Kerry Woolfall

Under-reporting of foetal alcohol spectrum disorders: an analysis of hospital episode statistics

BackgroundInternationally, 0.97 per 1,000 live births are affected by foetal alcohol syndrome (FAS). However, prevalence intelligence has been limited in the UK, hindering the development of appropriate services. This analysis compares hospital admissions over time, between regions and with alcohol-related admissions for adult females to assess whether established patterns (such as the North experiencing elevated harms) can be identified.MethodsA retrospective analysis of hospital admissions data (April 2002 to March 2008) for foetal alcohol spectrum disorder (FASD)-related conditions: foetal alcohol syndrome (dysmorphic) (n = 457); foetus and newborn affected by maternal use of alcohol (n = 157); maternal care for (suspected) damage to foetus from alcohol (n = 285); and 322,161 women admitted due to alcohol-related conditions.ResultsWhilst the rate of admission for alcohol-related conditions in women aged 15-44 years increased significantly by 41% between 2002/03 and 2007/08 (p < 0.0001), significant increases were only seen in the numbers of FAS. Established regional rates of admission for alcohol-related conditions in women aged 15-44 years old were not associated with admission for FASD-related conditions.ConclusionsIt would be expected that the North West and North East regions, known to have higher levels of alcohol harm would have higher levels of FASD-related conditions. However, this was not reflected in the incidence of such conditions, suggesting under-reporting. With incomplete datasets, intelligence systems are severely limited, hampering efforts to develop targeted interventions. Improvements to intelligence systems, practitioner awareness and screening are essential in tackling this.

Doing challenging research studies in a patient-centred way: a qualitative study to inform a randomised controlled trial in the paediatric emergency care setting

Objective To inform the design of a randomised controlled trial (called EcLiPSE) to improve the treatment of children with convulsive status epilepticus (CSE). EcLiPSE requires the use of a controversial deferred consent process. Design Qualitative interview and focus group study. Setting 8 UK support groups for parents of children who have chronic or acute health conditions and experience of paediatric emergency care. Participants 17 parents, of whom 11 participated in telephone interviews (10 mothers, 1 father) and 6 in a focus group (5 mothers, 1 father). 6 parents (35%) were bereaved and 7 (41%) had children who had experienced seizures, including CSE. Results Most parents had not heard of deferred consent, yet they supported its use to enable the progress of emergency care research providing a childs safety was not compromised by the research. Parents were reassured by tailored explanation, which focused their attention on aspects of EcLiPSE that addressed their priorities and concerns. These aspects included the safety of the interventions under investigation and how both EcLiPSE interventions are used in routine clinical practice. Parents made recommendations about the appropriate timing of a recruitment discussion, the need to individualise approaches to recruiting bereaved parents and the use of clear written information. Conclusions Our study provided information to help ensure that a challenging trial was patient centred in its design. We will use our findings to help EcLiPSE practitioners to: discuss potentially threatening trial safety information with parents, use open-ended questions and prompts to identify their priorities and concerns and clarify related aspects of written trial information to assist understanding and decision-making.

Parents’ Agendas in Paediatric Clinical Trial Recruitment Are Different from Researchers’ and Often Remain Unvoiced: A Qualitative Study

Ensuring parents make an informed decision about their child’s participation in a clinical trial is a challenge for practitioners as a parent’s comprehension of a trial may differ from that intended by the practitioners responsible for recruitment. We explored what issues parents consider important when making a decision about participation in a paediatric clinical trial and their comprehension of these issues to inform future recruitment practice. This qualitative interview and observational study examined recruitment in four placebo-controlled, double-blind randomised clinical trials of medicines for children. Audio-recorded trial recruitment discussions between practitioners and parents (N = 41) were matched with semi-structured interviews with parents (N = 41). When making a decision about trial entry parents considered clinical benefit, child safety, practicalities of participation, research for the common good, access to medication and randomisation. Within these prioritised issues parents had specific misunderstandings, which had the potential to influence their decisions. While parents had many questions and concerns about trial participation which influenced their decision-making, they rarely voiced these during discussions about the trials with practitioners. Those involved in the recruitment of children to clinical trials need to be aware of parents’ priorities and the sorts of misunderstandings that can arise with parents. Providing trial information that is tailored to what parents consider important in making a decision about a clinical trial may improve recruitment practice and ultimately benefit evidence-based paediatric medicine.

