Child and adolescent mental well-being intervention programme: A systematic review of randomised controlled trials.

Background: There has been an increasing awareness and recognition of mental well-being as one of the main outcome measures in national mental health policy and service provision in recent years. Many systemic reviews on intervention programmes for mental health or general well-being in young people have been conducted; however, these reviews were not mental well-being specific. Objective: This study aims to examine the effectiveness of child and adolescent mental well-being intervention programmes and to identify the approach of effective intervention by reviewing the available Randomised Controlled Trials. Methods: This systematic review study followed the PRISMA guidelines for systematic reviews ensuring a methodical and structured approach for the literature search and the subsequent review processes. The systematic literature search utilised major medical and health databases. Covidence, an online application for conducting systematic reviews, was used to assemble the titles, abstracts and full articles retrieved from the initial literature search. To examine the quality of the included trials for determining the strength of the evidence provided, the JBI Critical Appraisal Tool for Randomised Controlled Trial was used. Results: There were 34 studies identified after an extensive search of the literature following the PRISMA guidelines. Seven (7) fulfilled all selection criteria and provided information on the effect of an intervention programme on mental well-being in adolescence. Data were extracted and analysed systematically with key information summarised. The results suggested that two (2) programmes demonstrated significant intervention effects, but with a small effect size. The quality of these trials was also assessed using the JBI Critical Appraisal Tool for Randomised Controlled Trials and identified some methodological issues. Conclusion: In conclusion, activity-based and psychoeducation are shown to be potentially effective approaches for future programme development. More research on a well-designed programme is urgently needed, particularly in developing countries, to provide good evidence in supporting the mental health policy through the enhancement of mental well-being in young people.

Statistical analyses of ordinal outcomes in randomised controlled trials: protocol for a scoping review.

INTRODUCTION: Randomised controlled trials (RCTs) aim to assess the effect of one (or more) unproven health interventions relative to other reference interventions. RCTs sometimes use an ordinal outcome, which is an endpoint that comprises of multiple, monotonically ordered categories that are not necessarily separated by a quantifiable distance. Ordinal outcomes are appealing in clinical settings as specific disease states can represent meaningful categories that may be of clinical importance to researchers. Ordinal outcomes can also retain information and increase statistical power compared to dichotomised outcomes and can allow multiple clinical outcomes to be comprised in a single endpoint. Target parameters for ordinal outcomes in RCTs may vary depending on the nature of the research question, the modelling assumptions and the expertise of the data analyst. The aim of this scoping review is to systematically describe the use of ordinal outcomes in contemporary RCTs. Specifically, we aim to: [Formula: see text] Identify which target parameters are of interest in trials that use an ordinal outcome, and whether these parameters are explicitly defined. [Formula: see text] Describe how ordinal outcomes are analysed in RCTs to estimate a treatment effect. [Formula: see text] Describe whether RCTs that use an ordinal outcome adequately report key methodological aspects specific to the analysis of the ordinal outcome. Results from this review will outline the current state of practice of the use of ordinal outcomes in RCTs. Ways to improve the analysis and reporting of ordinal outcomes in RCTs will be discussed. METHODS AND ANALYSIS: We will review RCTs that are published in the top four medical journals (British Medical Journal, New England Journal of Medicine, The Lancet and the Journal of the American Medical Association) between 1 January 2012 and 31 July 2022 that use an ordinal outcome as either a primary or a secondary outcome. The review will identify articles through a PubMed-specific search strategy. Our review will adhere to guidelines for scoping reviews as described in the PRISMA-ScR checklist. The study characteristics and details of the study design and analysis, including the target parameter(s) and statistical methods used to analyse the ordinal outcome, will be extracted from eligible studies. The screening, review and data extraction will be conducted using Covidence, a web-based tool for managing systematic reviews. The data will be summarised using descriptive statistics.

A randomised controlled trial (RCT) exploring the impact of a photography intervention on wellbeing and posttraumatic growth during the COVID-19 pandemic.

BACKGROUND: Emerging evidence points to rising levels of psychological distress resulting from the COVID-19 pandemic. There is a need for self-administered, low-cost, and accessible interventions that facilitate wellbeing and growth. METHODS: This study used a randomised controlled trial (RCT) design to investigate the effects of a two-week positivity-oriented photography intervention on wellbeing and posttraumatic growth in comparison to a control group. Participants were adults between the ages of 21 and 80 living in the UK recruited between May and August 2020 (n = 109). RESULTS: After adjusting for baseline wellbeing, both wellbeing and PTG were significantly higher in the intervention group compared to the control group following intervention completion, with this effect remaining similar at one-month follow-up. CONCLUSIONS: The study offers preliminary evidence that a brief self-administered photography intervention could hold therapeutic value.

