Exploring the use and impact of the Australian living guidelines for the clinical care of people with COVID-19: where to from here?

OBJECTIVES: The 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 SETTING: A mixed-methods impact evaluation was conducted. Surveys collected both quantitative and qualitative data and were supplemented with qualitative interviews. Participants included Australian healthcare practitioners providing care to individuals with suspected or confirmed COVID-19 and people involved in policy-making. Data were collected on awareness, use, impact, strengths, and opportunities for improvement of the guidelines and flow charts. RESULTS: A total of 148 participants completed the survey and 21 people were interviewed between January and March 2022. Awareness of the work of the Taskforce was high and more than 75% of participants reported that the guidelines were used within their workplace. Participants described the Taskforce website and guidelines as trustworthy, valuable, and reliable sources of up-to-date evidence-based information. The evaluation highlighted the varied ways the guidelines were being used across a range of settings and the diverse impacts they have from those at a clinical level to impacts at a policy level. Barriers to and enablers of impact and uptake of the guideline were explored. CONCLUSION: This evaluation highlights the value of living guidelines during a pandemic when the evidence base is rapidly changing and expanding. It presents useful understanding of the ways clinicians and others use living evidence to inform their clinical practice and decision-making and the diverse impacts the guidelines are having around Australia.

Living evidence and adaptive policy: perfect partners?

BACKGROUND: While 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 the opportunities presented by living evidence for evidence-informed policy-making and highlight areas for further exploration. DISCUSSION: There are several elements of living approaches to evidence synthesis that might support increased and improved use of evidence to inform policy. Reviews are explicitly prioritised to be 'living' by partnerships between policy-makers and researchers based on relevance to decision-making, as well as uncertainty of existing evidence, and likelihood that new evidence will arise. The ongoing nature of the work means evidence synthesis teams can be dynamic and engage with policy-makers in a variety of ways over time; and synthesis topics, questions and methods can be adapted as policy interests or contextual factors shift. Policy-makers can sign-up to be notified when relevant new evidence is found, and can be confident that living syntheses are up-to-date and contain all research whenever they access them. The always up-to-date nature of living evidence syntheses means producers can rapidly demonstrate availability of relevant, reliable evidence when it is needed, addressing a frequently cited barrier to evidence-informed policymaking. CONCLUSIONS: While there are challenges to be overcome, living evidence provides opportunities to enable policy-makers to access up-to-date evidence whenever they need it and also enable researchers to respond to the issues of the day with up-to-date research; and update policy-makers on changes in the evidence base as they arise. It also provides an opportunity to build flexible partnerships between researchers and policy-makers to ensure that evidence syntheses reflect the changing needs of policy-makers.

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis.

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 Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world.

HIV treatment-as-prevention and its effect on incidence of HIV among cisgender gay, bisexual, and other men who have sex with men in Australia: a 10-year longitudinal cohort study.

BACKGROUND: Although 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. METHODS: TAIPAN 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 included HIV-negative patients. Population prevalence of viral suppression (plasma HIV viral load <200 RNA copies per µL) was calculated by combining direct measures of viral load among the HIV-positive cohort with estimates for undiagnosed GBM. The primary outcome of HIV incidence was measured directly via repeat testing in the HIV-negative cohort. Poisson regression analyses with generalised estimating equations assessed temporal associations between population prevalence of viral suppression and HIV incidence among the subsample of HIV-negative GBM with multiple instances of HIV testing. FINDINGS: At baseline, the final sample (n=101 772) included 90 304 HIV-negative and 11 468 HIV-positive GBM. 59 234 patients in the HIV-negative cohort had two or more instances of HIV testing and were included in the primary analysis. Over the study period, population prevalence of viral suppression increased from 69·27% (95% CI 66·41-71·96) to 88·31% (86·37-90·35), while HIV incidence decreased from 0·64 per 100 person-years (95% CI 0·55-0·76) to 0·22 per 100 person-years (0·17-0·28). Adjusting for sociodemographic characteristics and HIV pre-exposure prophylaxis (PrEP) use, treatment-as-prevention achieved significant population-level reductions in HIV incidence among GBM: a 1% increase in population prevalence of viral suppression corresponded with a 6% decrease in HIV incidence (incidence rate ratio [IRR] 0·94, 95% CI 0·93-0·96; p<0·0001). PrEP was introduced in 2016 with 17·60% uptake among GBM that year, which increased to 36·38% in 2019. The relationship between population prevalence of viral suppression and HIV incidence was observed before the availability of PrEP (IRR 0·98, 95% CI 0·96-0·99; p<0·0001) and was even stronger after the introduction of PrEP (0·80, 0·70-0·93; p=0·0030). INTERPRETATION: Our results suggest that further investment in HIV treatment, especially alongside PrEP, can improve public health by reducing HIV incidence among GBM. FUNDING: National Health and Medical Research Council of Australia.

