Using behavioral science to increase core outcome set use in trials.

OBJECTIVES: Core outcome sets (COS) are agreed sets of outcomes for use in clinical trials, which can increase standardization and reduce heterogeneity of outcomes in research. Using a COS, or not, is a behavior that can potentially be increased using behavioral strategies. The aim of this study was to identify behavioral intervention components to potentially increase use of COS in trials. METHODS: This project was informed by the Behavior Change Wheel framework. Two reviewers extracted barriers and facilitators to COS use from four recently published studies examining COS use in trials. Barriers and facilitators were coded to the Capability, Opportunity, Motivation-Behavior (COM-B) model, which forms part of the Behavior Change Wheel. COM-B findings were mapped to intervention functions by two reviewers, and then mapped to behavior change techniques (BCTs). Full-team Affordability, Practicability, Effectiveness/Cost-effectiveness, Acceptability, Side effects/Safety, Equity ratings were used to reach consensus on intervention functions and BCTs. BCTs were operationalized using examples of tangible potential applications and were categorized based on similarity. RESULTS: Barriers and facilitators were identified for all capability, opportunity and motivation aspects of the COM-B model. Five intervention functions (education, training, enablement, persuasion, and modeling) and 15 BCTs were identified. Thirty-six BCT examples were developed, including providing information on benefits of COS for health research, and information choosing COS. BCT examples are categorized by approaches related to "workshops," "guidance," "audio/visual resources," and "other resources." CONCLUSION: Study findings represent diverse ways to potentially increase COS use in trials. Future work is needed to examine effects of these behavioral intervention components on COS use. If effective, increased use of COS can improve outcome reporting and minimize outcome heterogeneity and research waste.

Enhanced Stress Resilience Training for UK Surgical Trainees; Effect and Evolution Evaluated.

INTRODUCTION: Core Surgical Training (CST) programs are associated with high burnout. This study aimed to assess the influence of Enhanced Stress Resilience Training (ESRT) over a 2-year period in a single UK Statutory Education Body. METHOD: CSTs participated in 5-weeks of formal ESRT to address work stressors. The primary outcome measure was career progression related to curriculum metrics and National Training Number (NTN) appointment. Secondary measures related to burnout using validated psychological inventories. RESULTS: Of 42 CSTs, 13 engaged fully with ESRT (31.0%; male 8, female 5, median age 28 year.), 11 engaged partially, and 18 did not. ESRT engagement was associated with better NTN appointment (ESRT 8/13 (61.5%) vs. not 1/18 (5.6%), p = 0.025), less burnout [aMBI; mean 5.14 (SD ± 2.35) vs. 3.14 (±2.25), F 6.637, p = 0.002, ηp2=0.167], less stress [PSS-10; 19.22 (±5.91) vs. 15.79 (±5.47), F 8.740, p < 0.001, ηp2=0.200], but more mindfulness [CAMS-R; 19.22 (±5.91) vs. 20.57 (±2.93), F 3.201, p = 0.047, ηp2=0.084]. On multivariable analysis, Improving Surgical Training (run-through CST) program (OR 5.2 (95% CI 1.42-28.41, p = 0.022), MRCS pass (OR 17.128 (95% CI 1.48-197.11, p = 0.023) and ESRT engagement (OR 13.249, 95% CI 2.08-84.58, p = 0.006) were independently associated with NTN success. DISCUSSION: ESRT was associated with less stress and burnout, better mindfulness, and most importantly 13-fold better career progression.

Reminding Peer Reviewers of Reporting Guideline Items to Improve Completeness in Published Articles: Primary Results of 2 Randomized Trials.

