***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 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 Investigators should properly calculate sample sizes before the start of their r and omised trials and adequately describe the details in their published report . In these a-priori calculations , determining the effect size to detect -- eg , event rates in treatment and control groups -- reflects inherently subjective clinical judgments . Furthermore , these judgments greatly affect sample size calculations . We question the br and ing of trials as unethical on the basis of an imprecise sample size calculation process . So-called underpowered trials might be acceptable if investigators use method ological rigor to eliminate bias , properly report to avoid misinterpretation , and always publish results to avert publication bias . Some shift of emphasis from a fixation on sample size to a focus on method ological quality would yield more trials with less bias . Unbiased trials with imprecise results trump no results at all . Clinicians and patients deserve guidance now Background Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment . We report three controlled trials of interventions to increase recruitment to the Txt2stop trial . Purpose To evaluate : Trial 1 . The impact on registration s of a text message regarding an online registration facility ; Trial 2 . The impact on r and omizations of sending £ 5 with a covering letter to those eligible to join the trial ; Trial 3 . The impact on r and omizations of text messages containing quotes from existing participants . Methods Single blind controlled trials with allocation concealment . Interventions : Trial 1 : A text message regarding our new online registration facility ; Trial 2 : A letter with £ 5 enclosed ; Trial 3 : A series of four text messages containing quotes from participants . The control group in each trial received st and ard Txt2stop procedures . Results Trial 1 : 3.6 % ( 17/470 ) of the intervention group and 1.1 % ( 5/467 ) of the control group registered for the trial , risk difference 2.5 % ( 95 % CI 0.6—4.5 ) . 0 % ( 0/ 470 ) of the intervention group and 0.2 % ( 1/467 ) of the control group registered successfully online , risk difference —0.2 ( 95 % CI —0.6—0.2 ) ; Trial 2 : 4.5 % ( 11/246 ) of the intervention group and 0.4 % ( 1/245 ) of the control group were r and omized into the Txt2stop trial , risk difference 4.0 % ( 95 % CI 1.4—6.7 ) ; Trial 3 : 3.5 % ( 14/405 ) of the intervention group and 0 % ( 0/406 ) of the control group were r and omized into the Txt2stop trial , risk difference 3.5 ( 95 % CI 1.7—5.2 ) . Limitations There were no baseline data available for trial 1 . Allocation of participant IDs in trials 2 and 3 were systematic . Conclusion Sending a text message about an online registration facility increased registration s to Txt2stop , but did not increase online registration s. Sending a £ 5 reimbursement for participants ’ time and sending text messages containing quotes from existing participants increased r and omizations into the Txt2stop trial . Clinical Trials 2010 ; 7 : 265—273 . Background Trials increasingly experience problems in recruiting participants . Underst and ing the causes of poor recruitment is critical to developing solutions . We interviewed people who had declined a trial of an innovative psychological therapy for depression ( REFRAMED ) about their response to the trial invitation , in order to underst and their decision and identify ways to improve recruitment . Methods Of 214 people who declined the trial , 35 ( 16 % ) gave permission to be contacted about a qualitative study to explore their decision . Analysis of transcripts of semi-structured interviews was informed by grounded theory . Results We interviewed 20 informants : 14 women and six men , aged 18 to 77 years . Many interviewees had prior experience of research participation and positive views of the trial . Interviewees ’ decision making resembled a four-stage sequential process ; in each stage they either decided not to participate in the trial or progressed to the next stage . In stage 1 , interviewees assessed the invitation in the context of their experiences and attitudes ; we term those who opted out at this stage ‘ prior decliners ’ as they had an established position of declining trials . In stage 2 , interviewees assessed their own eligibility ; those who judged themselves ineligible and opted out at this stage are termed ‘ self-excluders ’ . In stage 3 , interviewees assessed their need for the trial therapy  and potential to benefit ; we term those who decided they did not need the trial therapy and opted out at this stage ‘ treatment decliners ’ . In stage 4 , interviewees deliberated the benefits and costs of trial participation ; those who opted out after judging that disadvantages outweighed advantages are termed ‘ trial decliners ’ . Across all stages , most individuals declined because they judged themselves ineligible or not in need of the trial therapy . While ‘ prior decliners ’ are unlikely to respond to any trial recruitment initiative , the factors leading others to decline are amenable to amelioration as they do not arise from a rejection of trials or a personal stance . Conclusions To improve recruitment in similar trials , the most successful interventions are likely to address patients ’ assessment s of their eligibility and their potential to benefit from the trial treatment , rather than reducing trial burden . Trial registration International St and ard R and omised Controlled Trial Number : IS RCT N85784627 . Registration date 10 August 2011 It is now well known that st and ard statistical procedures become invali date d when applied to cluster r and omized trials in which the unit of inference is the individual . A result ing consequence is that research ers conducting such trials are faced with a multitude of design choices , including selection of the primary unit of inference , the degree to which clusters should be matched or stratified by prognostic factors at baseline , and decisions related to cluster subsampling . Moreover , application of ethical principles developed for individually r and omized trials may also require modification . We discuss several topics related to these issues , with emphasis on the choices that must be made in the planning stages of a trial and on some potential pitfalls to be avoided Background The blood pressure rapid intensive lowering and normal treatment for mood and cognition in persistent depression ( BRILiANT mood study ) was devised as a pilot study to investigate the feasibility and safety of intensive blood pressure lowering as treatment for persistent mood and cognitive