Trace amine-associated receptor 1 (TAAR1) agonists for psychosis: protocol for a living systematic review and meta-analysis of human and non-human studies.

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. Two independent reviewers will conduct study selection, data extraction using predefined forms, and risk of bias assessment using suitable tools based on the study design. Ontologies will be developed to facilitate study identification and data extraction. Data from clinical and animal studies will be synthesized separately using random-effects meta-analysis if appropriate, or synthesis without meta-analysis. Study characteristics will be investigated as potential sources of heterogeneity. Confidence in the evidence for each outcome and source of evidence will be evaluated, considering the summary of the association, potential concerns regarding internal and external validity, and reporting biases. When multiple sources of evidence are available for an outcome, an overall conclusion will be drawn in a triangulation meeting involving a multidisciplinary team of experts. We plan trimonthly updates of the review, and any modifications in the protocol will be documented. The review will be co-produced by multiple stakeholders aiming to produce impactful and relevant results and bridge the gap between preclinical and clinical research on psychosis. PROTOCOL REGISTRATION: PROSPERO-ID: CRD42023451628.

The National COVID-19 Clinical Evidence Taskforce: pregnancy and perinatal guidelines.

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, breastfeeding, rooming-in, and using antenatal corticosteroids and magnesium sulfate as clinically indicated. There are 11 recommendations for COVID-19-specific treatments, including conditional recommendations for using remdesivir, tocilizumab and sotrovimab. Finally, there are recommendations not to use several disease-modifying treatments for the treatment of COVID-19, including hydroxychloroquine and ivermectin. The recommendations are continually updated to reflect new evidence, and the most up-to-date guidance is available online (https://covid19evidence.net.au). CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINES: The National COVID-19 Clinical Evidence Taskforce has been a critical component of the infrastructure to support Australian maternity care providers during the COVID-19 pandemic. The Taskforce has shown that a rapid living guidelines approach is feasible and acceptable.

Care for adults with COVID-19: living guidelines from the National COVID-19 Clinical Evidence Taskforce.

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: The Taskforce currently recommends eight drug treatments for people with COVID-19 who do not require supplemental oxygen (inhaled corticosteroids, casirivimab/imdevimab, molnupiravir, nirmatrelvir/ritonavir, regdanvimab, remdesivir, sotrovimab, tixagevimab/cilgavimab) and six for those who require supplemental oxygen (systemic corticosteroids, remdesivir, tocilizumab, sarilumab, baricitinib, casirivimab/imdevimab). Based on evidence of their achieving no or only limited benefit, ten drug treatments or treatment combinations are not recommended; an additional 42 drug treatments should only be used in the context of randomised trials. Additional recommendations include support for the use of continuous positive airway pressure, prone positioning, and endotracheal intubation in patients whose condition is deteriorating, and prophylactic anticoagulation for preventing venous thromboembolism. The latest updates and full recommendations are available at www.covid19evidence.net.au.