Importance: Numerous studies have shown that adherence to reporting guidelines is suboptimal. Objective: To evaluate whether asking peer reviewers to check if specific reporting guideline items were adequately reported would improve adherence to reporting guidelines in published articles. Design, Setting, and Participants: Two parallel-group, superiority randomized trials were performed using manuscripts submitted to 7 biomedical journals (5 from the BMJ Publishing Group and 2 from the Public Library of Science) as the unit of randomization, with peer reviewers allocated to the intervention or control group. Interventions: The first trial (CONSORT-PR) focused on manuscripts that presented randomized clinical trial (RCT) results and reported following the Consolidated Standards of Reporting Trials (CONSORT) guideline, and the second trial (SPIRIT-PR) focused on manuscripts that presented RCT protocols and reported following the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline. The CONSORT-PR trial included manuscripts that described RCT primary results (submitted July 2019 to July 2021). The SPIRIT-PR trial included manuscripts that contained RCT protocols (submitted June 2020 to May 2021). Manuscripts in both trials were randomized (1:1) to the intervention or control group; the control group received usual journal practice. In the intervention group of both trials, peer reviewers received an email from the journal that asked them to check whether the 10 most important and poorly reported CONSORT (for CONSORT-PR) or SPIRIT (for SPIRIT-PR) items were adequately reported in the manuscript. Peer reviewers and authors were not informed of the purpose of the study, and outcome assessors were blinded. Main Outcomes and Measures: The difference in the mean proportion of adequately reported 10 CONSORT or SPIRIT items between the intervention and control groups in published articles. Results: In the CONSORT-PR trial, 510 manuscripts were randomized. Of those, 243 were published (122 in the intervention group and 121 in the control group). A mean proportion of 69.3% (95% CI, 66.0%-72.7%) of the 10 CONSORT items were adequately reported in the intervention group and 66.6% (95% CI, 62.5%-70.7%) in the control group (mean difference, 2.7%; 95% CI, -2.6% to 8.0%). In the SPIRIT-PR trial, of the 244 randomized manuscripts, 178 were published (90 in the intervention group and 88 in the control group). A mean proportion of 46.1% (95% CI, 41.8%-50.4%) of the 10 SPIRIT items were adequately reported in the intervention group and 45.6% (95% CI, 41.7% to 49.4%) in the control group (mean difference, 0.5%; 95% CI, -5.2% to 6.3%). Conclusions and Relevance: These 2 randomized trials found that it was not useful to implement the tested intervention to increase reporting completeness in published articles. Other interventions should be assessed and considered in the future. Trial Registration: ClinicalTrials.gov Identifiers: NCT05820971 (CONSORT-PR) and NCT05820984 (SPIRIT-PR).

A retrospective cohort study of differential attainment, COVID and chaos: taking the difference out of a terrible trinity.

BACKGROUND: This study aimed to evaluate core surgical training (CST) differential attainment related to coronavirus disease 2019 (COVID-19), gender and ethnicity. The hypothesis was that COVID-19 adversely influenced CST outcomes. METHODS: A retrospective cohort study of 271 anonymised CST records was undertaken at a UK Statutory Education Body. Primary effect measures were Annual Review of Competency Progression Outcome (ARCPO), Membership of the Royal College of Surgeons (MRCS) examination pass and Higher Surgical Training National Training Number (NTN) appointment. Data were collected prospectively at ARCP and analysed with non-parametric statistical methods in SPSS. RESULTS: CSTs numbering 138 completed training pre-COVID and 133 peri-COVID. ARCPO 1, 2 and 6 were 71.9% pre-COVID versus 74.4% peri-COVID ( P =0.844). MRCS pass rates were 69.6% pre-COVID versus 71.1% peri-COVID ( P =0.968), but NTN appointment rates diminished (pre-COVID 47.4% vs. peri-COVID 36.9%, P =0.324); none of the above varied by gender or ethnicity. Multivariable analyses by three models revealed: ARCPO was associated with gender [m:f 1:0.87, odds ratio (OR) 0.53, P =0.043] and CST theme (Plastics vs. General OR 16.82, P =0.007); MRCS pass with theme (Plastics vs. General OR 8.97, P =0.004); NTN with the Improving Surgical Training run-through programme (OR 5.00, P <0.001). Programme retention improved peri-COVID (OR 0.20, P =0.014) with pan University Hospital rotations performing better than Mixed or District General-only rotations (OR 6.63, P =0.018). CONCLUSION: Differential attainment profiles varied 17-fold, yet COVID-19 did not influence ARCPO or MRCS pass rates. NTN appointment fell by one-fifth peri-COVID, but overall training outcome metrics remained robust despite the existential threat.

Accuracy of diagnostic tests in cardiac injury after blunt chest trauma: a systematic review and meta-analysis.

