Anti-Vascular Endothelial Growth Factor Drugs Compared With Panretinal Photocoagulation for the Treatment of Proliferative Diabetic Retinopathy: A Cost-Effectiveness Analysis.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of anti-vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. METHODS: A discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. RESULTS: Anti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of £3688, with a net health benefit of -0.214 at a £20 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. CONCLUSIONS: Anti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties.

A structured approach to information retrieval improved identification of funding and researchers' conflicts of interest in trials included in Cochrane reviews.

OBJECTIVES: To compare the contemporary Cochrane review approach for retrieving information on trial funding and researchers' conflicts of interest with a structured approach for information retrieval. STUDY DESIGN AND SETTING: Methodological study of 100 Cochrane reviews from August to December 2020 and one randomly selected trial from each review. Reporting of trial funding and researchers' conflicts of interest in reviews was compared with information identified using a structured retrieval process, and time to retrieve information was noted. We also formulated a guide to systematic reviewers for efficient information retrieval. RESULTS: Sixty-eight of 100 Cochrane reviews reported trial funding and 24 reported trial researchers' conflicts of interest. A simple structured approach, searching only trial publications (including conflicts of interest disclosure forms), identified funding for 16 additional trials and conflicts of interest information for 39 additional trials. A comprehensive structured approach, searching multiple information sources, identified funding for two additional trials and conflicts of interest for 14 additional trials. The median time to retrieve information was 10 minutes per trial (interquartile range: 7-15) for the simple approach and 20 minutes (11-43) for the comprehensive approach. CONCLUSION: A structured information retrieval approach improves identification of funding and researchers' conflicts of interest in trials included in Cochrane reviews.

Retrieval barriers in individual participant data reviews with network meta-analysis.

OBJECTIVES: Individual participant data (IPD) from randomised controlled trials (RCTs) can be used in network meta-analysis (NMA) to underpin patient care and are the best analyses to support the development of guidelines about the use of healthcare interventions for a specific condition. However, barriers to IPD retrieval pose a major threat. The aim of this study was to present barriers we encountered during retrieval of IPD from RCTs in two published systematic reviews with IPD-NMA. METHODS: We evaluated retrieval of IPD from RCTs for IPD-NMA in Alzheimer's dementia and type 1 diabetes. We requested IPD from authors, industry sponsors and data repositories, and recorded IPD retrieval, reasons for IPD unavailability, and retrieval challenges. RESULTS: In total, we identified 108 RCTs: 78 industry sponsored, 11 publicly sponsored and 19 with no funding information. After failing to obtain IPD from any trial authors, we requested it from industry sponsors. Seven of the 17 industry sponsors shared IPD for 12 950 participants (59%) through proprietary-specific data sharing platforms from 26 RCTs (33%). We found that lack of RCT identifiers (eg, National Clinical Trial number) and unclear data ownership were major challenges in IPD retrieval. Incomplete information in retrieved datasets was another important problem that led to exclusion of RCTs from the NMA. There were also practical challenges in obtaining IPD from or analysing it within platforms, and additional costs were incurred in accessing IPD this way. CONCLUSIONS: We found no clear evidence of retrieval bias (where IPD availability was linked to trial findings) in either IPD-NMA, but because retrieval bias could impact NMA findings, subsequent decision-making and guideline development, this should be considered when assessing risk of bias in IPD syntheses.

Using individual participant data to improve network meta-analysis projects.

A network meta-analysis combines the evidence from existing randomised trials about the comparative efficacy of multiple treatments. It allows direct and indirect evidence about each comparison to be included in the same analysis, and provides a coherent framework to compare and rank treatments. A traditional network meta-analysis uses aggregate data (eg, treatment effect estimates and standard errors) obtained from publications or trial investigators. An alternative approach is to obtain, check, harmonise and meta-analyse the individual participant data (IPD) from each trial. In this article, we describe potential advantages of IPD for network meta-analysis projects, emphasising five key benefits: (1) improving the quality and scope of information available for inclusion in the meta-analysis, (2) examining and plotting distributions of covariates across trials (eg, for potential effect modifiers), (3) standardising and improving the analysis of each trial, (4) adjusting for prognostic factors to allow a network meta-analysis of conditional treatment effects and (5) including treatment-covariate interactions (effect modifiers) to allow relative treatment effects to vary by participant-level covariate values (eg, age, baseline depression score). A running theme of all these benefits is that they help examine and reduce heterogeneity (differences in the true treatment effect between trials) and inconsistency (differences in the true treatment effect between direct and indirect evidence) in the network. As a consequence, an IPD network meta-analysis has the potential for more precise, reliable and informative results for clinical practice and even allows treatment comparisons to be made for individual patients and targeted populations conditional on their particular characteristics.

