***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 and Purpose — End point adjudication committees ( EPAC ) are widely used in large-scale clinical trials to ensure the robustness of diagnosis for end points . Methods — The Perindopril Protection Against Recurrent Stroke Study ( PROGRESS ) was a double-blind r and omized trial of blood pressure lowering in 6105 participants with pre-existing cerebrovascular disease . Separate estimates of the effects of r and omized treatment were determined using Cox regression models that were based on the unadjudicated events initially reported by the investigator and on the final events assigned by the EPAC . Results — There were 992 strokes initially reported by the investigators and 894 ( 90 % ) retained these diagnoses after adjudication by the EPAC . The hazard ratios ( 95 % CIs ) for the effect of r and omized treatment on stroke were 0.74 ( 0.64 to 0.85 ) based on the investigator diagnoses and 0.72 ( 0.62 to 0.83 ) based on the EPAC diagnoses ( P homogeneity=0.7 ) . For each stroke subtype reported , the corresponding numbers of diagnoses ( investigators/EPAC ) were ischemic ( 593/565 ) , hemorrhagic ( 124/111 ) , and unknown ( 124/93 ) with no impact of the EPAC review on the estimates of treatment effects ( all P homogeneity > 0.3 ) . There was likewise no detectable effect of reclassification of diagnoses for the effect estimates calculated for myocardial infa rct ion or the main causes of death ( all P homogeneity > 0.5 ) . Conclusion — The EPAC process had no discernible impact on the trial conclusions . Very large trials powered to detect effects on stroke subtypes might obtain real scientific gain from an EPAC , but in the case of PROGRESS , the value of the EPAC was in the reassurance it provided Background : TORCH ( Towards a Revolution in COPD Health ) is an international multicentre , r and omised , placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease ( COPD ) . The primary outcome is all-cause mortality . Cause-specific mortality and deaths related to COPD are additional outcome measures , but systematic methods for ascertainment of these outcomes have not previously been described . Methods : A Clinical Endpoint Committee ( CEC ) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic , unbiased and independent manner . The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD -relatedness ; the independent review of cases by all members with development of a consensus opinion ; and a substantial infrastructure to collect medical information . Results : 911 deaths were review ed and consensus was reached in all . Cause-specific mortality was : cardiovascular 27 % , respiratory 35 % , cancer 21 % , other 10 % and unknown 8 % . 40 % of deaths were definitely or probably related to COPD . Adjudications were identical in 83 % of blindly re-adjudicated cases ( κ = 0.80 ) . COPD -relatedness was reproduced 84 % of the time ( κ = 0.73 ) . The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52 % of cases . Conclusion : A CEC can provide st and ardised , reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators CONTEXT Despite many therapeutic advances , mortality in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) remains high . The role of additional antithrombotic agents is unclear , especially among patients not receiving reperfusion therapy . OBJECTIVE To evaluate the effect of fondaparinux , a factor Xa inhibitor , when initiated early and given for up to 8 days vs usual care ( placebo in those in whom unfractionated heparin [ UFH ] is not indicated [ stratum 1 ] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [ stratum 2 ] ) in patients with STEMI . DESIGN , SETTING , AND PARTICIPANTS R and omized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12,092 patients with STEMI from 447 hospitals in 41 countries ( September 2003-January 2006 ) . From day 3 through day 9 , all patients received either fondaparinux or placebo according to the original r and omized assignment . MAIN OUTCOME MEASURES Composite of death or reinfa rct ion at 30 days ( primary ) with secondary assessment s at 9 days and at final follow-up ( 3 or 6 months ) . RESULTS Death or reinfa rct ion at 30 days was significantly reduced from 677 ( 11.2 % ) of 6056 patients in the control group to 585 ( 9.7 % ) of 6036 patients in the fondaparinux group ( hazard ratio [ HR ] , 0.86 ; 95 % confidence interval [ CI ] , 0.77 - 0.96 ; P = .008 ) ; absolute risk reduction , 1.5 % ; 95 % CI , 0.4%-2.6 % ) . These benefits were observed at 9 days ( 537 [ 8.9 % ] placebo vs 444 [ 7.4 % ] fondaparinux ; HR , 0.83 ; 95 % CI , 0.73 - 0.94 ; P = .003 , and at study end ( 857 [ 14.8 % ] placebo vs 756 [ 13.4 % ] fondaparinux ; HR , 0.88 ; 95 % CI , 0.79 - 0.97 ; P = .008 ) . Mortality was significantly reduced throughout the study . There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use . However , there was no benefit in those undergoing primary percutaneous coronary intervention . In other patients in stratum 2 , fondaparinux was superior to unfractionated heparin in preventing death or reinfa rct ion at 30 days ( HR , 0.82 ; 95 % CI , 0.66 - 1.02 ; P = .08 ) and at study end ( HR , 0.77 ; 95 % CI , 0.64 - 0.93 ; P = .008 ) . Significant benefits were observed in those receiving thrombolytic therapy ( HR , 0.79 ; P = .003 ) and those not receiving any reperfusion therapy ( HR , 0.80 ; P = .03 ) . There was a tendency to fewer severe bleeds ( 79 for placebo vs 61 for fondaparinux ; P = .13 ) , with significantly fewer cardiac tamponade ( 48 vs 28 ; P = .02 ) with fondaparinux at 9 days . CONCLUSION In patients with STEMI , particularly those not undergoing primary percutaneous coronary intervention , fondaparinux significantly reduces mortality and reinfa rct ion without increasing bleeding and strokes . TRIAL REGISTRATION Clinical Trials.gov Identifier NCT00064428 INTRODUCTION Several anticoagulants have been associated with a ' rebound effect ' that potentially increases the risk of thrombosis and cardiovascular events following discontinuation . Four Phase 3 trials of dabigatran etexilate in major orthopedic surgery incorporated measures