The use of healthcare systems data for RCTs

Abstract Background Healthcare systems data (HSD) has the potential to optimise the efficiency of randomised controlled trials (RCTs), by decreasing trial-specific data demands. Therefore, the use of HSD in trials is expected to increase. In 2019, it was estimated that 47% of NIHR-funded trials were planning to use HSD. We aim to understand the extent and nature of its current use and its evolution over time. Methods We identified a cohort of RCTs within the NIHR Journals Library that commenced after 2019 and were described as being in progress on 6 June 2022. Details on the source and use of HSD were extracted from eligible RCTs. The use of HSD was categorised according to whether it was used as the sole data source for outcomes and whether the outcomes were primary or secondary. HSD is often insufficient for patient-reported outcomes (PROs). We aimed to determine methods used by trialists for collecting PRO data alongside HSD. Results Of the 84 eligible studies, 52 (62%) planned to use HSD and 79 (94%) planned to collect PROs. The number of RCTs planning to use HSD for at least one outcome was 28 (54%) with 24 of these planning to use HSD as the sole data source for at least one outcome. The number of studies planning to use HSD for primary and secondary outcomes was 10 (20%) and 21 (40%) respectively. The sources of HSD were National Health Service (NHS) Digital (n = 37, 79%), patient registries (n = 7, 29%), primary care (n = 5, 21%), The Office for National Statistics (ONS) (n = 3, 13%) and other (n = 2, 8%). PROs were collected for 92% of the trials planning to use HSD. Methods for collection of PROs included in-person (n = 26, 54%), online (n = 22, 46%), postal (n = 18, 38%), phone (n = 14, 29%) and app (n = 2, 4%). Conclusions HSD is being used in around two thirds of the studies but cannot yet be used to support PRO data collection within the cohort we examined. Comparison with an earlier cohort demonstrates an increase in the number of RCTs planning to use HSD. </jats:sec

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

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

Children’s views on research without prior consent in emergency situations:a UK qualitative study

Objectives We explored children’s views on research without prior consent (RWPC) and sought to identify ways of involving children in research discussions. Design Qualitative interview study. Setting Participants were recruited through a UK children’s hospital and online advertising. Participants 16 children aged 7–15 years with a diagnosis of asthma (n=14) or anaphylaxis (n=2) with recent (<12 months) experience of emergency care. Results Children were keen to be included in medical research and viewed RWPC as acceptable in emergency situations if trial interventions were judged safe. Children trusted that doctors would know about their trial participation and act in their best interests. All felt that children should be informed about the research following their recovery and involved in discussions with a clinician or their parent(s) about the use of data already collected as well as continued participation in the trial (if applicable). Participants suggested methods to inform children about their trial participation including an animation. Conclusions Children supported, and were keen to be involved in, clinical trials in emergency situations. We present guidance and an animation that practitioners and parents might use to involve children in trial discussions following their recovery

Trial Steering Committees in randomised controlled trials: A survey of registered clinical trials units to establish current practice and experiences

Background: The Medical Research Council Guidelines for Good Clinical Practice outlines a three-committee trial oversight structure – the day-to-day Trial Management Group, the Data Monitoring Committee and the Trial Steering Committee. In this model, the Trial Steering Committee is the executive committee that oversees the trial and considers the recommendations from the Data Monitoring Committee. There is yet to be in-depth consideration establishing the Trial Steering Committee’s role and functionality. Methods: A survey to establish Trial Steering Committee’s current practices, role and the use and opinion on the Medical Research Council guidelines was undertaken within UK Clinical Research Collaborative registered Clinical Trials Units. Results: Completed surveys were obtained from 38 of 47 fully and partially registered Units. Individual items in the survey were analysed and reported spanning current Trial Steering Committee practices including its role, requirement and experience required for membership; methods to identify members; and meeting frequency. Terms (a document describing the committee’s remit, objectives and functionality) were obtained and analysed from 21 of 33 Units with documents in place at their Unit. A total of 20 responders suggested aspects of the current Medical Research Council Guidelines that need improvement. Conclusion: We present the first survey reporting on practices within UK Clinical Research Collaborative registered Clinical Trials Units on the experience and remits of Trial Steering Committees. We have identified a widespread adoption of Medical Research Council Guidelines for Trial Steering Committees in the United Kingdom, but limitations in this existing provision have been identified that need to be addressed. </jats:sec

Antibiotic or silver versus standard ventriculoperitoneal shunts (BASICS): a multi-centre, single-blinded, randomised trial and economic evaluation