Extent and nature of duplication in PROSPERO using COVID-19-related registrations: a retrospective investigation and survey.

OBJECTIVES: During COVID-19, the International Prospective Register of Systematic Reviews (PROSPERO) experienced a surge in registrations for COVID-19-related systematic reviews, and duplication of research questions became apparent. Duplication can waste funding, time and research effort and make policy making more difficult.This project explored the extent of and reasons for duplication of COVID-19-related systematic review registrations in PROSPERO during the pandemic. DESIGN: Retrospective analysis of COVID-19-related registrations in PROSPERO, and a qualitative survey. SETTING: PROSPERO was searched for registrations related to four COVID-19 research areas: epidemiology, rehabilitation, transmission and treatments. METHODS: Records identified were compared using Population, Intervention/Exposure, Comparator, Outcome, Study Design (PICOS) elements of PROSPERO registration forms. Registrations with similar or identical PICOS were evaluated further as 'duplicates'.Authors of 'duplicate' registrations were invited to complete a survey asking whether they searched PROSPERO prior to registration, identified similar reviews and, if so, why they continued with their review. RESULTS: 1054 COVID-19 reviews were registered between March 2020 and January 2021, of which 138 were submitted when at least one similar protocol was already registered in PROSPERO. Duplication was greatest in reviews of COVID-19 treatments; for example, there were 14 similar reviews evaluating the efficacy of hydroxychloroquine.From 138 authors invited to take part in the survey, we received 41 responses. Most respondents said that they identified similar reviews when they searched PROSPERO prior to registration. Main reasons given for 'duplication' were differences in PICOS or planned analyses (n=13), poor quality of previous registrations (n=2) and the need to update evidence (n=3). CONCLUSIONS: This research highlights that registration of similar and duplicate systematic reviews related to COVID-19 in PROSPERO occurred frequently. Awareness of research waste is required, and initial checking for similar reviews should be embedded within good review practice.

Comparative efficacy and complications of long-acting and intermediate-acting insulin regimens for adults with type 1 diabetes: an individual patient data network meta-analysis.

OBJECTIVE: To examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus (T1DM). DESIGN: Systematic review and individual patient data (IPD) network meta-analysis (NMA). DATA SOURCES: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through June 2015. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) on adults with T1DM assessing glycosylated haemoglobin (A1c) and severe hypoglycaemia in long-acting and intermediate-acting insulin regimens. DATA EXTRACTION AND SYNTHESIS: We requested IPD from authors and funders. When IPD were not available, we used aggregate data. We conducted a random-effects model, and specifically a one-stage IPD-NMA for those studies providing IPD and a two-stage IPD-NMA to incorporate those studies not providing IPD. RESULTS: We included 28 RCTs plus one companion report, after screening 6680 titles/abstracts and 205 full-text articles. Of the 28 RCTs, 27 studies provided data for the NMA with 7394 participants, of which 12 RCTs had IPD on 4943 participants. The IPD-NMA for A1c suggested that glargine once daily (mean difference [MD]=-0.31, 95% confidence interval [CI]: -0.48 to -0.14) and detemir once daily (MD=-0.25, 95% CI: -0.41 to -0.09) were superior to neutral protamine Hagedorn (NPH) once daily. NPH once/two times per day improved A1c compared with NPH once daily (MD=-0.30, 95% CI: -0.50 to -0.11). Results regarding complications in severe hypoglycaemia should be considered with great caution due to inconsistency in the evidence network. Accounting for missing data, there was no evidence of inconsistency and long-acting insulin regimens ranked higher regarding reducing severe hypoglycaemia compared with intermediate-acting insulin regimens (two-stage NMA: glargine two times per day SUCRA (Surface Under the Cumulative Ranking curve)=89%, detemir once daily SUCRA=77%; one-stage NMA: detemir once daily/two times per day SUCRA=85%). Using multiple imputations and IPD only, complications in severe hypoglycaemia increased with diabetes-related comorbidities (regression coefficient: 1.03, 95% CI: 1.02 to 1.03). CONCLUSIONS: Long-acting insulin regimens reduced A1c compared with intermediate-acting insulin regimens and were associated with lower severe hypoglycaemia. Of the observed differences, only glargine once daily achieved a clinically significant reduction of 0.30%. Results should be interpreted with caution due to very low quality of evidence. PROSPERO REGISTRATION NUMBER: CRD42015023511.

