***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 
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    Input: Background A commonly reported problem with the conduct of multicentre r and omised controlled trials ( RCTs ) is that recruitment is often slower or more difficult than expected , with many trials failing to reach their planned sample size within the timescale and funding originally envisaged . The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies : the UK Medical Research Council ( MRC ) and the Health Technology Assessment ( HTA ) Programme . Methods The cohort of trials was identified from the administrative data bases held by the two funding bodies . 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria . The full scientific applications and subsequent trial reports su bmi tted by the trial teams to the funders provided the principal data sources . Associations between trial characteristics and recruitment success were tested using the Chi-squared test , or Fisher 's exact test where appropriate . Results Less than a third ( 31 % ) of the trials achieved their original recruitment target and half ( 53 % ) were awarded an extension . The proportion achieving targets did not appear to improve over time . The overall start to recruitment was delayed in 47 ( 41 % ) trials and early recruitment problems were identified in 77 ( 63 % ) trials . The inter-relationship between trial features and recruitment success was complex . A variety of strategies were employed to try to increase recruitment , but their success could not be assessed . Conclusion Recruitment problems are complex and challenging . Many of the trials in the cohort experienced recruitment difficulties . Trials often required extended recruitment periods ( sometimes supported by additional funds ) . While this is of continuing concern , success in addressing the trial question may be more important than recruitment alone OBJECTIVE To study the effectiveness of ventilation tubes on the language development in infants with persistent otitis media with effusion ( OME ) . All existing studies addressed children 3 years of age or older . Currently , OME is detected and treated with ventilation tubes at a younger age . Because of the critical relationship between age , hearing , and language development , we conducted a study of the effects of ventilation tubes on language development in infants 1 to 2 years old with persistent OME . DESIGN A multicenter , r and omized , controlled trial ( embedded in a cohort ) with 2 treatment arms : 1 ) treatment with ventilation tubes  ( VT group ; n = 93 ) ; or 2 ) with a period of watchful waiting ( WW group ; n = 94 ) . Hearing loss and expressive and comprehensive language were assessed every 6 months , while tympanometry and otoscopy were performed every 3 months . Other factors with potential influence on language development were also included : adenoidectomy , hospital , attending day care , sex , age at r and omization , educational level of the mother , upper respiratory infections , and the native country of the parents and older siblings . The trial was design ed to allow for the detection of a mean difference in language development of 3 months or more between children allocated to the VT and WW groups . RESULTS No relevant differences were found in expressive or comprehensive language between the 2 groups after adjustment for educational level of the mother , IQ of the child , and differences at baseline . A principal component analysis showed that in the VT group , the children with frequent complaints improved 1.6 months more in comprehensive language than those with no or some complaints . The children with favorable language stimulation , however , did not improve more than the children with less favorable stimulation . No differences were found for expressive language among the various clusters . The probability to improve > 3 months in comprehensive language was.48 ( 95 % confidence interval [CI]:.29-.68 ) for children with highly educated mothers versus.09 ( 95 % CI:.02-.30 ) for children whose mothers had a low educational level . In the WW group , these changes were.30 ( 95 % CI:.14-.53 ) and .14 ( 95 % CI:.04-.35 ) , respectively . The probability to improve > 4 months in expressive language was.52 ( 95 % CI:.32-.71 ) for children with highly educated mothers versus.06 ( 95 % CI:.01-.31 ) for children whose mothers had a low educational level . In the WW group these changes were.42 ( 95 % CI:.23-.64 ) and .11 ( 95 % CI:.03-.35 ) , respectively . In addition , there were delays in expressive language in both groups compared with their age expected values . The comprehensive language of the children who were effusion-free during the follow-up ( n = 54 ) improved 1.5 months ( 95 % CI : -.2 - 3.2 ) more than that of the children who had persistent effusion during the entire follow-up ( n = 28 ) . No differences were found for expressive language development . Disregarding the intervention contrast , improvements in hearing seemed to be related to improvements in language development , especially in verbal comprehension . DISCUSSION In this study , we used the  Reynell , Schlichting , and Lexi tests  to study the relation between early persistent OME and language development . These tests are directly related to normal language , widely accepted , and vali date d. It can not be ruled out that more specific measures such as auditory perception tests would have produced more differences between groups , but the focus was on general language development . A total of 10 children in the WW group received treatment with ventilation tubes during follow-up . A further 11 children dropped out during the trial . A sensitivity analysis with the 10 children who received ventilation tubes did not change the results , and baseline differences were not found between the 11 children who dropped out and those who completed the trial . CONCLUSIONS In the total group of infants with persistent OME , ventilation tubes did not Objective : To assess whether continuous consent , a process in which information is given to research participants at different stages in a trial , and clinician training in that process were effective when used by clinicians while gaining consent to the  Total Body Hypothermia ( TOBY ) trial . The TOBY trial is a r and omised controlled trial ( RCT ) investigating the use of whole-body cooling for neonates with evidence of perinatal asphyxia . Obtaining valid informed consent for the TOBY trial is difficult , but is a good test of the effectiveness of continuous consent . Methods : Semistructured interviews were conducted with 30 sets of parents who consented to the TOBY trial and with 10 clinicians who sought it by the continuous consent process . Analysis was focused on the validity of parental consent based on the consent components of competence , information , underst and ing and voluntariness . Results : No marked problems with consent validity at the point of signature were observed in 19 of 27 ( 70 % ) couples . Problems were found mainly to lie with the competence and underst and ing of the parents : mothers , particularly , had problems with competence in the early stages of consent . Problems in underst and ing were primarily to do with side effects . Problems in both competence and underst and ing were observed to reduce