Changes in dispensing of medicines proposed for re-purposing in the first year of the COVID-19 pandemic in Australia.

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 stockpiling, we observed no change in the initiation of calcitriol or colchicine during COVID-19. Dispensing of corticosteroids and azithromycin was lower than expected from April through November 2020. CONCLUSIONS: While most increases in dispensing observed early on during COVID-19 were temporary and appear to be related to stockpiling among existing users, we observed increases in the initiation of hydroxychloroquine and ivermectin and a shift in prescribing patterns which may be related to the media hype around these medicines. A quick response by regulators can help limit inappropriate repurposing to lessen the impact on medicine supply and patient harm.

Accuracy and Efficiency of Machine Learning-Assisted Risk-of-Bias Assessments in "Real-World" Systematic Reviews : A Noninferiority Randomized Controlled Trial.

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. INTERVENTION: In the intervention group, reviewers received an RoB form prepopulated by RobotReviewer; in the comparison group, reviewers received a blank form. Studies were assigned in a 1:1 ratio via simple randomization to receive RobotReviewer assistance for either Reviewer 1 or Reviewer 2. Participants were blinded to study allocation before starting work on each RoB form. MEASUREMENTS: Co-primary outcomes were the accuracy of individual reviewer RoB assessments and the person-time required to complete individual assessments. Domain-level RoB accuracy was a secondary outcome. RESULTS: Of the 15 recruited review teams, 7 completed the trial (145 included studies). Integration of RobotReviewer resulted in noninferior overall RoB assessment accuracy (risk difference, -0.014 [95% CI, -0.093 to 0.065]; intervention group: 88.8% accurate assessments; control group: 90.2% accurate assessments). Data were inconclusive for the person-time outcome (RobotReviewer saved 1.40 minutes [CI, -5.20 to 2.41 minutes]). LIMITATION: Variability in user behavior and a limited number of assessable reviews led to an imprecise estimate of the time outcome. CONCLUSION: In health-related systematic reviews, RoB assessments conducted with RobotReviewer assistance are noninferior in accuracy to those conducted without RobotReviewer assistance. PRIMARY FUNDING SOURCE: University College London and Monash University.

Editorial.

During its 128 years of operation, Psychological Review has exerted a powerful and consistent influence on the field under its long-term sponsor, the American Psychological Association (APA). Notwithstanding changes in ownership, it has always been what it is now-the flagship of the Association and the field. Since its inception, the journal has focused on theoretical analyses (e.g., systematic evaluations of alternative theories) and/or developments (e.g., the generation of novel theories) in the psychological sciences. Thus, the objectives of any incoming editor and editorial board remain steadfast: (a) to maintain and enhance the standing of Psychological Review in the field and (b) to correspondingly align its scope, content, and operations with any changes in the Association, the field of psychology in particular, and science and society in general. The journal's new senior editorial team is excited to navigate Psychological Review through the ever-changing landscape of psychology at this time of multiple challenges, referred to by the United Nations Secretary General António Guterres as "the greatest cascade of crises in our lifetime." Although we are initiating a number of changes, we will do our best to maintain Psychological Review's excellence. This will involve our capacity to reflect on and disseminate new theoretical developments, enriched and inspired by current trends in science in general and in psychological science in particular, while maintaining an overarching commitment to advancing the field through the incorporation of diverse perspectives. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Perspectives of patients, family members, health professionals and the public on the impact of COVID-19 on mental health.

BACKGROUND: The coronavirus (COVID-19) pandemic has seen a global surge in anxiety, depression, post-traumatic stress disorder (PTSD), and stress. AIMS: This 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. METHODS: A 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. RESULTS: We 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 transmission (fear of spreading COVID-19 in public; overwhelming guilt of infecting a loved one); and suffering in isolation (severe solitude of quarantine, sick and alone, separation exacerbating grief). CONCLUSION: We found that the unpredictability of COVID-19, the fear of long-term health consequences, burden of guilt, and suffering in isolation profoundly impacted mental health. Clinical and public health interventions are needed to manage the psychological consequences arising from this pandemic.