Patient and health practitioner views and experiences of a cancer trial before and during COVID-19: qualitative study.

BACKGROUND: Understanding patient and health practitioner perspectives on clinical trials can inform opportunities to enhance trial conduct and design, and therefore patient experience. Patients with haematological cancers have faced additional risk and uncertainty during the pandemic but it is unclear how they and practitioners have experienced cancer trials during this period. In the context of a haemato-oncology trial (PETReA), we compared patient and practitioner views and experiences of PETReA before and during COVID-19. METHODS: Qualitative study embedded within PETReA. Semi-structured interviews (N=41) with patients and practitioners from 16 NHS sites before (n=17) and during the first wave of COVID-19 (n=24). Analysis drew on the framework approach. RESULTS: Practitioners acknowledged the need for the trial to continue during the pandemic but their treatment preferences altered, becoming more pronounced for patients who had a favourable response to induction treatment, while staying unchanged for patients with a less favourable response. Practitioners commented that COVID-19 meant the evidence base for the trial arms was lacking or mixed, but that it likely increased the risks of maintenance treatment for patients with a favourable response to induction treatment. While only one participant interviewed withdrew from PETReA during the pandemic, others said they would consider withdrawing if information that they were at increased risk of severe illness from COVID-19 became available. During COVID-19, patients described less frequent contact with the trial team, which left some feeling less clear about their trial pathway. However, several described having in-depth, collaborative discussions with practitioners about the risks and benefits of randomisation in the context of COVID-19. Patients valued these discussions and were reassured by the emphasis practitioners placed on patients being free to withdraw if circumstances changed, and this helped patients feel comfortable about continuing in PETReA. CONCLUSIONS: The findings point to ways trial communication can support patients to feel comfortable about continuing in a trial during uncertain times, including adopting a more in-depth, collaborative exploration of the risks and benefits of trial arms with patients and emphasising voluntariness. The results are relevant to trialists recruiting patients who are clinically extremely vulnerable or are at increased risk of poor COVID-19 outcomes despite being vaccinated.

Unpacking the 'black box of horrendousness': a qualitative exploration of the barriers and facilitators to conducting trials involving adults lacking capacity to consent.

BACKGROUND: Trials involving adults who lack capacity to consent encounter a range of ethical and methodological challenges, resulting in these populations frequently being excluded from research. Currently, there is little evidence regarding the nature and extent of these challenges, nor strategies to improve the design and conduct of such trials. This qualitative study explored researchers' and healthcare professionals' experiences of the barriers and facilitators to conducting trials involving adults lacking capacity to consent. METHODS: Semi-structured interviews were conducted remotely with 26 researchers and healthcare professionals with experience in a range of roles, trial populations and settings across the UK. Data were analysed using thematic analysis. RESULTS: A number of inter-related barriers and facilitators were identified and mapped against key trial processes including during trial design decisions, navigating ethical approval, assessing capacity, identifying and involving alternative decision-makers and when revisiting consent. Three themes were identified: (1) the perceived and actual complexity of trials involving adults lacking capacity, (2) importance of having access to appropriate support and resources and (3) need for building greater knowledge and expertise to support future trials. Barriers to trials included the complexity of the legal frameworks, the role of gatekeepers, a lack of access to expertise and training, and the resource-intensive nature of these trials. The ability to conduct trials was facilitated by having prior experience with these populations, effective communication between research teams, public involvement contributions, and the availability of additional data to inform the trial. Participants also identified a range of context-specific recruitment issues and highlighted the importance of 'designing in' flexibility and the use of adaptive strategies which were especially important for trials during the COVID-19 pandemic. Participants identified a need for better training and support. CONCLUSIONS: Researchers encountered a number of barriers, including both generic and context or population-specific challenges, which may be reinforced by wider factors such as resource limitations and knowledge deficits. Greater access to expertise and training, and the development of supportive interventions and tailored guidance, is urgently needed in order to build research capacity in this area and facilitate the successful delivery of trials involving this under-served population.

Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence.

Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia and sepsis appears to decrease the severity of the disease and potentially improve survival rate. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes pneumonia, sepsis and acute respiratory distress syndrome (ARDS) in severe cases, and is referred to as coronavirus disease 2019 (COVID-19). Patients with COVID-19 infection also appear to have depleted vitamin C status and require additional supplementation of vitamin C during the acute phase of the disease. To date there have been 12 vitamin C and COVID-19 trials published, including five randomised controlled trials (RCTs) and seven retrospective cohort studies. The current level of evidence from the RCTs suggests that intravenous vitamin C intervention may improve oxygenation parameters, reduce inflammatory markers, decrease days in hospital and reduce mortality, particularly in the more severely ill patients. High doses of oral vitamin C supplementation may also improve the rate of recovery in less severe cases. No adverse events have been reported in published vitamin C clinical trials in COVID-19 patients. Upcoming findings from larger RCTs will provide additional evidence on vitamin supplementation in COVID-19 patients.