Background Insertion of a ventriculoperitoneal shunt for hydrocephalus is one of the commonest neurosurgical procedures worldwide. Infection of the implanted shunt affects up to 15% of these patients, resulting in prolonged hospital treatment, multiple surgeries, and reduced cognition and quality of life. Our aim was to determine the clinical and cost-effectiveness of antibiotic (rifampicin and clindamycin) or silver shunts compared with standard shunts at reducing infection. Methods In this parallel, multicentre, single-blind, randomised controlled trial, we included patients with hydrocephalus of any aetiology undergoing insertion of their first ventriculoperitoneal shunt irrespective of age at 21 regional adult and paediatric neurosurgery centres in the UK and Ireland. Patients were randomly assigned (1:1:1 in random permuted blocks of three or six) to receive standard shunts (standard shunt group), antibiotic-impregnated (0·15% clindamycin and 0·054% rifampicin; antibiotic shunt group), or silver-impregnated shunts (silver shunt group) through a randomisation sequence generated by an independent statistician. All patients and investigators who recorded and analysed the data were masked for group assignment, which was only disclosed to the neurosurgical staff at the time of operation. Participants receiving a shunt without evidence of infection at the time of insertion were followed up for at least 6 months and a maximum of 2 years. The primary outcome was time to shunt failure due the infection and was analysed with Fine and Gray survival regression models for competing risk by intention to treat. This trial is registered with ISRCTN 49474281. Findings Between June 26, 2013, and Oct 9, 2017, we assessed 3505 patients, of whom 1605 aged up to 91 years were randomly assigned to receive either a standard shunt (n=536), an antibiotic-impregnated shunt (n=538), or a silver shunt (n=531). 1594 had a shunt inserted without evidence of infection at the time of insertion (533 in the standard shunt group, 535 in the antibiotic shunt group, and 526 in the silver shunt group) and were followed up for a median of 22 months (IQR 10–24; 53 withdrew from follow-up). 32 (6%) of 533 evaluable patients in the standard shunt group had a shunt revision for infection, compared with 12 (2%) of 535 evaluable patients in the antibiotic shunt group (cause-specific hazard ratio [csHR] 0·38, 97·5% CI 0·18–0·80, p=0·0038) and 31 (6%) of 526 patients in the silver shunt group (0·99, 0·56–1·74, p=0·96). 135 (25%) patients in the standard shunt group, 127 (23%) in the antibiotic shunt group, and 134 (36%) in the silver shunt group had adverse events, which were not life-threatening and were mostly related to valve or catheter function. Interpretation The BASICS trial provides evidence to support the adoption of antibiotic shunts in UK patients who are having their first ventriculoperitoneal shunt insertion. This practice will benefit patients of all ages by reducing the risk and harm of shunt infection. Funding UK National Institute for Health Research Health Technology Assessment programme

What Parents of Children Who Have Received Emergency Care Think about Deferring Consent in Randomised Trials of Emergency Treatments: Postal Survey

OBJECTIVE: To investigate parents' views about deferred consent to inform management of trial disclosure after a child's death. METHODS: A postal questionnaire survey was sent to members of the Meningitis Research Foundation UK charity, whose child had suffered from bacterial meningitis or meningococcal septicaemia within the previous 5 years. Main outcome measures were acceptability of deferred consent; timing of requesting consent; and the management of disclosure of the trial after a child's death. RESULTS: 220 families were sent questionnaires of whom 63 (29%) were bereaved. 68 families responded (31%), of whom 19 (28%) were bereaved. The majority (67%) was willing for their child to be involved in the trial without the trial being explained to them beforehand; 70% wanted to be informed about the trial as soon as their child's condition had stabilised. In the event of a child's death before the trial could be discussed the majority of bereaved parents (66% 12/18) anticipated wanting to be told about the trial at some time. This compared with 37% (18/49) of non-bereaved families (p = 0.06). Parents' free text responses indicated that the word 'trial' held strongly negative connotations. A few parents regarded gaps in the evidence base about emergency treatments as indicating staff lacked expertise to care for a critically ill child. Bereaved parents' free text responses indicated the importance of individualised management of disclosure about a trial following a child's death. DISCUSSION: Deferred consent is acceptable to the majority of respondents. Parents whose children had recovered differed in their views compared to bereaved parents. Most bereaved parents would want to be informed about the trial in the aftermath of a child's death, although a minority strongly opposed such disclosure. Distinction should be drawn between the views of bereaved and non-bereaved parents when considering the acceptability of different consent processes

A cohort examination to establish reporting of the remit and function of Trial Steering Committees in randomised controlled trials

BACKGROUND: The DAMOCLES project established a widely used Data Monitoring Committee (DMC) Charter for randomised controlled trials (RCTs). Typically, within the UK, the DMC is advisory and recommends to another executive body; the Trial Steering Committee (TSC). Despite the executive role of the TSC, the CONSORT Statement does not explicitly require reporting of TSC activity, although is included as an example of good reporting. A lack of guidance on TSC reporting can impact transparency of trial oversight, ultimately leading to a misunderstanding regarding role and, subsequently, further variation in practice. This review aimed to establish reporting practice of TSC involvement in RCTs, and thus make recommendations for reporting. METHODS: A cohort examination identifying reporting practice was undertaken. The cohort comprised RCTs published in three leading medical journals (the British Medical Journal, The Lancet and the New England Journal of Medicine) within 6 months in 2012 and the full NIHR HTA Monograph series. Details of TSC constitution and impact were extracted from main publications and published supplements. RESULTS: Of 415 publications, 264 were eligible. These were typical in terms of trial design. Variations in reporting between journals and monographs was notable. TSC presence was identified in approximately half of trials (n = 144), of which 109 worked alongside a DMC. No publications justified not convening a TSC. When reported, the role of the committee and examples of impact in design, conduct and analysis were summarised. CONCLUSIONS: We present the first review of reporting TSC activity in the published academic literature. An absence of reporting standards with regards to TSC constitution, activity and impact on trial conduct was identified which can influence transparency of reporting trial oversight. Consistent reporting is vital for the benefits and impact of the TSC role to be understood to support adoption of this oversight structure and reduce global variations in practice