INTRODUCTION: The diagnosis of cardiac contusion, caused by blunt chest trauma, remains a challenge due to the non-specific symptoms it causes and the lack of ideal tests to diagnose myocardial damage. A cardiac contusion can be life-threatening if not diagnosed and treated promptly. Several diagnostic tests have been used to evaluate the risk of cardiac complications, but the challenge of identifying patients with contusions nevertheless remains. AIM OF THE STUDY: To evaluate the accuracy of diagnostic tests for detecting blunt cardiac injury (BCI) and its complications, in patients with severe chest injuries, who are assessed in an emergency department or by any front-line emergency physician. METHODS: A targeted search strategy was performed using Ovid MEDLINE and Embase databases from 1993 up to October 2022. Data on at least one of the following diagnostic tests: electrocardiogram (ECG), serum creatinine phosphokinase-MB level (CPK-MB), echocardiography (Echo), Cardiac troponin I (cTnI) or Cardiac troponin T (cTnT). Diagnostic tests for cardiac contusion were evaluated for their accuracy in meta-analysis. Heterogeneity was assessed using the I2 and the QUADAS-2 tool was used to assess bias of the studies. RESULTS: This systematic review yielded 51 studies (n = 5,359). The weighted mean incidence of myocardial injuries after sustaining a blunt force trauma stood at 18.3% of cases. Overall weighted mean mortality among patients with blunt cardiac injury was 7.6% (1.4-36.4%). Initial ECG, cTnI, cTnT and transthoracic echocardiography TTE all showed high specificity (> 80%), but lower sensitivity (< 70%). TEE had a specificity of 72.1% (range 35.8-98.2%) and sensitivity of 86.7% (range 40-99.2%) in diagnosing cardiac contusion. CK-MB had the lowest diagnostic odds ratio of 3.598 (95% CI: 1.832-7.068). Normal ECG accompanied by normal cTnI showed a high sensitivity of 85% in ruling out cardiac injuries. CONCLUSION: Emergency physicians face great challenges in diagnosing cardiac injuries in patients following blunt trauma. In the majority of cases, joint use of ECG and cTnI was a pragmatic and cost-effective approach to rule out cardiac injuries. In addition, TEE may be highly accurate in identifying cardiac injuries in suspected cases.

Differential attainment in higher surgical training: scoping pan-specialty spectra.

INTRODUCTION: This study aimed to evaluate differential attainment during higher surgical training (HST; all specialties) related to three ethnic cohorts: White UK (WUKG), Black and Minority Ethnic UK Graduates (BMEUKG), and International Medical Graduates (IMG). METHOD: Anonymised records of 266 HSTs (126 WUKG, 65 BMEUKG, 75 IMG; 7 years) in a single UK Statutory Education Body were examined. Primary effect measures were Annual Record of Competency Progression Outcome (ARCPO) and Fellowship of the Royal College of Surgeons (FRCS) pass. RESULTS: ARCPOs related to ethnicity and specialty were similar with the exception of general surgery (GS) trainees, four of whom received ARCPO 4 (GS 4.9% (75% BME; p=0.025) vs all other 0%). ARCPO 3 was commoner in women (22/76, (28.9%) than men 27/190 (14.2%), OR 2.46, p=0.006). FRCS pass rates (WUKG vs BMEUKG vs IMG) were 76.9%, 52.9% and 53.9% respectively (p=0.064) but unrelated to gender (M 70.4% vs F 64.3%). On multivariable analyses: ARCPO 3 was associated with Female gender and Maternity Leave (OR 8.05, p=0.001); FRCS pass with ethnicity (OR 0.21, p=0.028) and Hirsch Indices of ≥5 (OR 11.17, p=0.001). CONCLUSION: Differential attainment was plain with BMEUKG FRCS performance almost a third poorer than WUKG, and women twofold more likely to receive adverse ARCPOs, with return from statutory leave independently associated with training extension. Focused counter measures targeted at non-operative technical skills (including academic reach), Keeping in Touch, Return to Work, and re-induction programmed support are urgently needed for trainees at risk.

Recommendations for progression criteria during external randomised pilot trial design, conduct, analysis and reporting.

