Characterising meaningful patient and public involvement in the pharmaceutical industry research setting: a retrospective quality assessment.

OBJECTIVES: Patient and public involvement (PPI) in clinical research has a well-established infrastructure in the UK, and while there has been good progress within pharmaceutical-industry-sponsored research, further improvements are still needed. This review aims to share learnings from quality assessments of historical PPI projects within Pfizer UK to inform future projects and drive PPI progress in the pharmaceutical industry. DESIGN AND SETTING: Internal assessments of Pfizer UK PPI projects were conducted to identify all relevant projects across the medicines development continuum between 2017 and 2021. Five sample projects were developed into case studies. OUTCOME MEASURE: Retrospective quality assessments were performed using the Patient Focused Medicines Development (PFMD) Patient Engagement Quality Guidance (PEQG) tool. Recommendations for improvement were developed. RESULTS: Retrospective case study analysis and quality framework assessment revealed benefits of PPI to both Pfizer UK and to external partners, as well as challenges and learnings to improve future practice. Recommendations for improvement based on these findings focused on processes and procedures for PPI, group dynamics and diversity for PPI activities, sharing of expertise, the importance of bidirectional and timely feedback, and the use of understandable language in materials. CONCLUSIONS: PPI in medicines development is impactful and beneficial but is still being optimised in the pharmaceutical industry. Using the PFMD PEQG tool to define gaps, share learnings and devise recommendations for improvement helps to ensure that PPI is genuine and empowering, rather than tokenistic. Ultimately, these recommendations should be acted on to further embed PPI as an integral part of medicines development and health research within the pharmaceutical industry. This article includes a plain language summary in the supplement.

Patient and public involvement in research: the need for budgeting PPI staff costs in funding applications.

BACKGROUND: Patient and Public Involvement (PPI) groups are becoming more established as collaborators with academic researchers and institutions to ensure that research is important and relevant to end users, and to identify areas that might have ethical considerations, as well as to advise on solutions. The National Institute for Health and Care Research UK Standards for Public Involvement in Research embody best practice for PPI, including support and learning opportunities that build confidence and skills for members of the public to play an invaluable and mutually productive role in research. However, the pivotal role of research and professional services (management and administrative) staff within academic institutions for sustaining and making this involvement successful is often overlooked. MAIN BODY: It takes significant effort to develop and sustain effective PPI in research. The six UK Standards for Public Involvement highlight the need for consistent, inclusive, well-governed and mutually respectful working relationships to sustain effective PPI contributions in health research. Productivity across a team of lay and academic members requires organisation and experience of implementing these standards by a dedicated PPI team, yet advice on PPI finances is usually focused on costs for patient panel members, and budgets in funding applications rarely consider the wider PPI team behind this involvement. As an exemplar, we reflect on how the Asthma UK Centre for Applied Research (AUKCAR) has developed a dedicated PPI Platform, with guidance for how PPI should be embedded throughout the research lifecycle, and detailed information to support the costing of PPI in funding applications. AUKCAR's work with established researchers, as well as Early Career Researchers and PhD students, is at the heart of a campaign to raise awareness of the importance of PPI in effective research planning. CONCLUSION: Focusing attention on the staff behind best practice involvement in health research may stimulate a much-needed discussion to ensure flourishing PPI capacity, with significant patient and public benefit. With adaptation, the PPI expertise within AUKCAR can be translated more widely.

Patient and Public Involvement (PPI) is important for high-quality research. It makes research more relevant to patients, and makes the results more useful for the health service. To make patient involvement effective, we need skilled staff with experience of involving lay members in research, as well as engaging researchers in PPI activities. There is little guidance about staff time needed to recruit and support lay members and researchers properly. This means that we still do not understand the true cost of including patients and the public in research, and we often under cost this in funding applications. As an example, we reflect on how the Asthma UK Centre for Applied Research (AUKCAR) has organised staff to support for its patient involvement. We give some thoughts on how to cost PPI staff time in funding applications. By focusing attention on the team behind the lay volunteers, we hope to encourage a much-needed discussion about the support involved, and deliver more patient benefits. The AUKCAR experience can be adapted to other research topics and contexts.