symptoms in older adults with major depressive disorder and to assess the availability of this population for recruitment . In addition , the relationship between reduced blood pressure and the change in cerebral blood flow and mood was to be investigated . Methods A single centre pilot r and omised controlled trial ( RCT ) , with two parallel groups of intensive or normal treatment for hypertension , recruiting from primary and secondary care and newspaper advert , with an aim of recruiting 66 participants , was observed in this study . At the end of the recruitment period , in order to explore the reasons for failure to recruit to target , surveys were developed and issued to those involved in recruitment . Results Recruitment rates were lower than expected which led to the study being exp and ed to further areas and opened to self-referral via advertisement . However , because of better management of hypertension due to changes in the UK Quality and Outcomes Framework guidelines for blood pressure treatment , few eligible patients were identified and the study closed at the end of the recruitment period , with 13 participants consenting , but 12 failing screening result ing in one recruited participant . Conclusions Overall , the BRILiANT mood study was found not to be feasible , and results suggest that the expected patient population no longer exists . To overcome such recruitment difficulties , a prompt commencement of a study after funding so no relevant care changes occur might help prevent similar problems in future studies . In addition , self-referral , in this case via advertisement in papers , may be a useful tool to increase response rate . When recruiting in primary care , direct access to primary care data bases , in a secure and anonymised way , may enable more effective screening . Ultimately , the BRILiANT mood study was shown not to be feasible ; this was a useful conclusion from this pilot study .Trial Registration IS RCT N 64524251 ; UKCRN Portfolio No : PURPOSE Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population . This study hypothesized that use of an easy-to-read consent statement , when compared with a st and ard consent statement , will result in higher patient comprehension of the clinical treatment protocol , lower patient anxiety , higher patient satisfaction , and higher patient accrual . METHODS A r and omized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups . Institutions were r and omly assigned to administer either an easy-to-read consent statement or the st and ard consent statement to patients being recruited to participate in selected cancer treatment trials .  Telephone interviews were conducted with a total of 207 patients to assess study outcomes . RESULTS Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm . Patient comprehension and state anxiety were not affected by the intervention . Accrual rates into the parent studies also did not differ significantly between the two study groups . CONCLUSION Clinical trial informed consent statements can be modified to be easier to read without omitting critical information . Patient anxiety and satisfaction can be affected by the consent document . The generalizability of these study results is limited by the characteristics of the patient sample . Ninety percent of the sample were white women , and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64 , indicating a literacy level at or above the ninth grade Background Patient underst and ing of study information is fundamental to gaining informed consent to take part in a r and omised controlled trial . In order to meet the requirements of research ethics committees , patient information material s can be long and need to communicate complex messages . There is concern that st and ard approaches to providing patient information may deter potential participants from taking part in trials . The Systematic Techniques for Assisting Recruitment to Trials ( MRC-START ) research programme aims to test interventions to improve trial recruitment . The aim of this study was to investigate the effect on recruitment of optimised patient information material s ( with improved readability and ease of comprehension ) compared with st and ard material s. The study was embedded within two primary care trials involving patients with long-term conditions . Methods The Healthlines Study involves two linked trials evaluating a telehealth intervention  in patients with depression ( Healthlines Depression ) or raised cardiovascular disease risk ( Healthlines CVD ) . We conducted two trials of a recruitment intervention , embedded within the Healthlines host trials . Patients identified as potentially eligible in each of the Healthlines trials were r and omised  to receive either the  original patient information material s or optimised versions of these material s. Primary outcomes were the proportion of participants r and omised ( Healthlines Depression ) and the proportion expressing interest in taking part ( Healthlines CVD ) . Results In Healthlines Depression ( n = 1364 ) , 6.3 % of patients receiving the optimised patient information material  s were r and omised into the study compared to 4.0 % in those receiving st and ard material s ( OR = 1.63 , 95 % CI = 1.00 to 2.67 ) . In Healthlines CVD ( n = 671 ) 24.0 % of those receiving optimised patient information material s responded positively to the invitation to participate , compared to 21.9 % in those receiving st and ard material s ( OR = 1.12 , 95 % CI = 0.78 to 1.61 ) . Conclusions Evidence from these two embedded trials suggests limited benefits of optimised patient information material s on recruitment rates , which may only be apparent in some patient population s , with no effects on other outcomes . Further embedded trials are needed to provide a more precise estimate of effect , and to explore further how effects vary by trial context , intervention , and patient population .Trial registration Current Controlled Trials : Healthlines Depression ( IS RCT N27508731 ) on 26 June 2012 ; and Healthlines CVD ( IS RCT N14172341 ) on 5 July Background Recruitment and retention of participants are critical to the success of 
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We did not find a positive impact of directly advertising PPIR on any other outcomes .
Conclusion To our knowledge , this is the largest ever embedded trial to evaluate a recruitment or PPIR intervention .
Advertising PPIR did not improve enrolment rates or any other outcome .
It is possible that rather than advertising PPIR being the means to improve recruitment , PPIR may have an alternative impact on trials by making them more attractive , acceptable and patient-centred .