The Australian living guidelines for the clinical care of people with COVID-19: What worked, what didn't and why, a mixed methods process evaluation.

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 work of the Taskforce were identified. CONCLUSIONS: In just over 5 months of activity, the National COVID-19 Clinical Evidence Taskforce published 20 weekly updates to the evidence-based national treatment guidelines for COVID-19. This process evaluation identified several factors that enabled this achievement (e.g. an extant skill base in evidence review and convening), along with challenges that needed to be overcome (e.g. managing workloads, structure and governance) and methods questions (pace of updating, and thresholds for inclusion of evidence) which may be useful considerations for other living guidelines projects. An impact evaluation is also being conducted separately to examine awareness, acceptance and use of the guidelines.

Awareness, value and use of the Australian living guidelines for the clinical care of people with COVID-19: an impact evaluation.

BACKGROUND AND OBJECTIVE: The 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. METHODS: A 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, and strengths and opportunities for improvement. RESULTS: A total of 287 people completed the surveys and 10 interviews were conducted during November 2020. Awareness of the work of the Taskforce was high and the vast majority of respondents reported that the guidelines were very or extremely relevant, easy to use, trustworthy and valuable. More than 50% of respondents had used the guidelines to support their own clinical decision-making; and 30% were aware of other examples of the guidelines being used. Qualitative data revealed that amongst an overwhelming morass of evidence and opinions during the COVID-19 pandemic, the guidelines have been a reliable, united source of evidence-based advice; participants felt the guidelines built confidence and provided reassurance in clinical decision-making. Opportunities to improve awareness and accessibility to the guidelines were also explored. CONCLUSIONS: As of June 2021, the guidelines have been published and updated more than 40 times, include more than 140 recommendations and are being used to inform clinical decisions. The findings of this impact evaluation will be used to improve processes and outputs of the Taskforce and guidelines project, and to inform future living guideline projects.

Care of older people and people requiring palliative care with COVID-19: guidance from the Australian National COVID-19 Clinical Evidence Taskforce.

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 flow charts focus on goals of care, communication, medication management, escalation of care, active disease-directed care, and managing symptoms such as delirium, anxiety, agitation, breathlessness or cough. The Taskforce also developed living guideline recommendations for the care of adults with COVID-19, including a commentary to discuss special considerations when caring for older people and those requiring palliative care. CHANGES IN MANAGEMENT AS RESULT OF THE GUIDELINE: The practice points in the flow charts emphasise quality clinical care, with a focus on addressing the most important challenges when caring for older individuals and people with COVID-19 requiring palliative care. The adult recommendations contain additional considerations for the care of older people and those requiring palliative care.

Living Systematic Reviews.

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 to detect a genuine effect) and take account of heterogeneity.

A New Method for Estimating the Incidence of Infectious Diseases.

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 applied the methods to assess human immunodeficiency virus (HIV) incidence in HIV-negative patients from the Treatment With Antiretrovirals and Their Impact on Positive and Negative Men (TAIPAN) Study, an Australian study of HIV incidence in men who have sex with men, between 2012 and 2018. The Poisson binomial method had reduced bias and variance at low levels of incidence and for increased estimation frequency, with increased consistency of estimation. Application of methods to real-world assessment of HIV incidence found decreased variance in Poisson binomial model estimates, with observed incidence declining to levels where simulation results had indicated bias in midpoint and random-point methods.

The views of health guideline developers on the use of automation in health evidence synthesis.