Studying the Long-term Impact of COVID-19 in Kids (SLICK). Healthcare use and costs in children and young people following community-acquired SARS-CoV-2 infection: protocol for an observational study using linked primary and secondary routinely collected healthcare data from England, Scotland and Wales.

INTRODUCTION: SARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs. METHODS AND ANALYSIS: We will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection. ETHICS AND DISSEMINATION: This study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway.

Offer of a bandage versus rigid immobilisation in 4- to 15-year-olds with distal radius torus fractures: the FORCE equivalence RCT.

BACKGROUND: Torus (buckle) fractures of the wrist are the most common fractures in children involving the distal radius and/or ulna. It is unclear if children require rigid immobilisation and follow-up or would recover equally as well by being discharged without any immobilisation or a bandage. Given the large number of these injuries, identifying the optimal treatment strategy could have important effects on the child, the number of days of school absence and NHS costs. OBJECTIVES: To establish whether or not treating children with a distal radius torus fracture with the offer of a soft bandage and immediate discharge (i.e. offer of a bandage) provides the same recovery, in terms of pain, function, complications, acceptability, school absence and resource use, as treatment with rigid immobilisation and follow-up as per usual practice (i.e. rigid immobilisation). DESIGN: A pragmatic, multicentre, randomised controlled equivalence trial. SETTING: Twenty-three UK emergency departments. PARTICIPANTS: A total of 965 children (aged 4-15 years) with a distal radius torus fracture were randomised from January 2019 to July 2020 using a secure, centralised, online-encrypted randomisation service. Exclusion criteria included presentation > 36 hours after injury, multiple injuries and an inability to complete follow-up. INTERVENTIONS: A bandage was offered to 489 participants and applied to 458, and rigid immobilisation was carried out in 476 participants. Participants and clinicians were not blinded to the treatment allocation. MAIN OUTCOME MEASURES: The pain at 3 days post randomisation was measured using the Wong-Baker FACES Pain Rating Scale. Secondary outcomes were the patient-reported outcomes measurement system upper extremity limb score for children, health-related quality of life, complications, school absence, analgesia use and resource use collected up to 6 weeks post randomisation. RESULTS: A total of 94% of participants provided primary outcome data. At 3 days, the primary outcome of pain was equivalent in both groups. With reference to the prespecified equivalence margin of 1.0, the adjusted difference in the intention-to-treat population was -0.10 (95% confidence interval -0.37 to 0.17) and the per-protocol population was -0.06 (95% confidence interval -0.34 to 0.21). There was equivalence of pain in both age subgroups (i.e. 4-7 years and 8-15 years). There was no difference in the rate of complications, with five complications (1.0%) in the offer of a bandage group and three complications (0.6%) in the rigid immobilisation group. There were no differences between treatment groups in functional recovery, quality of life or school absence at any point during the follow-up. Analgesia use was marginally higher at day 1 in the offer of a bandage group than it was in the rigid immobilisation group (83% vs. 78% of participants), but there was no difference at other time points. The offer of a bandage significantly reduced the cost of treatment and had a high probability of cost-effectiveness at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year. LIMITATIONS: Families had a strong pre-existing preference for the rigid immobilisation treatment. Given this, and the inability to blind families to the treatment allocation, observer bias was a concern. However, there was clear evidence of equivalence. CONCLUSIONS: The study findings support the offer of a bandage in children with a distal radius torus fracture. FUTURE WORK: A clinical decision tool to determine which children require radiography is an important next step to prevent overtreatment of minor wrist fractures. There is also a need to rationalise interventions for other common childhood injuries (e.g. 'toddler's fractures' of the tibia). TRIAL REGISTRATION: This trial is registered as ISRCTN13955395 and UKCRN Portfolio 39678. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 33. See the NIHR Journals Library website for further project information.

