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Evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. The lack of transparent reporting impedes readers from judging the reliability and validity of trial findings, researchers from extracting information for systematic reviews and results in research waste. The Consolidated Standards of Reporting Trials (CONSORT) Statement was developed to improve the reporting of randomised controlled trials. Within-person trials are a particular type of trial for conditions that can affect two or more body sites, and are a useful and efficient tool because the comparisons between interventions are within-persons. Such trials are more commonly conducted in ophthalmology, dentistry and dermatology. The reporting of within-person trials has, however, been variable and incomplete, hindering their usefulness in clinical decision making and by future researchers. This document presents the CONSORT extension to within-person trials. It aims to facilitate the reporting of within-person trials. CONSORT within-person extends 16 items of the CONSORT 2010 checklist, and introduces a modified flowchart and baseline table to enhance transparency. Examples of good reporting and evidence-based rationale for CONSORT within-person checklist items are provided.

Background:\ud \ud Family Nurse Partnership (FNP) is a home-based nurse home-visiting programme to support vulnerable parents. Group Family Nurse Partnership (gFNP) has similar aims and materials and was demonstrated to be feasible in implementation evaluations.\ud Objectives:\ud \ud To determine whether or not gFNP, compared with usual care, could reduce risk factors for maltreatment in a vulnerable group and be cost-effective.\ud Design:\ud \ud A multisite randomised controlled parallel-group trial and prospective economic evaluation, with eligible women allocated (minimised by site and maternal age group) to gFNP or usual care.\ud Setting:\ud \ud Community locations in the UK.\ud Participants:\ud \ud Expectant mothers aged

BACKGROUND: Trials of inhaled nitric oxide (iNO) used short term in preterm infants with severe respiratory failure have to date shown no evidence of benefit, and there have been no trials reporting follow-up to 4 years of age. The INNOVO trial recruited 108 infants (55 iNO arm and 53 controls) from 15 neonatal units. By 1 year of age 59% had died, and 84% of the survivors had signs of impairment or disability. OBJECTIVE: This paper reports the long-term clinical effectiveness and costs of adding NO to the ventilator gases of preterm infants with severe respiratory failure. PATIENTS AND METHODS: Children were assessed at age 4-5 years by interview, examination, cognitive and behavioural assessments. The outcome data were divided into seven domains and were described as normal, impaired or disabled (mild, moderate or severe) by the degree of functional loss. RESULTS: 38 of the 43 survivors had follow-up assessments. In the iNO group 62% (34/55) had died or were severely disabled, compared to 70% (37/53) in the no iNO group (RR 0.89, 95% CI 0.67 to 1.16). There was no evidence of difference in the levels of impairment or disability between the two groups in any of the domains studied, or of cost differences, amongst the survivors. CONCLUSION: For this group of babies with severe respiratory failure there was no evidence of difference in the longer-term outcome between those babies allocated to iNO and those who were allocated to no iNO. The challenge is to identify those premature babies who are able to respond to NO with clinically important health improvements. TRIAL REGISTRATION NUMBER: 17821339.

Background: The subject of death and bereavement in the context of randomised controlled trials in neonatal or paediatric intensive care is under-researched. The objectives of this phase of the Bereavement and RAndomised ControlLEd Trials (BRACELET) Study were to determine trial activity in UK neonatal and paediatric intensive care (2002-06); numbers of deaths before hospital discharge; and variation in mortality across intensive care units and trials and to determine whether bereavement support policies were available within trials. These are essential prerequisites to considering the implications of future policies and practice subsequent to bereavement following a child's enrolment in a trial.Methods: The units survey involved neonatal units providing level 2 or 3 care, and paediatric units providing level II care or above; the trials survey involved trials where allocation was randomized and interventions were delivered to intensive care patients, or to parents but designed to affect patient outcomes.Results: Information was available from 191/220 (87%) neonatal units (149 level 2 or 3 care); and 28/32 (88%) paediatric units. 90/177 (51%) eligible responding units participated in one or more trial (76 neonatal, 14 paediatric) and 54 neonatal units and 6 paediatric units witnessed at least one death. 50 trials were identified (36 neonatal, 14 paediatric). 3,137 babies were enrolled in neonatal trials, 210 children in paediatric trials. Deaths ranged 0-278 (median [IQR interquartile range] 2 [1, 14.5]) per neonatal trial, 0-4 (median [IQR] 1 [0, 2.5]) per paediatric trial. 534 (16%) participants died post-enrolment: 522 (17%) in neonatal trials, 12 (6%) in paediatric trials. Trial participants ranged 1-236 (median [IQR] 21.5 [8, 39.8]) per neonatal unit, 1-53 (median [IQR] 11.5 [2.3, 33.8]) per paediatric unit. Deaths ranged 037 (median [IQR] 3.5 [0.3, 8.8]) per neonatal unit, 0-7 (median [IQR] 0.5 [0, 1.8]) per paediatric unit. Three trials had a formal policy for responding to bereavement.Conclusions: A substantial number of deaths after trial enrolment were identified, distributed over many trials and units. Few trial teams had responses to bereavement in place. Those with the largest numbers of deaths might be best placed to collaborate in developing and assessing responses to bereavement.