Estimating interactions in individual participant data meta-analysis: a comparison of methods in practice.

Medical interventions may be more effective in some types of individuals than others and identifying characteristics that modify the effectiveness of an intervention is a cornerstone of precision or stratified medicine. The opportunity for detailed examination of treatment-covariate interactions can be an important driver for undertaking an individual participant data (IPD) meta-analysis, rather than a meta-analysis using aggregate data. A number of recent modelling approaches are available. We apply these methods to the Perinatal Antiplatelet Review of International Studies (PARIS) Collaboration IPD dataset and compare estimates between them. We discuss the practical implications of applying these methods, which may be of interest to aid meta-analysists in the use of these, often complex models.Models compared included the two-stage meta-analysis of interaction terms and one-stage models which fit multiple random effects and separate within and between trial information. Models were fitted for nine covariates and five binary outcomes and results compared.Interaction terms produced by the methods were generally consistent. We show that where data are sparse and there is low heterogeneity in the covariate distributions across trials, the meta-analysis of interactions may produce unstable estimates and have issues with convergence. In this IPD dataset, varying assumptions by using multiple random effects in one-stage models or using only within trial information made little difference to the estimates of treatment-covariate interaction. Method choice will depend on datasets characteristics and individual preference.

Intensive behavioural interventions based on applied behaviour analysis (ABA) for young children with autism: A cost-effectiveness analysis.

BACKGROUND: The economic and social costs of autism are significant. This study evaluates the cost-effectiveness of early intensive Applied Behaviour Analysis (ABA)-based interventions for autistic pre-school children in the UK. METHODS: A de novo economic analysis was developed in Microsoft Excel comparing early intensive ABA-based interventions compared with treatment as usual (TAU). The analysis used 15.5-year time horizon, with costs and benefits discounted a 3.5%. The model structure was based on cohort structure to capture changes in adaptive behaviour and cognitive ability over time. The analysis was informed by an individual patient data (IPD) meta-analysis of available evidence. RESULTS: Adopting a public sector perspective, early intensive ABA-based therapies were associated with greater incremental costs and greater benefits. When pessimistic assumptions were made regarding the long-term effects of treatment incremental costs were £46,103 and incremental quality-adjusted life years (QALYs) were 0.24, resulting in an incremental cost-effectiveness ratio (ICER) of £189,122 per quality-adjusted life year (QALY). When optimistic assumptions were made about long-term effects, incremental costs were £39,233 with incremental benefits of 0.84 QALYs. The resulting ICER was £46,768 per QALY. Scenario analyses emphasised the importance of assumptions made regarding adult outcomes and type of school attended, both of which significantly affect the results of the analysis. CONCLUSIONS: The results of this economic analysis suggest that early intensive ABA-based interventions are unlikely to represent value for money, based on a £20,000 to £30,000 per QALY threshold typically adopted to inform UK healthcare funding decisions. However, important gaps in the available evidence, limit the strength of the conclusions that can be drawn from the presented analysis. Further research, focusing on the trajectory of autistic children following intervention is likely to be highly beneficial to resolving some of these uncertainties.

Comparative safety and efficacy of cognitive enhancers for Alzheimer's dementia: a systematic review with individual patient data network meta-analysis.