BACKGROUND: Torus fractures (also called buckle fractures) of the wrist are the most common type of broken bone in children, affecting 60,000 children in the UK per year. They are the mildest form of broken bone, in which the bone crushes (or buckles). Despite these fractures being so common, there is no 'standard treatment'. The traditional treatment is to use a plaster cast and arrange outpatient follow-up. Recent medical research has suggested that wearing a bandage, or even having no treatment, might result in similar healing. In this study, we looked into whether or not a bandage (which was optional to wear) and no further follow-up resulted in the same recovery as a hard splint and usual follow-up. A total of 965 children aged 4­15 years from 23 emergency departments in the UK took part in the study. Children were evenly divided between the bandage and hard splint groups in a process called randomisation. Prior to the study, families told us that managing pain after injury was the most important issue to them. We asked children and their families to tell us about pain, recovery using the arm, quality of life, complications encountered and school absences. We also looked at the financial costs to families and the NHS. WHAT DID THE TRIAL FIND?: The two treatments resulted in the same outcomes. The majority of those offered a bandage chose to wear it immediately. There was no difference at all in the levels of pain between those treated with a hard splint and usual outpatient follow-up and those offered a bandage and discharge (i.e. no further follow up) from hospital the same day. Similarly, there was no difference in the recovery using the arm, quality of life, complications encountered or school absences. There was a very slight increase in pain killer use in the bandage group at day 1, but not at any other time point. Overall, the cost of the offer of a bandage was slightly lower for families and the NHS. In conclusion, the findings of this study support offering a bandage to be used at the discretion of families to treat children with a torus fracture of the wrist.

Keeping patient and public partnership at the heart of medical technology development during Covid-19: examples of adaptive practice.

NIHR (National Institute for Health Research) Devices for Dignity MedTech Cooperative (D4D) and NIHR Children and Young People MedTech Cooperative (CYPMedTech) have established track records in keeping patient and public involvement (PPI) at the core of medical technology development, evaluation and implementation. The 2020 global COVID-19 pandemic presented significant challenges to maintaining this crucial focus. In this paper we describe prior successful methodologies and share examples of the adaptations made in order to continue to engage with patients and the public throughout the pandemic and beyond. We reflect on learning gained from these experiences, and new areas of scope and focus relating to broadening the reach of engagement and representation, along with associated resource requirements and impact metrics.

Routine gastric residual volume measurement to guide enteral feeding in mechanically ventilated infants and children: the GASTRIC feasibility study.

BACKGROUND: The routine measurement of gastric residual volume to guide the initiation and delivery of enteral feeding is widespread in paediatric intensive care and neonatal units, but has little underlying evidence to support it. OBJECTIVE: To answer the question: is a trial of no gastric residual volume measurement feasible in UK paediatric intensive care units and neonatal units? DESIGN: A mixed-methods study involving five linked work packages in two parallel arms: neonatal units and paediatric intensive care units. Work package 1: a survey of units to establish current UK practice. Work package 2: qualitative interviews with health-care professionals and caregivers of children admitted to either setting. Work package 3: a modified two-round e-Delphi survey to investigate health-care professionals' opinions on trial design issues and to obtain consensus on outcomes. Work package 4: examination of national databases to determine the potential eligible populations. Work package 5: two consensus meetings of health-care professionals and parents to review the data and agree consensus on outcomes that had not reached consensus in the e-Delphi study. PARTICIPANTS AND SETTING: Parents of children with experience of ventilation and tube feeding in both neonatal units and paediatric intensive care units, and health-care professionals working in neonatal units and paediatric intensive care units. RESULTS: Baseline surveys showed that the practice of gastric residual volume measurement was very common (96% in paediatric intensive care units and 65% in neonatal units). Ninety per cent of parents from both neonatal units and paediatric intensive care units supported a future trial, while highlighting concerns around possible delays in detecting complications. Health-care professionals also indicated that a trial was feasible, with 84% of staff willing to participate in a trial. Concerns expressed by junior nurses about the intervention arm of not measuring gastric residual volumes were addressed by developing a simple flow chart and education package. The trial design survey and e-Delphi study gained consensus on 12 paediatric intensive care unit and nine neonatal unit outcome measures, and identified acceptable inclusion and exclusion criteria. Given the differences in physiology, disease processes, environments, staffing and outcomes of interest, two different trials are required in the two settings. Database analyses subsequently showed that trials were feasible in both settings in terms of patient numbers. Of 16,222 children who met the inclusion criteria in paediatric intensive care units, 12,629 stayed for > 3 days. In neonatal units, 15,375 neonates < 32 weeks of age met the inclusion criteria. Finally, the two consensus meetings demonstrated 'buy-in' from the wider UK neonatal communities and paediatric intensive care units, and enabled us to discuss and vote on the outcomes that did not achieve consensus in the e-Delphi study. CONCLUSIONS AND FUTURE WORK: Two separate UK trials (one in neonatal units and one in paediatric intensive care units) are feasible to conduct, but they cannot be combined as a result of differences in outcome measures and treatment protocols, reflecting the distinctness of the two specialties. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42110505. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 23. See the NIHR Journals Library website for further project information.