OBJECTIVES: To identify factors associated with good and poor recruitment to multicentre trials. DATA SOURCES: Part A: database of trials started in or after 1994 and were due to end before 2003 held by the Medical Research Council and Health Technology Assessment Programmes. Part B: interviews with people playing a wide range of roles within four trials that their funders identified as 'exemplars'. Part C: a large multicentre trial (the CRASH trial) of treatment for head injury. REVIEW METHODS: The study used a number of different perspectives ('multiple lenses'), and three components. Part A: an epidemiological review of a cohort of trials. Part B: case studies of trials that appeared to have particularly interesting lessons for recruitment. Part C: a single, in-depth case study to examine the feasibility of applying a business-orientated analytical framework as a reference model in future trials. RESULTS: In the 114 trials found in Part A, less than one-third recruited their original target within the time originally specified, and around one-third had extensions. Factors observed more often in trials that recruited successfully were: having a dedicated trial manager, being a cancer or drug trial, and having interventions only available inside the trial. The most commonly reported strategies to improve recruitment were newsletters and mailshots, but it was not possible to assess whether they were causally linked to changes in recruitment. The analyses in Part B suggested that successful trials were those addressing clinically important questions at a timely point. The investigators were held in high esteem by the interviewees, and the trials were firmly grounded in existing clinical practices, so that the trial processes were not alien to clinical collaborators, and the results could be easily applicable to future practice. The interviewees considered that the needs of patients were well served by participation in the trials. Clinical collaborators particularly appreciated clear delineation of roles, which released them from much of the workload associated with trial participation. There was a strong feeling from interviewees that they were proud to be part of a successful team. This pride fed into further success. Good groundwork and excellent communications across many levels of complex trial structures were considered to be extremely important, including training components for learning about trial interventions and processes, and team building. All four trials had faced recruitment problems, and extra insights into the working of trials were afforded by strategies invoked to address them. The process of the case study in Part C was able to draw attention to a body of research and practice in a different discipline (academic business studies). It generated a reference model derived from a combination of business theory and work within CRASH. This enabled identification of weaker managerial components within CRASH, and initiatives to strengthen them. Although it is not clear, even within CRASH, whether the initiatives that follow from developing and applying the model will be effective in increasing recruitment or other aspects of the success of the trial, the reference model could provide a template, with potential for those managing other trials to use or adapt it, especially at foundation stages. The model derived from this project could also be used as a diagnostic tool if trials have difficulties and hence as a basis for deciding what type of remedial action to take. It may also be useful for auditing the progress of trials, such as during external review. CONCLUSIONS: While not producing sufficiently definitive results to make strong recommendations, the work here suggests that future trials should consider the different needs at different phases in the life of trials, and place greater emphasis on 'conduct' (the process of actually doing trials). This implies learning lessons from successful trialists and trial managers, with better training for issues relating to trial conduct. The complexity of large trials means that unanticipated difficulties are highly likely at some time in every trial. Part B suggested that successful trials were those flexible and robust enough to adapt to unexpected issues. Arguably, the trialists should also expect agility from funders within a proactive approach to monitoring ongoing trials. Further research into different recruitment patterns (including 'failures') may help to clarify whether the patterns seen in the 'exemplar' trials differ or are similar. The reference model from Part C needs to be further considered in other similar and different trials to assess its robustness. These and other strategies aimed at increasing recruitment and making trials more successful need to be formally evaluated for their effectiveness in a range of trials.