markedly , particularly for mothers , in the post-signature phase , when further discussion took place . R and omisation was generally understood but unpopular . Information was not always given by clinicians in stages during the short period available before parents gave consent . Most clinicians , however , were able to give follow-up information . Discussion : Consent validity was found to compare favourably with similar trials examined in the Euricon study . Conclusion : Adopting the elements of the continuous consent process and clinician training in RCTs should be considered by research ers , particularly when they have concerns about the quality of consent they are likely to obtain by using a conventional process Objectives : R and omized clinical trials that enroll patients in critical or emergency care ( acute care ) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent . To assess the extent that recruitment challenges lead to r and omized clinical trial discontinuation , we compared the discontinuation of acute care and nonacute care r and omized clinical trials . Design : Retrospective cohort of 894 r and omized clinical trials approved by six institutional review boards in Switzerl and , Germany , and Canada between 2000 and 2003 . Setting : R and omized clinical trials involving patients in an acute or nonacute care setting . Subjects and Interventions : We recorded trial characteristics , self-reported trial discontinuation , and self-reported reasons for discontinuation from protocol s , corresponding publications , institutional review board files , and a survey of investigators . Measurements and Main Results : Of 894 r and omized clinical trials , 64 ( 7 % ) were acute care r and omized clinical trials ( 29 critical care and 35 emergency care ) . Compared with the 830 nonacute care r and omized clinical trials , acute care r and omized clinical trials were more frequently discontinued ( 28 of 64 , 44 % vs 221 of 830 , 27 % ; p = 0.004 ) . Slow recruitment was the most frequent reason for discontinuation , both in acute care ( 13 of 64 , 20 % ) and in nonacute care r and omized clinical trials ( 7 of 64 , 11 % ) . Logistic regression analyses suggested the acute care setting as an independent risk factor for r and omized clinical trial discontinuation specifically as a result of slow recruitment ( odds ratio , 4.00 ; 95 % CI , 1.72–9.31 ) after adjusting for other established risk factors , including nonindustry sponsorship and small sample size . Conclusions : Acute care r and omized clinical trials are more vulnerable to premature discontinuation than nonacute care r and omized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment . These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in r and omized clinical trials conducted in the critical and emergency care setting The objective was to study the generalizability of trial results by comparing  r and omized patients to eligible but nonr and omized patients who received the same management .  Implementation of trial results is only justifiable when the results can be generalized to the total domain population . The design was a multicentre r and omized controlled trial on the effect of early screening and treatment with ventilation tubes on infants with otitis media with effusion . R and omized ( n = 187 ) and nonr and omized eligible patients ( n = 133 ) were followed up . The study population comprised children who were detected by auditory screening at the age of 9 - 12 months and who were subsequently diagnosed with persistent bilateral otitis media with effusion for 4 - 6 months . A significant difference was found in the distribution of some prognostic factors : more r and omized children had older siblings , did not attend day care and had mothers with a lower educational level than the nonr and omized children . These factors , however , did not modify the outcome . No differences were found in mean hearing levels between the r and omized and nonr and omized children : in both the r and omized and nonr and omized children ventilation tubes improved the hearing level , especially after 6 months . However , in the long term ( 12 months ) , the hearing levels were equal again . The results of the r and omized and nonr and omized patients were comparable . The results of this trial appear to be generalizable to the total domain population . The procedure of following up both r and omized and nonr and omized patients is recommended when there is concern about selective participation and reduced generalizability BACKGROUND Extracorporeal membrane oxygenation ( ECMO ) is a complex and expensive technology that can be used to provide temporary support during respiratory failure . Its value for mature newborn infants is controversial because of varying interpretation of the available evidence . We undertook a collaborative trial throughout the UK to assess whether a policy of referral for ECMO has a beneficial effect on survival to 1 year without severe disability in comparison with conventional management . METHODS Between 1993 and 1995 , 185 mature ( gestational age at birth > or = 35 weeks , birthweight > or = 2 kg ) newborn infants with severe respiratory failure ( oxygenation index > or = 40 ) were enrolled from 55 hospitals in a r and omised comparison of either referral to one of five specialist centres for consideration of ECMO or continued intensive conventional management at the original hospital . The most common diagnoses were persistent pulmonary hypertension due to meconium aspiration , congenital diaphragmatic hernia , isolated persistent fetal circulation , sepsis , and idiopathic respiratory distress syndrome . Of the infants allocated ECMO , 84 % received this support . Recruitment to the trial was stopped early ( November , 1995 ) by the trial steering committee on the advice of the independent data -monitoring committee , because the data accumulated showed a clear advantage with ECMO .  124 children were enrolled before December , 1994 ; those who survived to 1 year of age have undergone  neurological assessment  at that age ( by one of three developmental paediatricians unaware of treatment allocation ) . FINDINGS Overall , 81 ( 44 % ) infants died before leaving hospital , and two are known to have died later . Death rates differed between the two trial groups ; 30 of 93 infants allocated ECMO died compared with 54 of 92 allocated conventional care . The relative risk was 0.55 ( 95 % Cl 0.39 - 0.77 ; p = 0.0005 ) , which is equivalent to one extra survivor for every three to four infants allocated ECMO . The difference in survival applied irrespective of the primary diagnosis , disease severity , and type of referral centre . The benefit of ECMO was also found for the primary outcome measure of death or disability at 1 year ( among 124 children enrolled before December , 1994 ) . One child in each group has severe disability ( overall Griffiths ' developmental quotient < 50 , or untestable ) , and 16 ( ten ECMO , six conventional management ) have impairments with a lesser degree of disability . INTERPRETATION These preliminary results demonstrate the 
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Conclusions Families often have treatment preferences which may affect trial recruitment .
Whilst children appear to hold treatment preferences , this is rarely reported .