BACKGROUND: External randomised pilot trials aim to assess whether a future definitive Randomised Controlled Trial (RCT) is feasible. Prespecified progression criteria help guide the interpretation of pilot trial findings to decide whether, and how, a definitive RCT should be conducted. This commentary presents a set of proposed recommendations for progression criteria to guide researchers when (i) designing, (ii) conducting, (iii) analysing and (iv) reporting external randomised pilot trials. METHODS: Recommendations were developed following a mixed methods approach. This involved (i) a methodological review of pilot trial publications, (ii) a cross-sectional study of pilot trial research funding applications, (iii) qualitative interviews with pilot trial researchers and (iv) a survey of corresponding authors of identified pilot trial publications. Initial recommendations were refined following two consultation stakeholder workshops held in July 2022. Recommendations for progression criteria for external randomised pilot trials: i. DESIGN: consider progression criteria from the earliest opportunity; map progression criteria to feasibility objectives; consider quantitative and qualitative interpretations of feasibility; provide justification; develop guidelines rather than rules; seek input from relevant stakeholders. ii. Conduct: regularly monitor pilot trial data against progression criteria. iii. ANALYSIS: avoid considering each progression criterion in isolation; engage in discussion with relevant stakeholders; consider context and other factors external to the pilot trial; consider feasibility (can we?) and progression (will we?). iv. Reporting: we propose a reporting checklist in relation to progression criteria and recommend reporting in a table format for clarity. CONCLUSION: These recommendations provide a helpful resource for researchers to consider progression criteria at different stages of external randomised pilot trials. We have produced a simple infographic tool to summarise these recommendations for researchers to refer to. Further research is needed to evaluate whether these proposed recommendations should inform future development, or update, of established guidelines for the design, conduct, analysis and reporting of external randomised pilot trials.

Personal protective equipment-induced systemic hypercapnic hypoxaemia: translational implications for impaired cognitive-clinical functional performance.

BACKGROUND: Personal protective equipment (PPE) adversely affects pulmonary gas exchange and may result in systemic hypercapnic hypoxaemia and headache. This study aimed to determine what extent PPE affects cerebral symptoms, global cerebral blood flow, and cognitive functional performance. METHODS: Higher surgical trainees participated in a randomized, repeated-measures, crossover study, completing 60 min of laparoscopic surgical simulation in both standard operating attire and type 3 PPE. Measurements were collected at baseline and after 60 min of simulation. The primary outcome measure was headache. Headache was examined using the validated visual analogue scale (VAS) and Environmental Symptoms Questionnaire C (ESQ-C), global cerebral blood flow with duplex ultrasonography, and visuospatial and executive gross/fine motor function with grooved peg board (GPB) and laparoscopic bead (LSB) board tasks. RESULTS: Thirty-one higher surgical trainees (20 men, 11 women) completed the study. Compared with standard operating attire, PPE increased headache assessment scores (mean(s.d.) VAS score 3.5(5.6) versus 13.0(3.7), P < 0.001; ESQ-C score 1.3(2.0) versus 5.9(5.1), P < 0.001) and was associated with poorer completion times for GPB-D (61.4(12.0) versus 71.1(12.4) s; P = 0.034) and LSB (192.5(66.9) versus 270.7(135.3) s; P = 0.025) tasks. Wearing PPE increased heart rate (82.5(13.6) versus 93.5(13.0) beats/min; P = 0.022) and skin temperature (36.6(0.4) versus 37.1(0.5)°C; P < 0.001), but decreased peripheral oxygen saturation (97.9(0.8) versus 96.8(1.0) per cent; P < 0.001). Female higher surgical trainees exhibited higher peripheral oxygen saturation across all conditions. No differences were observed in global cerebral blood flow as a function of attire, time or sex. CONCLUSION: Despite no marked changes in global cerebral blood flow, type 3 PPE was associated with increased headache scores and cerebral symptoms (VAS and ESQ-C) alongside impaired executive motor function highlighting the clinical implications of PPE-induced impairment for cognitive-clinical performance.

Pilot and feasibility studies: extending the conceptual framework.