Nurses looking after babies and children on intensive care units in the UK usually pass a tube and aspirate whatever food or fluid is in the baby's stomach before they give a feed. The idea is to ensure that the stomach is not overdistended with food and prevent the baby vomiting or, worse, aspirating food into the lungs. However, there is little justification for this practice. It is rarely done in many other countries. It may not be pleasant for the child and perhaps is unnecessary. Some experts have suggested that the policy should be evaluated in a randomised controlled trial. This would mean allocating a large number of children at random to either have the stomach aspirated before feeds, or not. Such a trial would be a major undertaking and we are unsure if parents or staff would be willing to allow children to participate. The aim of this study was to see if it is possible to conduct such a large trial in the UK. Two surveys (of 119 units) showed us that regularly measuring the stomach contents when starting and increasing feeds is common practice for both newborn and older children in UK intensive care units. However, in some countries, such as France, this practice is rarely done. We asked 31 parents and 51 health-care professionals about a future study. Overall, parents were supportive of a trial if it was explained to them well by a knowledgeable and caring professional, and if they were approached at the right time. Some concerns were expressed about not picking up complications early if gastric residual volume was not measured. Health-care professionals were also mainly positive about a future trial, but mentioned similar concerns about not picking up complications early and the difficulty of changing a long-standing routine practice. Parents suggested study outcomes that were important to them. These, along with other outcomes, were voted on in a further survey of 106 professionals and at face-to-face meetings involving 41 participants. Overall, our findings suggest that a trial is feasible to perform and acceptable to parents. However, because of differences in both treatments and important outcomes between children's intensive care units and newborn baby intensive care units, two trials would be needed, one in each type of intensive care unit. These two trials will test whether or not the benefits of not measuring gastric residual volume (e.g. improved calorie intake) outweigh the potential harms (e.g. delayed diagnosis of complications).

Guidance on development and operation of Young Persons' Advisory Groups.

BACKGROUND: Engaging patients and the public as collaborators in research is increasingly recognised as important as such partnerships can help improve research relevance and acceptability. Young Persons' Advisory Groups (YPAGs) provide a forum for clinical researchers and triallists to engage with children and young people on issues relevant to the design, conduct and translation of paediatric clinical trials. Until fairly recently, there was very little information available to guide the successful development and operation of YPAGs. OBJECTIVE: To develop an evidence-based tool to guide clinical researchers and triallists in the establishment and operation of a YPAG. METHODS: An online needs assessment survey was conducted using SurveyMonkey with 60 known paediatric drug researchers to identify knowledge gaps around YPAG engagement, development and operation. Semistructured interviews with founders and coordinators of five well-established existing YPAGs and a review of the literature were performed to identify best-practice processes for starting up and operating YPAG. RESULTS: The majority of 12 survey respondents (20%) from 12 different centres indicated that while they felt YPAGs could benefit their research, guidance on how to develop and operate a YPAG was needed. Most preferred a web-based guidance tool. Ten core steps in starting up and operating a YPAG were identified and developed into an online YPAG guidance tool, now freely accessible for use by paediatric clinical researchers worldwide. Plans to evaluate the impact are in place. CONCLUSIONS: This novel tool, developed with an internationally based group of public involvement leads working across paediatric clinical research areas, provides harmonised guidance for researchers seeking to develop and operate YPAGs to help improve the quality and impact of paediatric clinical research studies.

NIHR Clinical Research Networks: what they do and how they help paediatric research.