OBJECTIVE: To examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer's dementia (AD). DESIGN: Systematic review and individual patient data (IPD) network meta-analysis (NMA) based on our previously published systematic review and aggregate data NMA. DATA SOURCES: MEDLINE, Embase, Cochrane Methodology Register, CINAHL, AgeLine and Cochrane Central Register of Controlled Trials up to March 2016. PARTICIPANTS: 80 randomised controlled trials (RCTs) including 21 138 adults with AD, and 12 RCTs with IPD including 6906 patients. INTERVENTIONS: Cognitive enhancers (donepezil, rivastigmine, galantamine and memantine) alone or in any combination against other cognitive enhancers or placebo. DATA EXTRACTION AND SYNTHESIS: We requested IPD from authors, sponsors and data sharing platforms. When IPD were not available, we used aggregate data. We appraised study quality with the Cochrane risk-of-bias. We conducted a two-stage random-effects IPD-NMA, and assessed their findings using CINeMA (Confidence in Network Meta-Analysis). PRIMARY AND SECONDARY OUTCOMES: We included trials assessing cognition with the Mini-Mental State Examination (MMSE), and adverse events. RESULTS: Our IPD-NMA compared nine treatments (including placebo). Donepezil (mean difference (MD)=1.41, 95% CI: 0.51 to 2.32) and donepezil +memantine (MD=2.57, 95% CI: 0.07 to 5.07) improved MMSE score (56 RCTs, 11 619 participants; CINeMA score: moderate) compared with placebo. According to P-score, oral rivastigmine (OR=1.26, 95% CI: 0.82 to 1.94, P-score=16%) and donepezil (OR=1.08, 95% CI: 0.87 to 1.35, P-score=30%) had the least favourable safety profile, but none of the estimated treatment effects were sufficiently precise when compared with placebo (45 RCTs, 15 649 patients; CINeMA score: moderate to high). For moderate-to-severe impairment, donepezil, memantine and their combination performed best, but for mild-to-moderate impairment donepezil and transdermal rivastigmine ranked best. Adjusting for MMSE baseline differences, oral rivastigmine and galantamine improved MMSE score, whereas when adjusting for comorbidities only oral rivastigmine was effective. CONCLUSIONS: The choice among the different cognitive enhancers may depend on patient's characteristics. The MDs of all cognitive enhancer regimens except for single-agent oral rivastigmine, galantamine and memantine, against placebo were clinically important for cognition (MD larger than 1.40 MMSE points), but results were quite imprecise. However, two-thirds of the published RCTs were associated with high risk of bias for incomplete outcome data, and IPD were only available for 15% of the included RCTs. PROSPERO REGISTRATION NUMBER: CRD42015023507.

Sharing individual participant data: through a systematic reviewer lens.

An increasing prevalence of data-sharing models, aimed at making individual participant data (IPD) from clinical trials widely available, should facilitate the conduct of systematic reviews and meta-analyses based on IPD. We have assessed these different data-sharing approaches, from the perspective of experienced IPD reviewers, to examine their utility for conducting systematic reviews based on IPD, and to highlight any challenges. We present an overview of the range of different models, including the traditional, single question approach, topic-based repositories, and the newer generic data platforms, and show that there are benefits and drawbacks to each. In particular, not all of the new models allow researchers to fully realise the well-documented advantages of using IPD for meta-analysis, and we offer potential solutions that can help improve both data quantity and utility. However, to achieve the "nirvana" of an ideal clinical data sharing environment, both for IPD meta-analysis and other secondary research purposes, we propose that data providers, data requestors, funders, and platforms need to adopt a more joined-up and standardised approach.

Coenzyme Q10 to manage chronic heart failure with a reduced ejection fraction: a systematic review and economic evaluation.