In 2016, we published a conceptual framework outlining the conclusions of our work in defining pilot and feasibility studies. Since then, the CONSORT extension to randomised pilot and feasibility trials has been published and there have been further developments in the pilot study landscape. In this paper, we revisit and extend our framework to incorporate the various feasibility pathways open to researchers, which include internal pilot studies. We consider, with examples, when different approaches to feasibility and pilot studies are more effective and efficient, taking into account the pragmatic decisions that may need to be made. The ethical issues involved in pilot studies are discussed. We end with a consideration of the funders' perspective in making difficult resource decisions to include feasibility work and the policy implications of these; throughout, we provide examples of the uncertainties and compromises that researchers have to navigate to make progress in the most efficient way.

The most influential COVID-19 articles: A systematic review.

Background: Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),causative pathogen of coronavirus disease 2019 (COVID-19), has triggered a pandemic with challenges for health care systems around the world. Researchers have studied and published on the subject of SARS-CoV-2 and the disease extensively. What is the significance of articles published, shared and cited in the early stages of such a pandemic? Materials and methods: A systematic literature search in a time frame of 12 months and analysis rating using Principle Component Analysis (PCA) and Multiple Factor Analysis (MFA) were performed. Results: The 100 most cited COVID-19 articles were identified. The majority of these articles were from China (n = 54), followed by United States of America (USA) (n = 21) and United Kingdom (UK) (n = 8). All articles were published in high-ranked, peer-reviewed journals, with research focusing onthe the diagnosis, transmission and therapy of COVID-19. The level of evidence of the 100 most cited COVID-19 articles on average was low. Conclusion: In the early stages of a pandemic, new and innovative research can emerge and be highly cited, regardless of the level of evidence.

Determining external randomised pilot trial feasibility in preparation for a definitive trial: a web-based survey of corresponding authors of external pilot trial publications.

BACKGROUND: External randomised pilot trials aim to determine whether a future definitive randomised controlled trial (RCT) should be conducted, and if so, how. However, not every pilot trial that suggests that a definitive trial will be feasible will progress to a definitive study. In this study, we surveyed corresponding authors of external randomised pilot trial publications to assess pilot trial outcomes in terms of feasibility and progression. METHODS: Web-based surveys were sent to corresponding authors of external randomised pilot trial publications, open for four weeks between January and February 2022. Four surveys were produced depending on whether the corresponding author had published a trial protocol or results publication, and whether progression criteria were reported. Surveys asked whether a future RCT was considered feasible, whether progression criteria were met (if applicable), what other factors informed the assessment of pilot trial feasibility, and whether the pilot trial has progressed to further research. Data was analysed using descriptive statistics and conventional content analysis. RESULTS: 98 of 276 corresponding authors completed the survey (average response rate of 36% across all surveys). Of these, 89 respondents indicated that their trial had completed. Ninety per cent of respondents who were corresponding authors of completed pilot trials stated that their pilot trial was either feasible (42/89, 47%) or feasible with changes to the trial design (38/89, 43%), yet only 66% (59/89) reported the intention to conduct a future definitive trial. Availability of funding for a future definitive trial and changing priorities of the Chief Investigator were the most common barriers to progression identified. Qualitative research findings was the most frequent factor considered both by corresponding authors who reported and who did not report progression criteria when determining trial feasibility. CONCLUSIONS: Just under one quarter (21/89, 24%) of respondents who considered their external randomised pilot trial to be feasible, or feasible with changes, did not intend to conduct a definitive trial highlighting research inefficiency and waste. TRIAL REGISTRATION: Open Science Framework osf.io/d28hr [20 December 2021].

Inclusion of progression criteria in external randomised pilot trials: a cross-sectional study of funding applications submitted to the NIHR Research for Patient Benefit Programme.

