Julian Elliott

ObjectivesThe Australian National COVID-19 Clinical Evidence Taskforce has been developing, maintaining, and disseminating living guidelines and decision support tools (clinical flowcharts) for the care of people with suspected or confirmed COVID-19 since 2020. Living guidelines, a form of living evidence, are a relatively new approach; hence, more work is required to determine how to optimize their use to inform practice, policy, and decision-making and to explore implementation, uptake, and impact implications. An update of an earlier impact evaluation was conducted to understand sustained awareness and use of the guidelines; the factors that facilitate the widespread adoption of the guidelines and to explore the perceived strengths and opportunities for improvement of the guidelines.Study Design and SettingA mixed-methods impact evaluation was conducted. Surveys collected both quantitative and …

A scoping review, the aim of which is to map the existing methodological evidence on how to conduct a pairwise or network meta-analysis in the context of updated or living systematic reviews

BACKGROUND Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies. METHODS We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses. RESULTS Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to …

BackgroundWhile there has been widespread global acceptance of the importance of evidence-informed policy, many opportunities to inform health policy with research are missed, often because of a mismatch between when and where reliable evidence is needed, and when and where it is available. ‘Living evidence’ is an approach where systematic evidence syntheses (e.g. living reviews, living guidelines, living policy briefs, etc.) are continually updated to incorporate new relevant evidence as it becomes available. Living evidence approaches have the potential to overcome a major barrier to evidence-informed policy, making up-to-date systematic summaries of policy-relevant research available at any time that policy-makers need them. These approaches are likely to be particularly beneficial given increasing calls for policy that is responsive, and rapidly adaptive to changes in the policy context.We describe …

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global …

BackgroundAlthough HIV treatment-as-prevention reduces individual-level HIV transmission, population-level effects are unclear. We aimed to investigate whether treatment-as-prevention could achieve population-level reductions in HIV incidence among gay, bisexual, and other men who have sex with men (GBM) in Australia's most populous states, New South Wales and Victoria.MethodsTAIPAN was a longitudinal cohort study using routine health record data extracted from 69 health services that provide HIV diagnosis and care to GBM in New South Wales and Victoria, Australia. Data from Jan 1, 2010, to Dec 31, 2019, were linked within and between services and over time. TAIPAN collected data from all cisgender GBM who attended participating services, resided in New South Wales or Victoria, and were 16 years or older. Two cohorts were established: one included HIV-positive patients, and the other …

Background: There is an urgent need to develop more effective and safer antipsychotics beyond dopamine 2 receptor antagonists. An emerging and promising approach is TAAR1 agonism. Therefore, we will conduct a living systematic review and meta-analysis to synthesize and triangulate the evidence from preclinical animal experiments and clinical studies on the efficacy, safety, and underlying mechanism of action of TAAR1 agonism for psychosis.Methods: Independent searches will be conducted in multiple electronic databases to identify clinical and animal experimental studies comparing TAAR1 agonists with licensed antipsychotics or other control conditions in individuals with psychosis or animal models for psychosis, respectively. The primary outcomes will be overall psychotic symptoms and their behavioural proxies in animals. Secondary outcomes will include side effects and neurobiological measures …

Systematic reviews are difficult to keep up to date, but failure to do so leads to poor review currency and accuracy. “Living systematic review” (LSR) is an approach that aims to continually update a review, incorporating relevant new evidence as it becomes available. LSRs may be particularly important in fields where research evidence is emerging rapidly, current evidence is uncertain, and new research may change policy or practice decisions. This chapter describes the concept and processes of living systematic reviews. It describes the general principles of LSRs, when they might be of particular value, and how their procedures differ from conventional systematic reviews. The chapter focuses particularly on two methods of sequential meta-analysis that may be particularly useful for LSRs: Trial Sequential Analysis and Sequential Meta-Analysis, which both control for Type I error, Type II error (failing …

Introduction Pregnant women are at higher risk of severe illness from coronavirus disease 2019 (COVID‐19) than non‐pregnant women of a similar age. Early in the COVID‐19 pandemic, it was clear that evidenced‐based guidance was needed, and that it would need to be updated rapidly. The National COVID‐19 Clinical Evidence Taskforce provided a resource to guide care for people with COVID‐19, including during pregnancy. Care for pregnant and breastfeeding women and their babies was included as a priority when the Taskforce was set up, with a Pregnancy and Perinatal Care Panel convened to guide clinical practice. Main recommendations As of May 2022, the Taskforce has made seven specific recommendations on care for pregnant women and those who have recently given birth. This includes supporting usual practices for the mode of birth, umbilical cord clamping, skin‐to‐skin contact …