BACKGROUND: Chronic heart failure is a debilitating condition that accounts for an annual NHS spend of £2.3B. Low levels of endogenous coenzyme Q10 may exacerbate chronic heart failure. Coenzyme Q10 supplements might improve symptoms and slow progression. As statins are thought to block the production of coenzyme Q10, supplementation might be particularly beneficial for patients taking statins. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of coenzyme Q10 in managing chronic heart failure with a reduced ejection fraction. METHODS: A systematic review that included randomised trials comparing coenzyme Q10 plus standard care with standard care alone in chronic heart failure. Trials restricted to chronic heart failure with a preserved ejection fraction were excluded. Databases including MEDLINE, EMBASE and CENTRAL were searched up to March 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool (version 5.2). A planned individual participant data meta-analysis was not possible and meta-analyses were mostly based on aggregate data from publications. Potential effect modification was examined using meta-regression. A Markov model used treatment effects from the meta-analysis and baseline mortality and hospitalisation from an observational UK cohort. Costs were evaluated from an NHS and Personal Social Services perspective and expressed in Great British pounds at a 2019/20 price base. Outcomes were expressed in quality-adjusted life-years. Both costs and outcomes were discounted at a 3.5% annual rate. RESULTS: A total of 26 trials, comprising 2250 participants, were included in the systematic review. Many trials were reported poorly and were rated as having a high or unclear risk of bias in at least one domain. Meta-analysis suggested a possible benefit of coenzyme Q10 on all-cause mortality (seven trials, 1371 participants; relative risk 0.68, 95% confidence interval 0.45 to 1.03). The results for short-term functional outcomes were more modest or unclear. There was no indication of increased adverse events with coenzyme Q10. Meta-regression found no evidence of treatment interaction with statins. The base-case cost-effectiveness analysis produced incremental costs of £4878, incremental quality-adjusted life-years of 1.34 and an incremental cost-effectiveness ratio of £3650. Probabilistic sensitivity analyses showed that at thresholds of £20,000 and £30,000 per quality-adjusted life-year coenzyme Q10 had a high probability (95.2% and 95.8%, respectively) of being more cost-effective than standard care alone. Scenario analyses in which the population and other model assumptions were varied all found coenzyme Q10 to be cost-effective. The expected value of perfect information suggested that a new trial could be valuable. LIMITATIONS: For most outcomes, data were available from few trials and different trials contributed to different outcomes. There were concerns about risk of bias and whether or not the results from included trials were applicable to a typical UK population. A lack of individual participant data meant that planned detailed analyses of effect modifiers were not possible. CONCLUSIONS: Available evidence suggested that, if prescribed, coenzyme Q10 has the potential to be clinically effective and cost-effective for heart failure with a reduced ejection fraction. However, given important concerns about risk of bias, plausibility of effect sizes and applicability of the evidence base, establishing whether or not coenzyme Q10 is genuinely effective in a typical UK population is important, particularly as coenzyme Q10 has not been subject to the scrutiny of drug-licensing processes. Stronger evidence is needed before considering its prescription in the NHS. FUTURE WORK: A new independent, well-designed clinical trial of coenzyme Q10 in a typical UK heart failure with a reduced ejection fraction population may be warranted. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018106189. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 4. See the NIHR Journals Library website for further project information.

People living with chronic heart failure suffer from shortness of breath, ankle swelling, tiredness, frequent stays in hospital and reduced quality of life and have shorter lives. The NHS spends over £2 billion each year managing chronic heart failure. Coenzyme Q10 is a vitamin-like substance made by the body that helps cells produce energy. Low levels of coenzyme Q10 in heart muscle may lead to, or exacerbate, chronic heart failure. Taking coenzyme Q10 supplements might improve symptoms or slow deterioration. To the best of our knowledge, we found all randomised clinical trials of coenzyme Q10 in patients with the type of chronic heart failure caused by muscle weakness (i.e. heart failure with reduced ejection fraction, where the heart's pumping function is weaker than normal). We asked the research groups responsible for these trials to provide the patient data that they had collected in their trials. Most research groups did not share their data and so we mainly used information from published trial reports. This limited our planned analyses. We found that taking coenzyme Q10 alongside usual treatment for heart failure with reduced ejection fraction potentially reduced deaths by approximately one-third and reduced readmission to hospital by around 40%. However, these results were uncertain. Side effects were not increased. We had some concerns about how reliable the data were, and it is not clear how well the results apply to UK patients. We also worked out what the benefits and costs to the NHS would be if coenzyme Q10 became available on prescription for patients with heart failure with reduced ejection fraction. Our model found that prescription could be worthwhile; however, a new trial is needed first to make sure that coenzyme Q10 improves outcomes for patients. A new trial would be particularly important because coenzyme Q10 has not been assessed in the same way as prescribed medicines. A new trial could make sure that there is better evidence about whether or not prescribing would be a good use of NHS resources.

