A concept analysis of ‘trial recruitment’ using the hybrid model

Funding Information: Health Research Board [TMRN-2017-2].Peer reviewedPublisher PD

The development and acceptability of an educational and training intervention for recruiters to neonatal trials : the TRAIN project

Peer reviewedPublisher PD

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

Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49). Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens

Development of an online resource for recruitment research in clinical trials to organise and map current literature

Medical Research Council (MRC) Network of Hubs for Trials Methodology Research (MR/L004933/1– B2).Peer reviewedPublisher PD

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

The cost of diagnostic uncertainty: a prospective economic analysis of febrile children attending an NHS emergency department.

BACKGROUND: Paediatric fever is a common cause of emergency department (ED) attendance. A lack of prompt and definitive diagnostics makes it difficult to distinguish viral from potentially life-threatening bacterial causes, necessitating a cautious approach. This may result in extended periods of observation, additional radiography, and the precautionary use of antibiotics (ABs) prior to evidence of bacterial foci. This study examines resource use, service costs, and health outcomes. METHODS: We studied an all-year prospective, comprehensive, and representative cohort of 6518 febrile children (aged < 16 years), attending Alder Hey Children's Hospital, an NHS-affiliated paediatric care provider in the North West of England, over a 1-year period. Performing a time-driven and activity-based micro-costing, we estimated the economic impact of managing paediatric febrile illness, with focus on nurse/clinician time, investigations, radiography, and inpatient stay. Using bootstrapped generalised linear modelling (GLM, gamma, log), we identified the patient and healthcare provider characteristics associated with increased resource use, applying retrospective case-note identification to determine rates of potentially avoidable AB prescribing. RESULTS: Infants aged less than 3 months incurred significantly higher resource use than any other age group, at £1000.28 [95% CI £82.39-£2993.37] per child, (p < 0.001), while lesser experienced doctors exhibited 3.2-fold [95% CI 2.0-5.1-fold] higher resource use than consultants (p < 0.001). Approximately 32.4% of febrile children received antibiotics, and 7.1% were diagnosed with bacterial infections. Children with viral illnesses for whom antibiotic prescription was potentially avoidable incurred 9.9-fold [95% CI 6.5-13.2-fold] cost increases compared to those not receiving antibiotics, equal to an additional £1352.10 per child, predominantly resulting from a 53.9-h increase in observation and inpatient stay (57.1 vs. 3.2 h). Bootstrapped GLM suggested that infants aged below 3 months and those prompting a respiratory rate 'red flag', treatment by lesser experienced doctors, and Manchester Triage System (MTS) yellow or higher were statistically significant predictors of higher resource use in 100% of bootstrap simulations. CONCLUSION: The economic impact of diagnostic uncertainty when managing paediatric febrile illness is significant, and the precautionary use of antibiotics is strongly associated with increased costs. The use of ED resources is highest among infants (aged less than 3 months) and those infants managed by lesser experienced doctors, independent of clinical severity. Diagnostic advances which could increase confidence to withhold antibiotics may yield considerable efficiency gains in these groups, where the perceived risks of failing to identify potentially life-threatening bacterial infections are greatest

Developing an online, searchable database to systematically map and organise current literature on retention research (ORRCA2)

Background: Addressing recruitment and retention challenges in trials is a key priority for methods research, but navigating the literature is difficult and time-consuming. In 2016, ORRCA (www.orrca.org.uk) launched a free, searchable database of recruitment research that has been widely accessed and used to support the update of systematic reviews and the selection of recruitment strategies for clinical trials. ORRCA2 aims to create a similar database to map the growing volume and importance of retention research.  Methods: Searches of Medline (Ovid), CINAHL, PsycINFO, Scopus, Web of Science Core Collection and the Cochrane Library, restricted to English language and publications up to the end of 2017. Hand searches of key systematic reviews were undertaken and randomised evaluations of recruitment interventions within the ORRCA database on 1 October 2020 were also reviewed for any secondary retention outcomes. Records were screened by title and abstract before obtaining the full text of potentially relevant articles. Studies reporting or evaluating strategies, methods and study designs to improve retention within healthcare research were eligible. Case reports describing retention challenges or successes and studies evaluating participant reported reasons for withdrawal or losses were also included. Studies assessing adherence to treatments, attendance at appointments outside of research and statistical analysis methods for missing data were excluded. Eligible articles were categorised into one of the following evidence types: randomised evaluations, non-randomised evaluations, application of retention strategies without evaluation and observations of factors affecting retention. Articles were also mapped against a retention domain framework. Additional data were extracted on research outcomes, methods and host study context.  Results: Of the 72,904 abstracts screened, 4,364 full texts were obtained, and 1,167 articles were eligible. Of these, 165 (14%) were randomised evaluations, 99 (8%) non-randomised evaluations, 319 (27%) strategies without evaluation and 584 (50%) observations of factors affecting retention. Eighty-four percent (n = 979) of studies assessed the numbers of participants retained, 27% (n = 317) assessed demographic differences between retained and lost participants, while only 4% (n = 44) assessed the cost of retention strategies. The most frequently reported domains within the 165 studies categorised as ‘randomised evaluations of retention strategies’ were participant monetary incentives (32%), participant reminders and prompts (30%), questionnaire design (30%) and data collection location and method (26%).  Conclusion: ORRCA2 builds on the success of ORRCA extending the database to organise the growing volume of retention research. Less than 15% of articles were randomised evaluations of retention strategies. Mapping of the literature highlights several areas for future research such as the role of research sites, clinical staff and study design in enhancing retention. Future studies should also include cost–benefit analysis of retention strategies