Making trials part of good clinical care: lessons from the RECOVERY trial.

When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.

The Pediatric Emergency Research Network (PERN): A decade of global research cooperation in paediatric emergency care.

OBJECTIVES: The Pediatric Emergency Research Network (PERN) was launched in 2009 with the intent for existing national and regional research networks in paediatric emergency care to organise globally for the conduct of collaborative research across networks. METHODS: PERN has grown from five to eight member networks over the past decade. With an executive committee comprising representatives from all member networks, PERN plays a supportive and collaborative rather than governing role. The full impact of PERN's facilitation of international collaborative research, although somewhat difficult to quantify empirically, can be measured indirectly by the observed growth of the field, the nature of the increasingly challenging research questions now being addressed and the collective capacity to generate and implement new knowledge in treating acutely ill and injured children. RESULTS: Beginning as a pandemic response studying H1N1 influenza risk factors in children, PERN research has progressed to multiple observational studies and ongoing global randomised controlled trials (RCTs). As a recent example, PERN has developed sufficient network infrastructure to enable the rapid initiation of a prospective observational study in response to the current COVID-19 pandemic. CONCLUSIONS: Following its success with developing global research, the PERN goal now is to promote the implementation of scientific advances into everyday clinical practice by: (i) expanding the capacity for global RCTs; (ii) deepening the focus on implementation science; (iii) increasing attention to healthcare disparities; and (iv) expanding PERN's reach into resource-restricted regions. Through these actions, PERN aims to meet the needs of acutely ill and injured children throughout the world.

Advantages of visualisations to evaluate and communicate adverse event information in randomised controlled trials.

BACKGROUND: Randomised controlled trials (RCTs) provide valuable information and inform the development of harm profiles of new treatments. Harms are typically assessed through the collection of adverse events (AEs). Despite AEs being routine outcomes collected in trials, analysis and reporting of AEs in journal articles are continually shown to be suboptimal. One key challenge is the large volume of AEs, which can make evaluation and communication problematic. Prominent practice is to report frequency tables of AEs by arm. Visual displays offer an effective solution to assess and communicate complex information; however, they are rarely used and there is a lack of practical guidance on what and how to visually display complex AE data. METHODS: In this article, we demonstrate the use of two plots identified to be beneficial for wide use in RCTs, since both can display multiple AEs and are suitable to display point estimates for binary, count, or time-to-event AE data: the volcano and dot plots. We compare and contrast the use of data visualisations against traditional frequency table reporting, using published AE information in two placebo-controlled trials, of remdesivir for COVID-19 and GDNF for Parkinson disease. We introduce statistical programmes for implementation in Stata. RESULTS/CASE STUDY: Visualisations of AEs in the COVID-19 trial communicated a risk profile for remdesivir which differed from the main message in the published authors' conclusion. In the Parkinson's disease trial of GDNF, the visualisation provided immediate communication of harm signals, which had otherwise been contained within lengthy descriptive text and tables. Asymmetry in the volcano plot helped flag extreme events that were less obvious from review of the frequency table and dot plot. The dot plot allowed a more comprehensive representation by means of a more detailed summary. CONCLUSIONS: Visualisations can better support investigators to assimilate large volumes of data and enable improved informal between-arm comparisons compared to tables. We endorse increased uptake for use in trial publications. Care in construction of visual displays needs to be taken as there can be potential to overemphasise treatment effects in some circumstances.

Preserving equipoise and performing randomised trials for COVID-19 social distancing interventions.

In the coronavirus disease 2019 (COVID-19) pandemic, a large number of non-pharmaceutical measures that pertain to the wider group of social distancing interventions (e.g. public gathering bans, closures of schools, workplaces and all but essential business, mandatory stay-at-home policies, travel restrictions, border closures and others) have been deployed. Their urgent deployment was defended with modelling and observational data of spurious credibility. There is major debate on whether these measures are effective and there is also uncertainty about the magnitude of the harms that these measures might induce. Given that there is equipoise for how, when and if specific social distancing interventions for COVID-19 should be applied and removed/modified during reopening, we argue that informative randomised-controlled trials are needed. Only a few such randomised trials have already been conducted, but the ones done to-date demonstrate that a randomised trials agenda is feasible. We discuss here issues of study design choice, selection of comparators (intervention and controls), choice of outcomes and additional considerations for the conduct of such trials. We also discuss and refute common counter-arguments against the conduct of such trials.