Standard 1: Consent and Recruitment

A 4-year-old boy with a serious metabolic disorder is eligible for a trial of a new enzyme replacement, the first potential option to treat this disease. His parents have little understanding of the disease or trial, even with careful explanation, but eventually they consent to entry in the trial. The treating clinician doubts whether their consent is valid. This and similar dilemmas face pediatricians in research every day. Many of the therapeutic options for children have not been tested with the rigor applied to similar treatments in adults. This highlights the need for research to improve the evidence base of childrens medicine, for more pediatricians to undertake research, and for more children and families to participate.1 … Address correspondence to Martin Offringa, MD, PhD, Senior Scientist and Program Head, Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: martin.offringa{at}sickkids.ca

How should individual participant data (IPD) from publicly funded clinical trials be shared

BackgroundIndividual participant data (IPD) from completed clinical trials should be responsibly shared to support efficient clinical research, generate new knowledge and bring benefit to patients. The Medical Research Council (MRC) Hubs for Trials Methodology Research (HTMR) has developed guidance to facilitate the sharing of IPD from publicly funded clinical trials.MethodsDevelopment of the guidance was completed over four phases which included a focussed review of policy documents, a web-based survey of the UK Clinical Research Collaboration (CRC) Registered Clinical Trials Units (CTU) Network, participation of an expert committee and an open consultation with the UKCRC Registered CTU Network. The project was funded by the MRC HTMR (MR/L004933/1-R39).ResultsGood practice principles include: (i) the use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access; (ii) seeking consent for sharing IPD from trial participants in all future clinical trials with adequate assurance that patient privacy and confidentiality can be maintained; and (iii) establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organisations and users of IPD. The guidance has been endorsed by Cancer Research UK, MRC Methodology Research Programme Advisory Group, Wellcome Trust and the Executive Group of the UKCRC Registered CTU Network. The National Institute for Health Research (NIHR) has confirmed it is supportive of the application of this guidance.ConclusionsImplementation of these principles will improve transparency, increase the coherent sharing of IPD from publicly funded trials, and help publicly funded trials to adhere to trial funder and journal requirements for data sharing.

UK publicly funded Clinical Trials Units supported a controlled access approach to share individual participant data but highlighted concerns

Objectives Evaluate current data sharing activities of UK publicly funded Clinical Trial Units (CTUs) and identify good practices and barriers. Study Design and Setting Web-based survey of Directors of 45 UK Clinical Research Collaboration (UKCRC)–registered CTUs. Results Twenty-three (51%) CTUs responded: Five (22%) of these had an established data sharing policy and eight (35%) specifically requested consent to use patient data beyond the scope of the original trial. Fifteen (65%) CTUs had received requests for data, and seven (30%) had made external requests for data in the previous 12 months. CTUs supported the need for increased data sharing activities although concerns were raised about patient identification, misuse of data, and financial burden. Custodianship of clinical trial data and requirements for a CTU to align its policy to their parent institutes were also raised. No CTUs supported the use of an open access model for data sharing. Conclusion There is support within the publicly funded UKCRC-registered CTUs for data sharing, but many perceived barriers remain. CTUs are currently using a variety of approaches and procedures for sharing data. This survey has informed further work, including development of guidance for publicly funded CTUs, to promote good practice and facilitate data sharing.

How parents and practitioners experience research without prior consent (deferred consent) for emergency research involving children with life threatening conditions: a mixed method study.

Objective Alternatives to prospective informed consent to enable children with life-threatening conditions to be entered into trials of emergency treatments are needed. Across Europe, a process called deferred consent has been developed as an alternative. Little is known about the views and experiences of those with first-hand experience of this controversial consent process. To inform how consent is sought for future paediatric critical care trials, we explored the views and experiences of parents and practitioners involved in the CATheter infections in CHildren (CATCH) trial, which allowed for deferred consent in certain circumstances. Design Mixed method survey, interview and focus group study. Participants 275 parents completed a questionnaire; 20 families participated in an interview (18 mothers, 5 fathers). 17 CATCH practitioners participated in one of four focus groups (10 nurses, 3 doctors and 4 clinical trial unit staff). Setting 12 UK childrens hospitals. Results Some parents were momentarily shocked or angered to discover that their child had or could have been entered into CATCH without their prior consent. Although these feelings resolved after the reasons why consent needed to be deferred were explained and that the CATCH interventions were already used in clinical care. Prior to seeking deferred consent for the first few times, CATCH practitioners were apprehensive, although their feelings abated with experience of talking to parents about CATCH. Parents reported that their decisions about their childs participation in the trial had been voluntary. However, mistiming the deferred consent discussion had caused distress for some. Practitioners and parents supported the use of deferred consent in CATCH and in future trials of interventions already used in clinical care. Conclusions Our study provides evidence to support the use of deferred consent in paediatric emergency medicine; it also indicates the crucial importance of practitioner communication and appropriate timing of deferred consent discussions.

A patient and public involvement (PPI) toolkit for meaningful and flexible involvement in clinical trials - a work in progress.

