seven academic trial centres in The Netherl and s. Outcomes The primary outcome measure is the change in best-corrected visual acuity ( BCVA ) in the study eye from baseline to month 6 . Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months , the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months , the number of adverse events in 6 months , and the costs per quality adjusted life-year of the two treatments BACKGROUND Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration ( AMD ) . In addition , bevacizumab is used off-label to treat AMD , despite the absence of similar supporting data . METHODS In a multicenter , single-blind , noninferiority trial , we r and omly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation . The primary outcome was the mean change in visual acuity at 1 year , with a noninferiority limit of 5 letters on the eye chart . RESULTS Bevacizumab administered monthly was equivalent to ranibizumab administered monthly , with 8.0 and 8.5 letters gained , respectively . Bevacizumab administered as needed was equivalent to ranibizumab as needed , with 5.9 and 6.8 letters gained , respectively . Ranibizumab as needed was equivalent to monthly ranibizumab , although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive . The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group ( 196 μm ) than in the other groups ( 152 to 168 μm , P=0.03 by analysis of variance ) . Rates of death , myocardial infa rct ion , and stroke were similar for patients receiving either bevacizumab or ranibizumab ( P>0.20 ) . The proportion of patients with serious systemic adverse events ( primarily hospitalizations ) was higher with bevacizumab than with ranibizumab ( 24.1 % vs. 19.0 % ; risk ratio , 1.29 ; 95 % confidence interval , 1.01 to 1.66 ) , with excess events broadly distributed in disease categories not identified in previous studies as areas of concern . CONCLUSIONS At 1 year , bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule . Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly . Differences in rates of serious adverse events require further study . ( Funded by the National Eye Institute ; Clinical Trials.gov number , NCT00593450 . ) PURPOSE To assess long-term outcomes 7 to 8 years after initiation of intensive ranibizumab therapy in exudative age-related macular degeneration ( AMD ) patients . DESIGN Multicenter , noninterventional cohort study . PARTICIPANTS Sixty-five AMD patients originally treated with ranibizumab in the phase 3 Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD ( ANCHOR ) trial , Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD ( MARINA ) trial , and Open-Label Extension Trial of Ranibizumab  for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration ( HORIZON ) . METHODS Fourteen clinical trial sites recruited their original subjects for a return evaluation . Individual subject comparisons were obtained from the ANCHOR , MARINA , and HORIZON data bases . MAIN OUTCOME MEASURES The primary end point was percentage with best-corrected visual acuity ( BCVA ) of 20/70 or better ; secondary outcomes included mean change in letter score compared with previous time points and anatomic results on fluorescein angiography , spectral-domain ocular coherence tomography ( OCT ) , and fundus autofluorescence ( FAF ) . RESULTS At a mean of 7.3 years ( range , 6.3 - 8.5 years ) after entry into ANCHOR or MARINA , 37 % of study eyes met the primary end point of 20/70 or better BCVA , with 23 % achieving a BCVA of 20/40 or better . Thirty-seven percent of study eyes had BCVA of 20/200 or worse . Forty-three percent of study eyes had a stable or improved letter score ( ≥0-letter gain ) compared with ANCHOR or MARINA baseline measurements , whereas 34 % declined by 15 letters or more , with overall a mean decline of 8.6 letters ( P<0.005 ) . Since exit from the HORIZON study , study eyes had received a mean of 6.8 anti-vascular endothelial growth factor ( VEGF ) injections during the mean 3.4-year interval ; a subgroup of patients who received 11 or more anti-VEGF injections had a significantly better mean gain in letter score since HORIZON exit ( P 
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A third drug , bevacizumab ( Avastin ) , is only licensed for colorectal cancer , and therefore , use in the eye is ‘ off label’.1 Yet , all three are effective .