Systematic Reviews
Contribution to the Cochrane Pregnancy and Childbirth Group
The Cochrane Pregnancy and Childbirth Group was the first review group within the Cochrane Collaboration, and remains the largest with over 600 published reviews and protocols. The unit contributes to this group as Editor (Lelia Duley), and Review Author (Lelia Duley, Jim Thornton), for over 30 reviews. The topics covered by these Cochrane Reviews include prevention and treatment of hypertensive disorders of pregnancy, care during childbirth, and diagnosis of gestational diabetes.
Contact: Lelia Duley
Status: Ongoing
Publications: 2009-8; 2011-4; 2011-8; 2012-2; 2012-6; 2012-12; 2012-16; 2013-3; 2013-4; 2013-8; 2013-9; 2013-15; 2014-13; 2014-32; 2015-3; 2015-38; 2015-46;
Ethics issues in recruitment of sick and preterm infants to randomised trials
Recruitment of preterm or sick infants to trials requires approaching parents at a particularly difficult time, often with a tight timescale for making a decision. This raises challenges for obtaining informed consent to such research, especially issues regarding competence, understanding, time and voluntariness for parents reaching a decision. On the other hand if the problem of consent is not successfully addressed, this risks becoming an ‘orphan’ area of research. The review is relatively novel, combining approaches across the disciplinary divide between philosophy and social science. The aim is to identify the ethical challenges and potential solutions, in order to inform the design and conduct of future trials. The project is led by Chris Megone (University of Leeds).
Contact: Lelia Duley
Funding: NIHR Programme grants for applied research
Status: Analysis and reporting
Publications: 2014-30; 2015-40;
Developing and expanding the methodology of IPD meta-analysis
This project is using data from 32,217 women and their 32,819 babies enrolled in 31 randomised trials of prevention of pre-eclampsia to explore and develop the methods used in both individual patient data (IPD) and aggregate data systematic reviews. The aim is to explore and develop both practical and statistical methods: specific to synthesis of data from pregnancy and childbirth (linkage between mothers and babies and dealing with multiple pregnancies); generally applicable to the conduct of IPD meta-analysis (one or two stage analysis, fixed or random effects, subgroup or modelling based approach to exploring potential effect modifiers/treatment interactions, dealing with sparse and missing data; methods relating all types of systematic review (selective reporting of outcomes, the utility of meta-regression). It will also explore why early trial results often appear more promising than those that follow.
The project is led by Lesley Stewart (University of York). Collaborators include Doug Altman (University of Oxford), Lisa Askie (University of Sydney), and Gavin Stewart (University of York).
Contact: Lelia Duley
Funding: MRC
Status: Analysis and write up
Prospective meta-analysis of alternative strategies for placental transfusion at very preterm birth
Internationally, the meta-register of controlled trials lists several planned or ongoing trials of timing of cord clamping that include preterm births. This project has formed a collaborative group of these trialists, which has developed and agreed the protocol for prospective meta-analysis. The review has been registered with Prospero (CRD42013004405) the international prospective register of systematic reviews (see http://www.crd.york.ac.uk/prospero/). As the trials scheduled to be part of this meta-analysis are due to be completed at different times, the analysis plan will include at least two cycles of analysis. The first collaborators' meeting for trialists is scheduled for April 2015. The project is a collaboration with Lisa Askie, William Tarnow-Mordi and John Simes at the University of Sydney.
Contact: Lelia Duley
Funding: NIHR Programme grants for applied research
Status: Set up
Methodology
Site Identification and Selection
Careful site selection methods and tools, such as questionnaires, have evolved to become "best" practice in the commercial and non-commercial clinical trials setting. However, there is little evidence of the value of such strategies, and there is no generally accepted model or tool to use when identifying potential sites and deciding which to include in a trial.
The Nottingham Clinical Trials Unit developed a simple template site selection questionnaire in 2010. This includes both generic questions about research experience and capacity to study specific questions based on requirements of the trial protocol. These questionnaires have been piloted in four multi-centre trials in the UK. This pilot project is assessing how well the questionnaire predicts performance against pre-specified recruitment targets at each site.
To describe strategies in current use for identifying and selecting trial sites for randomised trials, we have also conducted a survey of Chief Investigators for trials funded by the National Institute for Health Research, and of UK Trial Managers' Network members.
Contact: Diane Whitham
Status: Ongoing
Publications: 2013-16; 2015-54; 2015-56
Consent for Emergency Trials
Offering participation in a randomised trial during a clinical emergency can be challenging for both clinicans and participants. We developed an oral assent two stage pathway to offer participation in the Cord Pilot Trial to women having a very preterm birth. This was for use when birth was imminent, and was used for almost one third of women recruited to the trial.In collaboration with Susan Ayers, City University, we have conducted qualitative interviews to assess the views and experiences of clinicians and women of the two consent pathways in this trial.
Contact: Lelia Duley
Funding: NIHR Programme Grants for Applied Research
Status: Analysis and Reporting
Recruitment and Retention
In collaboration with the University of Manchester, we are conducting two embedded randomised trials of a multi-media website intervention to enhance recruitment into the seAFOod and HiLight trials. These embedded trials are both part of the MRC-funded Systematic Techniques for Assisting Recruitment to trials (START) study.
A further study embedded in the BEEP trial is evaluating two interventions to enhance retention of participants and collection of outcome data at follow up. This study has a factorial design, and will assess the effects of SMS notification before sending questionnaires and of timing of a voucher payment.
Contact: Alan Montgomery
Status: Ongoing
Adjudication in Stroke Trials
Central adjudication in clincial trials involves a committee of independent assessors re-evaluating data reported by onsite trial staff in order to standardise outcome assessment and reduce bias. However, this procedure can be time consuming and expensive, and may or may not alter the classification of site-reported events. Currently there is a lack of evidence to guide when an adjudication committee should be used in a clinical trial.
Working in collaboration with the Stroke Trials Unit, we conducted secondary analyses of a large stroke trial to investigate the impact adjudication had on the trial results. Statistical simulations were used to establish how the effect of adjudication would change if the accuracy of site diagnosis varied. Further work is being developed to establish when adjudication may or may not be important to include in a clinical trial.
Contact: Pete Godolphin
Funding: NIHR Research Methods Fellowship
Status: Ongoing
Adjudication of Neonatal Cranial Ultrasound Scans
There is substantial variation between individuals in reporting the findings of cranial ultrasound scans. This could have important implications for clinical trials that use diagnoses assessed by cranial ultrasound as a outcome measure. Trials of cord clamping at very preterm birth have suggested there may be an effect on intraventricular haemorrhage, which in these trials was a diagnosis based on cranial ultrasound scan. However these trials have not reported clearly how the ultrasound data were collected and assessed. Often a mix of people will conduct and report the scans, and both the quality of the scans and their interpretation is variable in clinical practice.
This study aimed to provide standardised, independent adjudication of the cranial ultrasound scans for babies recruited to the Cord Pilot Trial, and to allow assessment of the intra-and inter-observer reliability of the scan interpretation.
Contact: Lucy Bradshaw
Funding: NIHR Programme Grant for Applied Research
Status: Analysis and Reporting