Extensive research suggests that ideal worker and mothering expectations have long constrained academic mothers’ personal and professional choices. This article explores how academic mothers experienced their dual roles amid the unprecedented shift in the work-life landscape due to COVID-19. Content analysis of questionnaire data (n = 141) suggests that academic mothers experienced significant bidirectional work-life conflict well into the fall of 2020. Increased home demands, such as caring for young children and remote schooling, interfered with their perceived capacity to meet ideal academic norms, including a singular focus on work, productivity standards, and their ability to signal job competency and commitment. Likewise, work demands reduced their perceived ability to meet ideal mothering norms, such as providing a nurturing presence and focusing on their children’s achievement …

The methods of systematic review are well developed but resource intensive, which limits the feasibility, timeliness, and currency of high‐quality evidence synthesis. Several new technologies and processes are emerging that address these challenges by improving the efficiency of systematic review production. Specialized software platforms continue to develop functionality that improves workflow and review team collaboration. Text mining and machine learning algorithms are being developed to semi‐automate the most time‐consuming tasks in systematic review, for example by reducing the number of citations to be screened. Many review tasks are also amenable to crowdsourced contributions from citizen scientists. Underpinning these innovations is the development of metadata systems that can enhance the discoverability and reuse of research and …

Introduction The Australian National COVID‐19 Clinical Evidence Taskforce was established in March 2020 to maintain up‐to‐date recommendations for the treatment of people with coronavirus disease 2019 (COVID‐19). The original guideline (April 2020) has been continuously updated and expanded from nine to 176 recommendations, facilitated by the rapid identification, appraisal, and analysis of clinical trial findings and subsequent review by expert panels. Main recommendations In this article, we describe the recommendations for treating non‐pregnant adults with COVID‐19, as current on 1 August 2022 (version 61.0). The Taskforce has made specific recommendations for adults with severe/critical or mild disease, including definitions of disease severity, recommendations for therapy, COVID‐19 prophylaxis, respiratory support, and supportive care. Changes in management as a result of the guideline …

Introduction Older people living with frailty and/or cognitive impairment who have coronavirus disease 2019 (COVID‐19) experience higher rates of critical illness. There are also people who become critically ill with COVID‐19 for whom a decision is made to take a palliative approach to their care. The need for clinical guidance in these two populations resulted in the formation of the Care of Older People and Palliative Care Panel of the National COVID‐19 Clinical Evidence Taskforce in June 2020. This specialist panel consists of nursing, medical, pharmacy and allied health experts in geriatrics and palliative care from across Australia. Main recommendations The panel was tasked with developing two clinical flow charts for the management of people with COVID‐19 who are i) older and living with frailty and/or cognitive impairment, and ii) receiving palliative care for COVID‐19 or other underlying illnesses. The …

BackgroundThe coronavirus (COVID-19) pandemic has seen a global surge in anxiety, depression, post-traumatic stress disorder (PTSD), and stress.AimsThis study aimed to describe the perspectives of patients with COVID-19, their family, health professionals, and the general public on the impact of COVID-19 on mental health.MethodsA secondary thematic analysis was conducted using data from the COVID-19 COS project. We extracted data on the perceived causes and impact of COVID-19 on mental health from an international survey and seven online consensus workshops.ResultsWe identified four themes (with subthemes in parenthesis): anxiety amidst uncertainty (always on high alert, ebb and flow of recovery); anguish of a threatened future (intense frustration of a changed normality, facing loss of livelihood, trauma of ventilation, a troubling prognosis, confronting death); bearing responsibility for …

Background Automation is a proposed solution for the increasing difficulty of maintaining up-to-date, high-quality health evidence. Evidence assessing the effectiveness of semiautomated data synthesis, such as risk-of-bias (RoB) assessments, is lacking. Objective To determine whether RobotReviewer-assisted RoB assessments are noninferior in accuracy and efficiency to assessments conducted with human effort only. Design Two-group, parallel, noninferiority, randomized trial. (Monash Research Office Project 11256) Setting Health-focused systematic reviews using Covidence. Participants Systematic reviewers, who had not previously used RobotReviewer, completing Cochrane RoB assessments between February 2018 and May 2020 …