BACKGROUND: Research studies are essential to improving healthcare. However, many fail to recruit their planned number of participants. There are many interventions that researchers try to improve recruitment. Finding which ones are effective would be of benefit to the research community and society. OBJECTIVES: To quantify the effects of strategies to improve participation in research studies. SEARCH STRATEGY: We aimed to find all randomized and quasi-randomized controlled trials of strategies to improve recruitment to research studies. We searched nine electronic databases and manually searched the reference lists of relevant trials. We assessed the eligibility of each trial using pre-defined criteria. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of methods to increase recruitment in research studies. This includes non-healthcare studies. Studies that required only questionnaire completion were excluded. DATA COLLECTION AND ANALYSIS: We extracted data on the method evaluated, nature of the population, nature of the study to be recruited into, randomisation or quasi-randomisation method, allocation concealment, numbers and proportions in each arm. We used risk ratios and their 95% confidence intervals to describe the effects in individual trials, and assessed heterogeneity of these ratios between trials. MAIN RESULTS: We identified 15 eligible trials, including a total of 33,719 participants. All strategies were aimed at participants for healthcare studies. No strategies were identified at the level of researcher collaborators or ethics committees. Because of heterogeneity between trials and within strategies, the results were not synthesised. Trials of monetary incentives, an additional questionnaire at invitation and treatment information on the consent form demonstrated benefit; these specific interventions from individual trials are not easily generalizable. AUTHORS' CONCLUSIONS: On this evidence, it is not possible to predict the effect most interventions will have on recruitment. Funders and researchers should ensure that the evaluation of recruitment strategies are incorporated into research studies.

An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising.\ud \ud

BACKGROUND: Pethidine is the most widely used intra-muscular opioid for the relief of labour pain. However concerns have been raised about its effectiveness and the possibility of depressing respiration in newborns. OBJECTIVES: The objective of this review was to assess the effects of different opioids (and different doses of the same opioid) administered intra-muscularly in labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 1997) and reference lists of articles. SELECTION CRITERIA: Randomised trials comparing the effects of different currently used opioids (and different doses of the same opioid) administered intramuscularly in labour for women who request systemic analgesia. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. Analysis was based on the groups as randomly allocated. MAIN RESULTS: Sixteen trials were included. There were problems with methodological quality of some of the trials, and lack of consistency in the way various outcomes were reported. There was no evidence of a difference between pethidine and tramadol in terms of pain relief, interval to delivery, or instrumental or operative delivery. There appeared to be more adverse effects such as nausea and vomiting and drowsiness with pethidine. Maternal pain relief seemed almost identical between the meptazinol and pethidine groups, whether assessed as maternal satisfaction with pain relief, visual analogue scales, or use of other pain relief, but meptazinol gave rise to slightly more side effects. Maternal satisfaction with pain relief appeared similar for pentazocine and pethidine, with more frequent nausea and vomiting with pethidine. AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate the comparative efficacy and safety of the various opioids used for analgesia in labour.

There is considerable variation in the use of cortisosteroids within Europe before possible preterm delivery. Thyrotropin releasing hormone is rarely used as synergistic treatment in most, but not all, European countries—presumably reflecting uncetainty about the effectiveness and safety of this agent.

OBJECTIVES: To determine whether the addition of antenatal thyrotrophin-releasing hormone (TRH) to corticosteroids, given to women at risk of preterm delivery, would decrease the risk of death and severe morbidity associated with prematurity. DESIGN: Two concurrent multicentre, double blind, randomised, placebo-controlled trials were designed with a common core dataset to be analysed as a single large pragmatic trial. SETTING: Hospital maternity units. POPULATIONS: Pregnant women at risk of preterm delivery who had been prescribed a course of corticosteroids to enhance fetal maturation. INTERVENTIONS: Antenatal administration of TRH 400 microg every eight hours for four doses versus matching placebo. MAIN OUTCOME MEASURES: Primary: death of the baby or chronic lung disease (defined as oxygen dependency at 28 days after birth). Secondary: other measures of respiratory morbidity, in particular respiratory distress syndrome. Other measures of short term neonatal morbidity including intraventricular haemorrhage and necrotising enterocolitis. Measures of maternal side effects. RESULTS: The antenatal TRH trial was halted early on the basis of external evidence. Overall a total of 225 women were recruited who delivered 275 babies. The primary outcome of death or chronic lung disease occurred in 33 babies in the TRH group and 43 babies in the placebo group (RR 0.8, 95% CI 0.5-1.2). There were no other differences between the two groups. Stratified analysis did not reveal any differences between the two groups depending on how long before the time of delivery the mother had received the TRH or placebo. CONCLUSIONS: These trials are too small to provide convincing evidence of the effect of antenatal TRH on neonatal outcome. When added to the existing systematic review and meta-analysis, however, these data should provide evidence on which subsequent practice can be based. The process by which the trials were monitored and stopped is of relevance to future trials