***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: Although r and omised trials are important for evidence -based medicine , little is known about their overall characteristics . We assessed the epidemiology and reporting of method ological details for all 519 PubMed -indexed r and omised trials published in December , 2000 ( 383 [ 74 % ] parallel-group , 116 [ 22 % ] crossover ) . 482 ( 93 % ) were published in specialty journals . A median of 80 participants ( 10th-90th percentile 25 - 369 ) were recruited for parallel-group trials . 309 ( 60 % ) were blinded . Power calculation , primary outcomes , r and om sequence generation , allocation concealment , and h and ling of attrition were each adequately described in less than half of publications . The small sample sizes are worrying , and poor reporting of method ological characteristics will prevent reliable quality assessment of many published trials Abstract Objective : To determine the effect of antibiotic treatment for acute otitis media in children between 6 months and 2 years of age . Design : Practice based , double blind , r and omised , placebo controlled trial . Setting : 53 general practice s in the Netherl and s. Subjects : 240 children aged 6 months to 2 years with the diagnosis of acute otitis media . Intervention : Amoxicillin 40 mg/kg/day in three doses . Main outcome measures : Persistent symptoms at day four and duration of fever and pain or crying , or both . Otoscopy at days four and 11 , tympanometry at six weeks , and use of analgesic . Results : Persistent symptoms at day four were less common in the amoxicillin group ( risk difference 13 % ; 95 % confidence interval 1 % to 25 % ) . The median duration of fever was two days in the amoxicillin group versus three in the placebo group ( P=0.004 ) . No significant difference was observed in duration of pain or crying , but analgesic consumption was higher in the placebo group during the first 10 days ( 4.1 v 2.3 doses , P=0.004 ) . In addition , no otoscopic differences were observed at days four and 11 , and tympanometric findings at six weeks were similar in both groups . Conclusions : Seven to eight children aged 6 to 24 months with acute otitis media needed to be treated with antibiotics to improve symptomatic outcome at day four in one child . This modest effect does not justify prescription of antibiotics at the first visit , provided close surveillance can be guaranteed BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion OBJECTIVE --To examine the efficacy and safety of conservative management of mild otitis media ( " the acute red ear " ) in children . DESIGN --Double blind placebo controlled trial . SETTING --17 group general practice s ( 48 general practitioners ) in Southampton , Bristol , and Portsmouth . PATIENTS --232 children aged 3 - 10 years with acute earache and at least one abnormal eardrum ( 114 allocated to receive antibiotic  , 118  placebo ) . INTERVENTIONS --Amoxycillin 125 mg three times a day for seven days or matching placebo ; 100 ml paracetamol 120 mg/5 ml . MAIN OUTCOME MEASURES --Diary records of pain and crying , use of analgesic , eardrum signs , failure of treatment , tympanometry at one and three months , recurrence rate , and ear , nose , and throat referral rate over one year . RESULTS --Treatment failure was eight times more likely in the placebo than the antibiotic group ( 14.4 % v 1.7 % , odds ratio 8.21 , 95 % confidence interval 1.94 to 34.7 ) . Children in the placebo group showed a significantly higher incidence of fever on the day after entry ( 20 % v 8 % , p less than 0.05 ) , mean analgesic consumption ( 0.36 ml/h v 0.21 ml/h , difference 0.14 , 95 % confidence interval 0.07 to 0.23 ; p = 0.0022 ) , mean duration of crying ( 1.44 days v 0.50 days , 0.94 ; 0.50 to 1.38 ; p less than 0.001 ) , and mean absence from school ( 1.96 days v 0.52 days , 1.45 ; 0.46 to 2.42 ; p = 0.0132 ) . Differences in recorded pain were not significant . The prevalence of middle ear effusion at one or three months , as defined by tympanometry , was not significantly different , nor was there any difference in recurrence rate or in ear , nose , and throat referral rate in the follow up year . No characteristics could be identified which predicted an adverse outcome . CONCLUSIONS --Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy R and omised controlled trials ( RCTs ) must be internally valid ( i.e. , design and conduct must eliminate the possibility of bias ) , but to be clinical ly useful , the result must also be relevant to a definable group of patients in a particular clinical setting ( i.e. , they must be externally valid ) . Lack of external validity is the most frequent criticism by clinicians of RCTs , systematic review s , and guidelines , and is one explanation for the widespread underuse in routine practice of many treatments that have been shown to be beneficial in trials and are recommended in guidelines [ 1 ] . Yet medical journals , funding agencies , ethics committees , the pharmaceutical industry , and governmental regulators seem to give external validity a low priority . Admittedly , whereas the determinants of internal validity are intuitive and can generally be worked out from first principles , underst and ing of the determinants of the external validity of an RCT requires clinical rather than statistical expertise , and often depends on a detailed underst and ing of the particular clinical condition under study and its management in routine clinical practice . However , reliable judgments about the external validity of RCTs are essential if treatments are to be used correctly in as many patients as possible in routine clinical practice . The results of RCTs or systematic review s will never be relevant to all patients and all setting s , but they should be design ed and reported in a way that allows clinicians to judge to whom the results can reasonably be applied . Table 1 lists some of the important potential determinants of external validity , each of which is review ed briefly below . Many of the considerations will only be relevant in certain types of trials , for certain interventions , or in certain clinical setting s , but they can each sometimes undermine external validity . Moreover , the list is not exhaustive and requires more detailed annotation and explanation than is possible in this short review . Table 1 Main Issues That Can Affect External Validity and Should Be Addressed in Reports of the Results of R and omised Controlled Trials or Systematic Review s and Considered by Clinicians Some of the issues that determine external validity are relevant to the distinction between pragmatic trials and explanatory trials [ 2 ] , but it would be wrong to assume that pragmatic trials necessarily have greater external validity than explanatory trials . For example , broad eligibility criteria , limited collection of baseline data , and inclusion of centres with a range of expertise and differing patient population s have many advantages , but they can also make it very difficult to generalise the overall average effect of treatment to a particular clinical setting The results of a r and omized clinical trial can be reported using relative and /or absolute estimators of treatment effect . These various measures convey different information , and the choice can influence the physician 's appreciation of the size of treatment effect and , subsequently , treatment decisions . We compare the estimators with respect to the clinical ly relevant information conveyed to physicians , and identify which clinical questions can and can not be answered directly by each . We also identify opportunities for misinterpretation when one estimator is substituted for another , or when an estimator is mislabeled . Clinical ly important questions are addressed most directly by reporting both relative and absolute effects using relative risk and its complement , relative risk reduction , and risk difference and its reciprocal , number needed to treat . This is true of estimates of treatment effect derived from a single trial and also from meta- analysis of a group of trials . Because the control group 's risk affects the numerical value of the odds ratio , the odds ratio can not substitute for the risk ratio in conveying clinical ly important information to physicians . This is especially important when large treatment effects are shown in trials carried out in population s at high baseline risk Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 
    Output:
    
Results The general verdict from the check list type evaluations in nine relevant systematic review s was that Burke et al. ( 1991 ) is a good quality trial .
All relevant meta-analyses extensively used its data to formulate therapeutic evidence .
My comprehensive evaluation , on the other h and , brought to the surface a series of serious problems in the design , conduct , analysis and report of this trial that were missed by the earlier evaluations .
Conclusion A check-list or instrument based approach , if used as a short-cut , may at times rate deeply flawed trials as good quality trials .