to assess the risk of acute coronary syndrome ( ACS ) events during and after treatment . MATERIAL S AND METHODS Patients in RE-MOBILIZE ® , RE-MODEL ™ , RE-NOVATE ® , and RENOVATE ® II were r and omized  to dabigatran etexilate ( 150 mg or 220 mg once daily ) or enoxaparin for 6 - 35 days , and followed for up to 90 days . ACS data were tabulated from investigator-reported serious adverse events using ACS-specific Medical Dictionary for Regulatory Authorities ( MedDRA ) lower-level terms . To ensure that all ACS events were identified in the initial three studies , RE-MOBILIZE ® , RE-MODEL ™ , and RE-NOVATE ® , a broader list of MedDRA terms was prespecified that would trigger treatment-blinded adjudication . RESULTS When pooling the four trials , patients receiving dabigatran etexilate 220 mg had the fewest treatment-emergent , investigator-reported ACS events ( 6 [ 0.16 % ] vs 14 [ 0.51 % ] for dabigatran 150 mg and 13 [ 0.35 % ] for enoxaparin ) . Corresponding post-treatment rates were 2 ( 0.06 % ) , 1 ( 0.04 % ) , and 4 ( 0.11 % ) . Similarly , treatment-emergent central ly adjudicated definite or likely ACS events in the first three trials were fewer in patients on dabigatran 220 mg ( 16 [ 0.60 % ] ) than dabigatran 150 mg ( 26 [ 0.95 % ] ) and enoxaparin ( 20 [ 0.74 % ] ) . The corresponding numbers post treatment were 2 , 2 , and 7 . None of these between-group differences were statistically significant . CONCLUSION No increased ACS signal was detected with dabigatran etexilate compared with enoxaparin during or after treatment Correctable weaknesses in the design , conduct , and analysis of biomedical and public health research studies can produce misleading results and waste valuable re sources . Small effects can be difficult to distinguish from bias introduced by study design and analyses . An absence of detailed written protocol s and poor documentation of research is common . Information obtained might not be useful or important , and statistical precision or power is often too low or used in a misleading way . Insufficient consideration might be given to both previous and continuing studies . Arbitrary choice of analyses and an overemphasis on r and om extremes might affect the reported findings . Several problems relate to the research workforce , including failure to involve experienced statisticians and method ologists , failure to train clinical research ers and laboratory scientists in research methods and design , and the involvement of stakeholders with conflicts of interest . Inadequate emphasis is placed on recording of research decisions and on reproducibility of research . Finally , reward systems incentivise quantity more than quality , and novelty more than reliability . We propose potential solutions for these problems , including improvements in protocol s and documentation , consideration of evidence from studies in progress , st and ardisation of research efforts , optimisation and training of an experienced and non-conflicted scientific workforce , and reconsideration of scientific reward systems Central adjudication in r and omised controlled outcome -driven trials represents a traditional approach to maintain data integrity by applying uniformed rules for assessment of clinical events . It was the purpose of this investigation to determine the patterns of  myocardial infa rct ion ( MI ) adjudication in the TRITON , RECORD , and PLATO trials . We were matching central ly-adjudicated MI 's ( CAMI 's ) from the official trial publication with the site-reported MI ( SRMI 's ) count from the Food and Drug Administration 's secondary analyses for the investigational compounds prasugrel ( TRITON ) , rosiglitazone ( RECORD ) , and ticagrelor ( PLATO ) . CAMI numbers showed a remarkable discrepancy to SRMI 's by more than a doubling of the difference : from 72 to 145 events in TRITON favoring prasugrel ( from a hazard ratio [HR]=0.76 , p=0.08 ; to a HR=0.76 , p<0.001 ) , and from 44 to 89 events in favour of ticagrelor in PLATO ( from a HR=0.94 , p=0.095 ; to a HR=0.84 , p<0.001 ) . In contrast , in the RECORD trial , the CAMI count was less than the SRMI count ( from 24 to 8 events , from a HR=1.42 , p=0.93 ; to a HR=1.14 , p=0.96 ) , in this case diminishing cardiovascular hazards in favour of rosiglitazone . In conclusion , central adjudication in the TRITON , the RECORD , and the PLATO trial turned out to have a critical impact on study outcomes . Trial publications should in the future include site-reported major efficacy and safety endpoints to preserve data integrity . The regulatory authorities should consider independent audits when there is a major disagreement between central ly adjudicated and site reported events influencing the results of a major clinical trial Background Limited information has been published regarding how specific processes for event adjudication can affect event rates in trials . We review ed nonfatal myocardial infa rct ions ( MIs ) reported by site investigators in the international Platelet Glycoprotein IIb/IIIa in Unstable Angina : Receptor Suppression Using Integrilin ( Eptifibatide ) Therapy ( PURSUIT ) trial and those adjudicated by a central clinical events committee ( CEC ) to determine the reasons for differences in event rates . Methods The PURSUIT trial r and omised 10,948 patients with acute coronary syndromes to receive eptifibatide or placebo .  The primary end-point was death or post- 
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However , there was a statistically significant interaction between these subgroups ( P = 0.03 ) AUTHORS ' CONCLUSIONS : On average , treatment effect estimates for subjective outcome events assessed by onsite assessors did not differ from those assessed by ACs .
Results of subgroup analysis showed an interaction according to the blinded status of onsite assessors and the process used to su bmi t data to AC .
These results suggest that the use of ACs might be most important when onsite assessors are not blinded and the risk of misclassification is high .
Furthermore , research is needed to explore the impact of the different procedures used to select events to adjudicate