***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 Background Adding abiraterone acetate with prednisolone ( AAP ) or docetaxel with prednisolone ( DocP ) to st and ard-of-care ( SOC ) each improved survival in systemic therapy for advanced or metastatic prostate cancer : evaluation of drug efficacy : a multi-arm multi-stage platform r and omised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term and rogen deprivation therapy ( ADT ) . The protocol provides the only direct , r and omised comparative data of SOC + AAP versus SOC + DocP. Method Recruitment to SOC + DocP  and SOC + AAP overlapped November 2011 to March 2013 . SOC was long-term ADT or , for most non-metastatic cases , ADT for ≥2 years and RT to the primary tumour . Stratified r and omisation allocated pts 2 : 1 : 2 to SOC ; SOC + docetaxel 75 mg/m2 3-weekly × 6 + prednisolone 10 mg daily ; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily . AAP duration depended on stage and intent to give radical RT . The primary outcome measure was death from any cause . Analyses used Cox proportional hazards and flexible parametric models , adjusted for stratification factors . This was not a formally powered comparison . A hazard ratio ( HR ) < 1 favours SOC + AAP , and HR > 1 favours SOC + DocP. Results A total of 566 consenting patients were contemporaneously r and omised : 189 SOC + DocP and 377 SOC + AAP . The patients , balanced by allocated treatment were : 342 ( 60 % ) M1 ; 429 ( 76 % ) Gleason 8–10 ; 449 ( 79 % ) WHO performance status 0 ; median age 66 years and median PSA 56 ng/ml . With median follow-up 4 years , 149 deaths were reported . For overall survival , HR = 1.16 ( 95 % CI 0.82–1.65 ) ; failure-free survival HR = 0.51 ( 95 % CI 0.39–0.67 ) ; progression-free survival HR = 0.65 ( 95 % CI 0.48–0.88 ) ; metastasis-free survival HR = 0.77 ( 95 % CI 0.57–1.03 ) ; prostate cancer-specific survival HR = 1.02 ( 0.70–1.49 ) ; and symptomatic skeletal events HR = 0.83 ( 95 % CI 0.55–1.25 ) . In the safety population , the proportion reporting ≥1 grade 3 , 4 or 5 adverse events ever was 36 % , 13 % and 1 % SOC + DocP , and 40 % , 7 % and 1 % SOC + AAP ; prevalence 11 % at 1 and 2 years on both arms . Relapse treatment patterns varied by arm . Conclusions This direct , r and omised comparative analysis of two new treatment st and ards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival , nor in other important outcomes such as symptomatic skeletal events . Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs . Trial registration Clinical trials.gov : NCT00268476 Purpose Systemic Therapy for Advanced or Metastatic Prostate Cancer : Evaluation of Drug Efficacy is a r and omized controlled trial using a multiarm , multistage , platform design . It recruits men with high-risk , locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy . We report survival data for two celecoxib (Cel)-containing comparisons , which stopped accrual early at interim analysis on the basis of failure-free survival . Patients and Methods St and ard of care ( SOC ) was hormone therapy continuously ( metastatic ) or for ≥ 2 years ( nonmetastatic ) ; prostate ( ± pelvic node ) radiotherapy was encouraged for men without metastases . Cel 400 mg was administered twice a day for 1 year . Zoledronic acid ( ZA ) 4 mg was administered for six 3-weekly cycles , then 4-weekly for 2 years . Stratified r and om assignment allocated patients 2:1:1 to SOC ( control ) , SOC + Cel , or SOC + ZA + Cel . The primary outcome measure was all-cause mortality . Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors . Results A total of 1,245 men were r and omly assigned ( Oct 2005 to April 2011 ) . Groups were balanced : median age , 65 years ; 61 % metastatic , 14 % N+/X M0 , 25 % N0M0 ; 94 % newly diagnosed ; median prostate-specific antigen , 66 ng/mL. Median follow-up was 69 months . Grade 3 to 5 adverse events were seen in 36 % SOC-only , 33 % SOC + Cel , and 32 % SOC + ZA + Cel patients . There were 303 control arm deaths ( 83 % prostate cancer ) , and median survival was 66 months . Compared with SOC , the adjusted hazard ratio was 0.98 ( 95 % CI , 0.80 to 1.20 ; P = .847 ; median survival , 70 months ) for SOC + Cel and 0.86 ( 95 % CI , 0.70 to 1.05 ; P = .130 ; median survival , 76 months ) for SOC + ZA + Cel . Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 ( 95 % CI , 0.62 to 0.98 ; P = .033 ) for SOC + ZA + Cel . Conclusion These data show no overall evidence of improved survival  with Cel . Preplanned subgroup analyses provide hypotheses for future studies 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 Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy .  We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy  , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing  long-term hormone  therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research Objective To evaluate the reliability of risk of bias assessment s based on published trial reports , for determining trial inclusion in meta-analyses . Design Reliability evaluation of risk of bias assessment s. Data sources 13 published individual participant data ( IPD ) meta-analyses in cancer were used to source 95 r and omised controlled trials . Review methods Risk of bias was assessed using the Cochrane risk of bias tool ( RevMan5.1 ) and accompanying guidance . Assessment s were made for individual risk of bias domains and overall for each trial , using information from either trial reports alone or trial reports with additional information collected for IPD meta-analyses . Percentage agreements were calculated for individual domains and overall ( < 66%=low , ≥66%=fair , ≥90%=good ) . The two approaches were considered similarly reliable only when agreement was good . Results Percentage agreement between the two methods for sequence generation and incomplete outcome data was fair ( 69.5 % ( 95 % confidence interval 60.2 % to 78.7 % ) and 80.0 % ( 72.0 % to 88.0 % ) , respectively ) . However , percentage agreement was low for allocation concealment , selective outcome reporting , and overall risk of bias ( 48.4 % ( 38.4 % to 58.5 % ) , 42.1 % ( 32.2 % to 52.0 % ) , and 54.7 % ( 44.7 % to 64.7 % ) , respectively ) . Supplementary information reduced the proportion of unclear assessment s for all individual domains , consequently increasing the number of trials assessed as low risk of bias ( and therefore available for inclusion in meta-analyses ) from 23 ( 23 % ) based on publications alone to 66 ( 66 % ) based on publications with additional information . Conclusions Using cancer trial publications alone to assess risk of bias could be unreliable ; thus , review ers should be cautious about using them as a basis for trial inclusion , particularly for those trials assessed as unclear risk . Supplementary information from trialists should be sought to enable appropriate assessment s and potentially reduce or overcome some risks of bias . Furthermore , guidance should ensure clarity on what constitutes risk of bias , particularly for the more subjective domains Background The multi-arm multi-stage ( MAMS ) trial is a new paradigm for conducting r and omised controlled trials that allows the simultaneous assessment of a number of research treatments against a single control arm . MAMS trials provide earlier answers and are potentially more cost-effective than a series of traditionally design ed trials . Prostate 
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Trial evidence also suggests a benefit of combining celecoxib ( Cel ) with ZA and ADT .
Our results support the use of AAP or Doc with ADT in men with metastatic hormone-naive prostate cancer .
AAP appears to be the most effective treatment , but it is not clear to what extent and whether this is due to a true increased benefit with AAP or the variable features of the individual trials .