[The PRISMA 2020 statement: an updated guideline for reporting systematic reviewsDeclaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas]. / A declaração PRISMA 2020: diretriz atualizada para relatar revisões sistemáticas.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

La declaración PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), publicada en 2009, se diseñó para ayudar a los autores de revisiones sistemáticas a documentar de manera transparente el porqué de la revisión, qué hicieron los autores y qué encontraron. Durante la última década, ha habido muchos avances en la metodología y terminología de las revisiones sistemáticas, lo que ha requerido una actualización de esta guía. La declaración PRISMA 2020 sustituye a la declaración de 2009 e incluye una nueva guía de presentación de las publicaciones que refleja los avances en los métodos para identificar, seleccionar, evaluar y sintetizar estudios. La estructura y la presentación de los ítems ha sido modificada para facilitar su implementación. En este artículo, presentamos la lista de verificación PRISMA 2020 con 27 ítems, y una lista de verificación ampliada que detalla las recomendaciones en la publicación de cada ítem, la lista de verificación del resumen estructurado PRISMA 2020 y el diagrama de flujo revisado para revisiones sistemáticas.

Strengthening the clinical academic pathway: a systematic review of interventions to support clinical academic careers for doctors and dentists.

OBJECTIVE: Evaluate existing evidence on interventions intended to increase recruitment, retention and career progression within clinical academic (CA) careers, including a focus on addressing inequalities. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Cochrane Controlled Register of Trials, PsycINFO and Education Resource Information Center searched October 2019. STUDY SELECTION: Eligible studies included qualified doctors, dentists and/or those with a supervisory role. Outcomes were defined by studies and related to success rates of joining or continuing within a CA career. DATA EXTRACTION AND SYNTHESIS: Abstract screening was supported by machine learning software. Full-text screening was performed in duplicate, and study quality was assessed. Narrative synthesis of quantitative data was performed. Qualitative data were thematically analysed. RESULTS: 148 studies examined interventions; of which 28 were included in the quantitative synthesis, 17 in the qualitative synthesis and 2 in both. Studies lacked methodological rigour and/or were hindered by incomplete reporting. Most were from North America. No study included in the syntheses evaluated interventions aimed at CA dentists.Most quantitative evidence was from multifaceted training programmes. These may increase recruitment, but findings were less clear for retention and other outcomes. Qualitative studies reported benefits of supportive relationships, including peers and senior mentors. Protected time for research helped manage competing demands on CAs. Committed and experienced staff were seen as key facilitators of programme success. Respondents identified several other factors at a programme, organisational or national level which acted as facilitators or barriers to success. Few studies reported on the effects of interventions specific to women or minority groups. CONCLUSIONS: Existing research is limited by rigour and reporting. Better evaluation of future interventions, particularly those intended to address inequalities, is required. Within the limits of the evidence, comprehensive multifaceted programmes of training, including protected time, relational and support aspects, appear most successful in promoting CA careers. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework: https://osf.io/mfy7a.

A declaração PRISMA 2020: diretriz atualizada para relatar revisões sistemáticas / The PRISMA 2020 statement: an updated guideline for reporting systematic reviews / Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas

RESUMO A declaração dos Principais Itens para Relatar Revisões Sistemáticas e Meta-análises (PRISMA), publicada em 2009, foi desenvolvida para ajudar revisores sistemáticos a relatar de forma transparente por que a revisão foi feita, os métodos empregados e o que os autores encontraram. Na última década, os avanços na metodologia e terminologia de revisões sistemáticas exigiram a atualização da diretriz. A declaração PRISMA 2020 substitui a declaração de 2009 e inclui novas orientações para relato que refletem os avanços nos métodos para identificar, selecionar, avaliar e sintetizar estudos. A estrutura e apresentação dos itens foram modificadas para facilitar a implementação. Neste artigo, apresentamos a lista de checagem PRISMA 2020 de 27 itens, uma lista de checagem expandida que detalha as recomendações para relato para cada item, a lista de checagem PRISMA 2020 para resumos e os fluxogramas revisados para novas revisões e para atualização de revisões.