Background and ObjectiveThe Australian National COVID-19 Clinical Evidence Taskforce is developing living, evidence-based, national guidelines for treatment of people with COVID-19. These living guidelines are updated each week. We undertook an impact evaluation to understand the extent to which health professionals providing treatment to people with COVID 19 were aware of, valued and used the guidelines, and the factors that enabled or hampered this.MethodsA mixed methods approach was used for the evaluation. Surveys were conducted to collect both quantitative and qualitative data and were supplemented with qualitative interviews. Australian healthcare practitioners potentially providing care to individuals with suspected or confirmed COVID-19 were invited to participate. Data were collected on guideline awareness, relevance, ease of use, trustworthiness, value, importance of updating, use …

Background Since COVID-19 was first recognised, there has been ever-changing evidence and misinformation around effective use of medicines. Understanding how pandemics impact on medicine use can help policymakers act quickly to prevent harm. We quantified changes in dispensing of common medicines proposed for “re-purposing” due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia. Methods We performed an interrupted time series analysis and cross-sectional study using nationwide dispensing claims data (January 2017-November 2020). We focused on six subsidized medicines proposed for re-purposing: hydroxychloroquine, azithromycin, ivermectin, colchicine, corticosteroids, and calcitriol (Vitamin D analog). We quantified changes in monthly dispensing and initiation trends during COVID-19 (March-November 2020) using autoregressive integrated moving average models and compared characteristics of initiators in 2020 and 2019. Results In March 2020, we observed a 99% (95%CI: 96%-103%) increase in hydroxychloroquine dispensing (approximately 22% attributable to new users), and a 199% increase (95%CI: 184%-213%) in initiation, with an increase in prescribing by general practitioners (42% in 2020 vs 25% in 2019) rather than specialists. These increases subsided following regulatory restrictions on prescribing. There was a small but sustained increase in ivermectin dispensing over multiple months, with an 80% (95%CI 42%-118%) increase in initiation in May 2020 following its first identification as potentially disease-modifying in April. Other than increases in March related to …

Introduction The Australian National COVID-19 Clinical Evidence Taskforce is producing living, evidence-based, national guidelines for treatment of people with COVID-19 which are updated each week. To continually improve the process and outputs of the Taskforce, and inform future living guideline development, we undertook a concurrent process evaluation examining Taskforce activities and experience of team members and stakeholders during the first 5 months of the project. Methods The mixed-methods process evaluation consisted of activity and progress audits, an online survey of all Taskforce participants; and semi-structured interviews with key contributors. Data were collected through five, prospective 4-weekly timepoints (beginning first week of May 2020) and three, fortnightly retrospective timepoints (March 23, April 6 and 20). We collected and analysed quantitative and qualitative data. Results An updated version of the guidelines was successfully published every week during the process evaluation. The Taskforce formed in March 2020, with a nominal start date of March 23. The first version of the guideline was published two weeks later and included 10 recommendations. By August 24, in the final round of the process evaluation, the team of 11 staff, working with seven guideline panels and over 200 health decision-makers, had developed 66 recommendations addressing 58 topics. The Taskforce website had received over 200,000 page views. Satisfaction with the work of the Taskforce remained very high (>90% extremely or somewhat satisfied) throughout. Several key strengths, challenges and methods questions for the …

OBJECTIVES:Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019.DESIGN:Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery.SETTING:International.PATIENTS:About 130 participants (patients, public, and health professionals) from 17 countries attended the three workshops.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:

Ambitious World Health Organization targets for disease elimination require monitoring of epidemics using routine health data in settings of decreasing and low incidence. We evaluated 2 methods commonly applied to routine testing results to estimate incidence rates that assume a uniform probability of infection between consecutive negative and positive tests based on 1) the midpoint of this interval and 2) a randomly selected point in this interval. We compared these with an approximation of the Poisson binomial distribution, which assigns partial incidence to time periods based on the uniform probability of occurrence in these intervals. We assessed bias, variance, and convergence of estimates using simulations of Weibull-distributed failure times with systematically varied baseline incidence and varying trend. We considered results for quarterly, half-yearly, and yearly incidence estimation frequencies. We …