BACKGROUND: External randomised pilot trials aim to assess whether a future definitive randomised controlled trial (RCT) is feasible. Pre-specified progression criteria help guide the interpretation of pilot trial findings to decide whether, and how, a definitive trial should be conducted. We aimed to examine how researchers report and plan to assess progression criteria in external pilot trial funding applications submitted to the NIHR Research for Patient Benefit Programme. METHODS: We conducted a cross-sectional study of progression criteria inclusion in Stage 1 (outline) and corresponding Stage 2 (full) funding applications for external randomised external pilot trials submitted to NIHR RfPB between July 2017 and July 2019. RESULTS: Of the 100 Stage 1 outline applications assessed, 95 were eligible for inclusion (of these, 52 were invited to Stage 2 full application; 43 were rejected) and 49/52 were eligible for inclusion at Stage 2 full application (of these, 35 were awarded funding; 14 were rejected). Over half of applications assessed at Stage 1 (48/95, 51%), and 73% of those assessed at Stage 2 (36/49) included progression criteria in their research plans. Progression criteria were most often reported in a stop-go format, often with additional specified factors that should be considered when determining feasibility (Stage 1 33/48, 69%; Stage 2 21/36, 58%). Recruitment and retention were the most frequent indicators of feasibility to inform progression criteria. One-third of applications provided some justification or rationale for their targets (Stage 1 16/48, 33%; Stage 2 12/36, 33%). Funding committee feedback mentioned progression criteria in over 20% of applications (Stage 1 22/95, 23%; Stage 2 11/49, 22%) to either request the addition of progression criteria or provide justification for the criteria stipulated. CONCLUSIONS: Our findings indicate that researchers do not always include progression criteria in external randomised pilot trial applications submitted to research funders. This can result in a lack of transparency in the assessment of randomised pilot trial feasibility. TRIAL REGISTRATION: Open Science Framework osf.io/89ap7, registered 29th June 2021.

The reporting of pilot and feasibility studies in the top dental specialty journals is suboptimal.

BACKGROUND: Pilot and feasibility studies (PAFS) are smaller investigations seeking to assess the feasibility of conducting a larger more definitive study. In late 2016, the CONSORT statement was extended to disseminate good practices for reporting of randomized pilot and feasibility trials. In this quality assurance review, we assessed whether PAFS in the top dental speciality journals adhere to good practices of conduct and reporting, by prioritizing assessment of feasibility and stating pre-defined progression criteria to inform the decision to pursue funding for a larger trial. METHODS: With the help of a librarian, we searched MEDLINE and EMBASE from 2017 to 2020, inclusive, for PAFS in the top 3 journals from each of the 10 dental specialties. We collected data on methodological and general characteristics of the studies, their objectives, and reporting of items recommended in the CONSORT extension. RESULTS: Of the 111 trials included, 51.4% (95% CI 41.7-61.0%) stated some indication of intent to assess feasibility while zero reported progression criteria; 74.8% (95% CI 65.6-82.5%) of trials used the terms "pilot" or "feasibility" in their titles and 82.9% (95% CI 74.6-89.4%) of studies stated there is a need for a future trial, but only 9.0% (95% CI 4.4-15.9%) stated intent to proceed to one. Most of the studies, 53.2% (95% CI 43.4-62.7%), reported hypothesis testing without cautioning readers on the generalizability of the results. Studies that used the terms "pilot" or "feasibility" in their title were less likely to have feasibility objectives, compared to trials that did not, with an odds ratio (OR) of 0.310 (95% CI 0.103-0.930; p = 0.037). Compared to trials that did not conduct hypothesis testing, trials that conducted hypothesis testing were significantly less likely to assess feasibility, among them, trials that cautioned readers on the generalizability of their results had an OR of 0.038 (95% CI 0.005-0.264; p < 0.001) and trials that did not caution readers on the generalizability of their results had an OR of 0.043 (95% CI 0.008-0.238; p = 0.001). CONCLUSION: Many PAFS in dentistry are not conducted with the intent of assessing feasibility, nor do they state progression criteria, and few report intent to proceed to a future trial. Misconceptions about PAFS can lead to them being poorly conducted and reported, which has economic and ethical implications. Research ethics boards, funding agencies, and journals need to raise their standards for the conduct and reporting of PAFS, and resources should be developed to address misconceptions and help guide researchers on the best practices for their conduct and reporting.

Melatonin for pre-medication in children: a systematic review.