ABSTRACT The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

RESUMEN La declaración PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), publicada en 2009, se diseñó para ayudar a los autores de revisiones sistemáticas a documentar de manera transparente el porqué de la revisión, qué hicieron los autores y qué encontraron. Durante la última década, ha habido muchos avances en la metodología y terminología de las revisiones sistemáticas, lo que ha requerido una actualización de esta guía. La declaración PRISMA 2020 sustituye a la declaración de 2009 e incluye una nueva guía de presentación de las publicaciones que refleja los avances en los métodos para identificar, seleccionar, evaluar y sintetizar estudios. La estructura y la presentación de los ítems ha sido modificada para facilitar su implementación. En este artículo, presentamos la lista de verificación PRISMA 2020 con 27 ítems, y una lista de verificación ampliada que detalla las recomendaciones en la publicación de cada ítem, la lista de verificación del resumen estructurado PRISMA 2020 y el diagrama de flujo revisado para revisiones sistemáticas.

The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. / Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews. Full English text available from:www.revespcardiol.org/en.

Developing a topic-based repository of clinical trial individual patient data: experiences and lessons learned from a pilot project.

BACKGROUND: Building a dataset of individual participant data (IPD) for meta-analysis represents considerable research investment as well as collaboration across multiple institutions and researchers. Making arrangements to curate and share the dataset beyond the IPD meta-analysis project for which it was established, for reuse in future research projects, would maximise the value of this investment. METHODS: Our aim was to establish the Cochrane repository for individual patient data from clinical trials in pregnancy and childbirth (CRIB) as an example of how an IPD repository could become part of Cochrane infrastructure. We believed that establishing CRIB under Cochrane auspices would engender trust and encourage trial investigators to share data, and at the same time position Cochrane to take steps towards expanding the number of reviews with IPD synthesis. RESULTS: CRIB was designed as a web-based platform to receive, host and facilitate onward sharing of de-identified data. Development was not straightforward and we did not fully achieve our aim as intended. We describe the challenges encountered and suggest ways that future repositories might overcome these. In particular, securing the legal agreements required to facilitate data sharing proved to be the main barrier, being time-consuming and more complex than anticipated. CONCLUSIONS: We would recommend that researchers conducting IPD meta-analysis should consider discussing the option to transfer the curated IPD datasets to a repository at the end of the initial meta-analysis and this should be recognised within the data sharing agreements made with the original data contributors.

Top health research funders' guidance on selecting journals for funded research.

Background: Funded health research is being published in journals that many regard as "predatory", deceptive, and non-credible. We do not currently know whether funders provide guidance on how to select a journal in which to publish funded health research. Methods: We identified the largest 46 philanthropic, public, development assistance, public-private partnership, and multilateral funders of health research by expenditure, globally as well as four public funders from lower-middle income countries, from the list at https://healthresearchfunders.org. One of us identified guidance on disseminating funded research from each funders' website (August/September 2017), then extracted information about selecting journals, which was verified by another assessor. Discrepancies were resolved by discussion. Results were summarized descriptively. This research used publicly available information; we did not seek verification with funding bodies. Results: The majority (44/50) of sampled funders indicated funding health research. 38 (of 44, 86%) had publicly available information about disseminating funded research, typically called "policies" (29, 76%). Of these 38, 36 (95%) mentioned journal publication for dissemination of which 13 (36.11%) offer variable guidance on selecting a journal, all of which relate to the funder's open access mandate. Six funders (17%) outlined publisher requirements or features by which to select a journal. One funder linked to a document providing features of journals to look for (e.g. listed in the Directory of Open Access Journals) and to be wary of (e.g., no journal scope statement, uses direct and unsolicited marketing). Conclusions: Few funders provided guidance on how to select a journal in which to publish funded research. Funders have a duty to ensure that the research they fund is discoverable by others. This research is a benchmark for funder guidance on journal selection prior to the January 2021 implementation of Plan S (a global, funder-led initiative to ensure immediate, open access to funded, published research).

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.

The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.