Plain Language SummaryFunders of research are increasingly requiring researchers to involve patients and the public in their research. Patient and public involvement (PPI) in research can potentially help researchers make sure that the design of their research is relevant, that it is participant friendly and ethically sound. Using and sharing PPI resources can benefit those involved in undertaking PPI, but existing PPI resources are not used consistently and this can lead to duplication of effort. This paper describes how we are developing a toolkit to support clinical trials teams in a clinical trials unit. The toolkit will provide a key ‘off the shelf’ resource to support trial teams with limited resources, in undertaking PPI. Key activities in further developing and maintaining the toolkit are to:● listen to the views and experience of both research teams and patient and public contributors who use the tools;● modify the tools based on our experience of using them;● identify the need for future tools;● update the toolkit based on any newly identified resources that come to light;● raise awareness of the toolkit and● work in collaboration with others to either develop or test out PPI resources in order to reduce duplication of work in PPI.AbstractBackground Patient and public involvement (PPI) in research is increasingly a funder requirement due to the potential benefits in the design of relevant, participant friendly, ethically sound research. The use and sharing of resources can benefit PPI, but available resources are not consistently used leading to duplication of effort. This paper describes a developing toolkit to support clinical trials teams to undertake effective and meaningful PPI. Methods The first phase in developing the toolkit was to describe which PPI activities should be considered in the pathway of a clinical trial and at what stage these activities should take place. This pathway was informed through review of the type and timing of PPI activities within trials coordinated by the Clinical Trials Research Centre and previously described areas of potential PPI impact in trials.In the second phase, key websites around PPI and identification of resources opportunistically, e.g. in conversation with other trialists or social media, were used to identify resources. Tools were developed where gaps existed. Results A flowchart was developed describing PPI activities that should be considered in the clinical trial pathway and the point at which these activities should happen. Three toolkit domains were identified: planning PPI; supporting PPI; recording and evaluating PPI. Four main activities and corresponding tools were identified under the planning for PPI: developing a plan; identifying patient and public contributors; allocating appropriate costs; and managing expectations. In supporting PPI, tools were developed to review participant information sheets. These tools, which require a summary of potential trial participant characteristics and circumstances help to clarify requirements and expectations of PPI review. For recording and evaluating PPI, the planned PPI interventions should be monitored in terms of impact, and a tool to monitor public contributor experience is in development. Conclusions This toolkit provides a developing ‘off the shelf’ resource to support trial teams with limited resources in undertaking PPI. Key activities in further developing and maintaining the toolkit are to: listen to the views and experience of both research teams and public contributors using the tools, to identify the need for future tools, to modify tools based on experience of their use; to update the toolkit based on any newly identified resources that come to light; to raise awareness of the toolkit and to work in collaboration with others to both develop and test out PPI resources in order to reduce duplication of work in PPI.

Good practice principles for sharing individual participant data from publicly funded clinical trials

Sharing Individual Participant Data (IPD) from completed clinical trials offers numerous well recognised advantages that can advance clinical research and benefit patients. The clinical trial community, including publicly funded trials, has a duty to facilitate this process. In our recent survey, publicly funded clinical trials units (CTUs) from the UKCRC registered CTUs network were supportive of the principle of sharing IPD. However, concerns were also raised including complex and varied sponsorship arrangements of the trials they coordinate, inappropriate reuse of clinical trial data, additional resource required for CTUs to prepare and share data, potential loss of ability to publish further research, and the potential risk to trial participant privacy. The CTUs preferred the use of a controlled access approach, with systems in place to review data access requests from researchers. We have used the results of this survey, input from an expert committee and an open consultation involving the UKCRC registered CTUs to inform the development of a guidance document summarising good practice principles for sharing IPD and associated documentation from publicly-funded clinical trials. The guidance has been endorsed by Cancer Research UK, MRC Methodology Research Programme Advisory Group, Wellcome Trust and the Executive Group of the UK CRC Registered CTUs Network. The National Institute for Health Research (NIHR) has confirmed it is supportive of the application of this guidance.

Clinical Trial Decisions in Difficult Circumstances: Parental Consent Under Time Pressure

Treatments and interventions used to care for children in emergencies should be based on strong evidence. Well-designed clinical trials investigating these interventions for children are therefore indispensable. Parental informed consent is a key ethical requirement for the enrollment of children in such studies. However, if time is limited because of an urgent need for intervention, there are additional ethical challenges to adequately support the informed consent process. The acute situation and associated psychological impact may compromise the ability of parents to give informed consent. Little evidence exists to guide the process of consent seeking for a child’s research participation when time is limited. It is also unclear in what circumstances alternatives to prospective informed consent could be applied. This article describes possible options to manage the informed consent process in an appropriate, practical, and, we believe, ethical way when time is limited.