This review provides paediatricians with an update on the new structure of the National Institute for Health Research's (NIHR) Clinical Research Network (CRN): Children and its role within the wider NIHR infrastructure. The network supports delivery of high-quality research within the NHS in England and supports researchers, through provision of staff and resources, with feasibility, site set-up, patient recruitment and study management. Since 2013, over 80% of commercial contract studies running within the UK sat within the UKCRN Portfolio. Of the diverse, increasing portfolio of studies supported by the network, many studies are interventional, with 33% being randomised controlled studies. Recruitment to studies supported by the network through the Children's Portfolio has consistently improved. Over 200 000 participants have been recruited to the Children's Portfolio studies to date, and there are currently approximately 500 studies open to recruitment. The CRN: Children has successfully involved patients and the public in all aspects of study design and delivery, including through the work of Generation R. Challenges remain in conducting paediatric research and the network is committed to supporting Children's research and further building on its achievements to date. Education and engagement of paediatricians within the network and research is important to further improving quality and delivery of paediatric research.

From plans to actions in patient and public involvement: qualitative study of documented plans and the accounts of researchers and patients sampled from a cohort of clinical trials.

UNLABELLED: : Patient and public involvement (PPI) in research is increasingly required, although evidence to inform its implementation is limited. OBJECTIVE: Inform the evidence base by describing how plans for PPI were implemented within clinical trials and identifying the challenges and lessons learnt by research teams. METHODS: We compared PPI plans extracted from clinical trial grant applications (funded by the National Institute for Health Research Health Technology Assessment Programme between 2006 and 2010) with researchers' and PPI contributors' interview accounts of PPI implementation. Analysis of PPI plans and transcribed qualitative interviews drew on the Framework technique. RESULTS: Of 28 trials, 25 documented plans for PPI in funding applications and half described implementing PPI before applying for funding. Plans varied from minimal to extensive, although almost all anticipated multiple modes of PPI. Interview accounts indicated that PPI plans had been fully implemented in 20/25 trials and even expanded in some. Nevertheless, some researchers described PPI within their trials as tokenistic. Researchers and contributors noted that late or minimal PPI engagement diminished its value. Both groups perceived uncertainty about roles in relation to PPI, and noted contributors' lack of confidence and difficulties attending meetings. PPI contributors experienced problems in interacting with researchers and understanding technical language. Researchers reported difficulties finding 'the right' PPI contributors, and advised caution when involving investigators' current patients. CONCLUSIONS: Engaging PPI contributors early and ensuring ongoing clarity about their activities, roles and goals, is crucial to PPI's success. Funders, reviewers and regulators should recognise the value of preapplication PPI and allocate further resources to it. They should also consider whether PPI plans in grant applications match a trial's distinct needs. Monitoring and reporting PPI before, during and after trials will help the research community to optimise PPI, although the need for ongoing flexibility in implementing PPI should also be recognised.

Patient and public involvement in the early stages of clinical trial development: a systematic cohort investigation.

BACKGROUND: Randomised controlled trials (RCTs) are considered particularly likely to benefit from patient and public involvement (PPI). Decisions made by professional researchers at the outset may go on to have a significant impact on the potential for PPI contributions. OBJECTIVE: To increase knowledge of PPI within the early development of RCTs by systematically describing the reported level, nature and acceptability of proposed PPI to the funders. METHODS: Documentation from the outline application process for all RCTs that received funding from the Health Technology Assessment (HTA) Programme 2006-2010 was requested. For each application, data were extracted on trial characteristics, references to PPI in the development of the outline application and funding Board feedback, and plans for PPI in the full application and after the trial was funded. RESULTS: 110 applications were eligible with outline applications available for 90 (82%). The cohort covered a wide range of interventions and conditions. 54% (49/90) provided some information about PPI. 26 (28.9%) indicated PPI within the development of the outline application itself; 32 (35.6%) planned involvement in the full application and 43 (48%) once the trial was funded. Recruitment at diagnosis and surgical interventions were less likely to describe PPI. Blinded trials and trials in which participants may receive placebo only, more frequently described PPI activity. The HTA commissioning Board feedback rarely referred to PPI. CONCLUSIONS: Incorporation of PPI within the development of the outline application or specification of plans for future involvement was low. Funder requests for applicants to provide information on PPI and justification for its absence should be welcomed but further research is needed to identify the impact of this on its contributions to research. Comments on PPI by reviewers should be directional rather than state that an increase is required. Challenges facing applicants in initiating PPI prior to funding need to be addressed.