BACKGROUND: Melatonin's effectiveness as an anxiolytic medication has been confirmed in adults; however, its efficacy in a paediatric population is unclear. A number of small studies have assessed its use in children as a pre-operative anxiolytic, with conflicting results. METHODS: We undertook a systematic review of pre-operative melatonin use in children. Four databases (MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Web of Science), and ' ClinicalTrials.gov ' were searched for ongoing and completed clinical trials of relevance. Citation tracking reference lists and relevant articles were also accessed. The review was unrestricted by comparator or outcomes. Eleven studies were judged eligible for inclusion. There were high levels of heterogeneity in melatonin administration (in terms of dose and timing). Variable outcomes were reported and included: anxiety; anaesthetic success; analgesia; sedation; post-operative recovery; and safety. Outcomes were not always assessed with the same measures. RESULTS: Evidence to support melatonin's anxiolytic properties in this setting is conflicting. Melatonin was associated with reduced sedative effects, post-operative excitement and improved emergence behaviour, compared to comparator drugs. One study reported the benefit of melatonin use on sleep disturbance at two weeks post-surgery. No adverse safety events were identified to be significantly associated with melatonin, affirming its excellent safety profile. CONCLUSION: Despite potential advantages, including improved emergence behaviour, based on current evidence we cannot confirm whether melatonin is non-inferior to current "usual care" pre-medications. Further consideration of melatonin as an anxiolytic pre-medication in paediatric surgery is needed.

How are progression decisions made following external randomised pilot trials? A qualitative interview study and framework analysis.

BACKGROUND: External randomised pilot trials help researchers decide whether, and how, to do a future definitive randomised trial. The progression criteria are often prespecified to inform the interpretation of pilot trial findings and subsequent progression decision-making. We aimed to explore and understand the perspectives and experiences of key stakeholders when making progression decisions following external pilot trials. METHODS: Thirty-five remote semi-structured interviews with external randomised pilot trial team members including chief investigators, trial managers, statisticians and patient and public involvement (PPI) representatives. Questions focussed on experiences and perceptions of pilot trial progression decisions and whether and how progression criteria informed this decision. Data were analysed using the framework method approach to thematic analysis. Strategies to ensure trustworthiness and rigour were used. RESULTS: Interviews were conducted between December 2020 and July 2021. Six descriptive themes were developed to capture the experiences and perspectives of participants. These were (1) divided opinions on the value and development of progression criteria, (2) (avoiding) the potential for personal interest to influence progression criteria and progression decision-making, (3) stakeholder engagement in setting progression criteria and making progression decisions, (4) lessons learned from doing the pilot trial and their impact on progression criteria applicability, (5) other factors that inform the progression decision and (6) progression of external randomised pilot trials-funding considerations and constraints. These themes were underpinned by an overarching interpretative theme 'a one-size approach to progression does not fit all' to describe the highly nuanced and complex decision-making process that occurs following external randomised pilot trials. The progression criteria are rarely the only consideration informing the decision to progress to future research; unanticipated events, signals of efficacy and continuity of the research team are other factors that researchers consider. CONCLUSIONS: One size does not fit all when it comes to the progression criteria and pilot trial progression. The progression criteria are only one of many considerations researchers have when deciding whether a pilot trial is feasible. External pilot trial progression is not guaranteed even when a pilot trial is considered feasible (based on the progression criteria and/or other considerations), indicating inefficiency and potential research waste. TRIAL REGISTRATION: Open Science Framework osf.io/5N2KZ.

Using behavioural science to enhance use of core outcome sets in trials: protocol.

Background: Core outcome sets (COS) represent agreed-upon sets of outcomes, which are the minimum that should be measured and reported in all trials in specific health areas. Use of COS can reduce outcome heterogeneity, selective outcome reporting, and research waste, and can facilitate evidence syntheses. Despite benefits of using COS, current use of COS in trials is low. COS use can be understood as a behaviour, in that it is something trialists do, or not do, adequately. The aim of this study is to identify strategies, informed by behaviour change theory, to increase COS use in trials. Methods: The project will be conducted in two stages, informed by the behaviour change wheel (BCW). The BCW is a theoretically based framework that can be used to classify, identify, and develop behaviour change strategies. In Stage 1, barriers and enablers to COS use will be extracted from published studies that examined trialist's use of COS. Barriers and facilitators will be mapped to the components of COM-B model (capability, opportunity, and motivation), which forms part of the BCW framework. Stage 2 will build on Stage 1 findings to identify and select intervention functions and behaviour change techniques to enhance COS use in trials. Discussion: The findings of this study will provide an understanding of the behavioural factors that influence COS use in trials and what strategies might be used to target these factors to increase COS use in trials.