BACKGROUND: The increasingly rapid rate of evidence publication has made it difficult for evidence synthesis-systematic reviews and health guidelines-to be continually kept up to date. One proposed solution for this is the use of automation in health evidence synthesis. Guideline developers are key gatekeepers in the acceptance and use of evidence, and therefore, their opinions on the potential use of automation are crucial. METHODS: The objective of this study was to analyze the attitudes of guideline developers towards the use of automation in health evidence synthesis. The Diffusion of Innovations framework was chosen as an initial analytical framework because it encapsulates some of the core issues which are thought to affect the adoption of new innovations in practice. This well-established theory posits five dimensions which affect the adoption of novel technologies: Relative Advantage, Compatibility, Complexity, Trialability, and Observability. Eighteen interviews were conducted with individuals who were currently working, or had previously worked, in guideline development. After transcription, a multiphase mixed deductive and grounded approach was used to analyze the data. First, transcripts were coded with a deductive approach using Rogers' Diffusion of Innovation as the top-level themes. Second, sub-themes within the framework were identified using a grounded approach. RESULTS: Participants were consistently most concerned with the extent to which an innovation is in line with current values and practices (i.e., Compatibility in the Diffusion of Innovations framework). Participants were also concerned with Relative Advantage and Observability, which were discussed in approximately equal amounts. For the latter, participants expressed a desire for transparency in the methodology of automation software. Participants were noticeably less interested in Complexity and Trialability, which were discussed infrequently. These results were reasonably consistent across all participants. CONCLUSIONS: If machine learning and other automation technologies are to be used more widely and to their full potential in systematic reviews and guideline development, it is crucial to ensure new technologies are in line with current values and practice. It will also be important to maximize the transparency of the methods of these technologies to address the concerns of guideline developers.

An evaluation of Cochrane Crowd found that crowdsourcing produced accurate results in identifying randomized trials.

BACKGROUND AND OBJECTIVES: Filtering the deluge of new research to facilitate evidence synthesis has proven to be unmanageable using current paradigms of search and retrieval. Crowdsourcing, a way of harnessing the collective effort of a "crowd" of people, has the potential to support evidence synthesis by addressing this information overload created by the exponential growth in primary research outputs. Cochrane Crowd, Cochrane's citizen science platform, offers a range of tasks aimed at identifying studies related to health care. Accompanying each task are brief, interactive training modules, and agreement algorithms that help ensure accurate collective decision-making.The aims of the study were to evaluate the performance of Cochrane Crowd in terms of its accuracy, capacity, and autonomy and to examine contributor engagement across three tasks aimed at identifying randomized trials. STUDY DESIGN AND SETTING: Crowd accuracy was evaluated by measuring the sensitivity and specificity of crowd screening decisions on a sample of titles and abstracts, compared with "quasi gold-standard" decisions about the same records using the conventional methods of dual screening. Crowd capacity, in the form of output volume, was evaluated by measuring the number of records processed by the crowd, compared with baseline. Crowd autonomy, the capability of the crowd to produce accurate collectively derived decisions without the need for expert resolution, was measured by the proportion of records that needed resolving by an expert. RESULTS: The Cochrane Crowd community currently has 18,897 contributors from 163 countries. Collectively, the Crowd has processed 1,021,227 records, helping to identify 178,437 reports of randomized controlled trials (RCTs) for Cochrane's Central Register of Controlled Trials. The sensitivity for each task was 99.1% for the RCT identification task (RCT ID), 99.7% for the RCT identification task of trials from ClinicalTrials.gov (CT ID), and 97.7% for the identification of RCTs from the International Clinical Trials Registry Platform (ICTRP ID). The specificity for each task was 99% for RCT ID, 98.6% for CT ID, and 99.1% for CT ICTRP ID. The capacity of the combined Crowd and machine learning workflow has increased fivefold in 6 years, compared with baseline. The proportion of records requiring expert resolution across the tasks ranged from 16.6% to 19.7%. CONCLUSION: Cochrane Crowd is sufficiently accurate and scalable to keep pace with the current rate of publication (and registration) of new primary studies. It has also proved to be a popular, efficient, and accurate way for a large number of people to play an important voluntary role in health evidence production. Cochrane Crowd is now an established part of Cochrane's effort to manage the deluge of primary research being produced.