The Ottawa Statement implementation guidance document for cluster randomized trials in the hemodialysis setting.

Research teams are increasingly interested in using cluster randomized trial (CRT) designs to generate practice-guiding evidence for in-center maintenance hemodialysis. However, CRTs raise complex ethical issues. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, published in 2012, provides 15 recommendations to address ethical issues arising within 7 domains: justifying the CRT design, research ethics committee review, identifying research participants, obtaining informed consent, gatekeepers, assessing benefits and harms, and protecting vulnerable participants. But applying the Ottawa Statement recommendations to CRTs in the hemodialysis setting is complicated by the unique features of the setting and population. Here, with the help of content experts and patient partners, we co-developed this implementation guidance document to provide research teams, research ethics committees, and other stakeholders with detailed guidance on how to apply the Ottawa Statement recommendations to CRTs in the hemodialysis setting, the result of a 4-year research project. Thus, our work demonstrates how the voices of patients, caregivers, and all stakeholders may be included in the development of research ethics guidance.

Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Using an intersectionality lens to explore barriers and enablers to hepatitis C point-of-care testing: a qualitative study among people who inject drugs and service providers.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant global health burden, particularly among people who inject drugs. Rapid point-of-care HCV testing has emerged as a promising approach to improve HCV detection and linkage to care in harm reduction organizations such as needle and syringe programs. The objective of this study was to use an intersectionality lens to explore the barriers and enablers to point-of-care HCV testing in a needle and syringe program. METHODS: A qualitative study was conducted using semi-structured interviews with clients (people who inject drugs) and service providers in a large community organization focused on the prevention of sexually transmitted and blood borne infections and harm reduction in Montreal, Canada. An intersectionality lens was used alongside the Theoretical Domains Framework to guide the formulation of research questions as well as data collection, analysis, and interpretation. RESULTS: We interviewed 27 participants (15 clients, 12 providers). For clients, four themes emerged: (1) understanding and perceptions of HCV testing, (2) the role of an accessible and inclusive environment, (3) the interplay of emotions and motivations in decision-making, and (4) the impact of intersectional stigma related to HCV, behaviors, and identities. For providers, five themes emerged: (1) knowledge, skills, and confidence for HCV testing, (2) professional roles and their intersection with identity and lived experience, (3) resources and integration of services, (4) social and emotional factors, and (5) behavioral regulation and incentives for HCV testing. Intersectional stigma amplified access, emotional and informational barriers to HCV care for clients. In contrast, identity and lived experience acted as powerful enablers for providers in the provision of HCV care. CONCLUSION: The application of an intersectionality lens provides a nuanced understanding of multilevel barriers and enablers to point-of-care HCV testing. Findings underscore the need for tailored strategies that address stigma, improve provider roles and communication, and foster an inclusive environment for equitable HCV care. Using an intersectionality lens in implementation research can offer valuable insights, guiding the design of equity-focused implementation strategies.

One size doesn't fit all: methodological reflections in conducting community-based behavioural science research to tailor COVID-19 vaccination initiatives for public health priority populations.

BACKGROUND: Promoting the uptake of vaccination for infectious diseases such as COVID-19 remains a global challenge, necessitating collaborative efforts between public health units (PHUs) and communities. Applied behavioural science can play a crucial role in supporting PHUs' response by providing insights into human behaviour and informing tailored strategies to enhance vaccination uptake. Community engagement can help broaden the reach of behavioural science research by involving a more diverse range of populations and ensuring that strategies better represent the needs of specific communities. We developed and applied an approach to conducting community-based behavioural science research with ethnically and socioeconomically diverse populations to guide PHUs in tailoring their strategies to promote COVID-19 vaccination. This paper presents the community engagement methodology and the lessons learned in applying the methodology. METHODS: The community engagement methodology was developed based on integrated knowledge translation (iKT) and community-based participatory research (CBPR) principles. The study involved collaboration with PHUs and local communities in Ontario, Canada to identify priority groups for COVID-19 vaccination, understand factors influencing vaccine uptake and co-design strategies tailored to each community to promote vaccination. Community engagement was conducted across three large urban regions with individuals from Eastern European communities, African, Black, and Caribbean communities and low socioeconomic neighbourhoods. RESULTS: We developed and applied a seven-step methodology for conducting community-based behavioural science research: (1) aligning goals with system-level partners; (2) engaging with PHUs to understand priorities; (3) understanding community strengths and dynamics; (4) building relationships with each community; (5) establishing partnerships (community advisory groups); (6) involving community members in the research process; and (7) feeding back and interpreting research findings. Research partnerships were successfully established with members of prioritized communities, enabling recruitment of participants for theory-informed behavioural science interviews, interpretation of findings, and co-design of targeted recommendations for each PHU to improve COVID-19 vaccination uptake. Lessons learned include the importance of cultural sensitivity and awareness of sociopolitical context in tailoring community engagement, being agile to address the diverse and evolving priorities of PHUs, and building trust to achieve effective community engagement. CONCLUSION: Effective community engagement in behavioural science research can lead to more inclusive and representative research. The community engagement approach developed and applied in this study acknowledges the diversity of communities, recognizes the central role of PHUs, and can help in addressing complex public health challenges.

Developing a set of emergency department performance measures to evaluate delirium care quality for older adults: a modified e-Delphi study.

BACKGROUND: Older adults are at high risk of developing delirium in the emergency department (ED); however, it is under-recognized in routine clinical care. Lack of detection and treatment is associated with poor outcomes, such as mortality. Performance measures (PMs) are needed to identify variations in quality care to help guide improvement strategies. The purpose of this study is to gain consensus on a set of quality statements and PMs that can be used to evaluate delirium care quality for older ED patients. METHODS: A 3-round modified e-Delphi study was conducted with ED clinical experts. In each round, participants rated quality statements according to the concepts of importance and actionability, then their associated PMs according to the concept of necessity (1-9 Likert scales), with the ability to comment on each. Consensus and stability were evaluated using a priori criteria using descriptive statistics. Qualitative data was examined to identify themes within and across quality statements and PMs, which went through a participant validation exercise in the final round. RESULTS: Twenty-two experts participated, 95.5% were from west or central Canada. From 10 quality statements and 24 PMs, consensus was achieved for six quality statements and 22 PMs. Qualitative data supported justification for including three quality statements and one PM that achieved consensus slightly below a priori criteria. Three overarching themes emerged from the qualitative data related to quality statement actionability. Nine quality statements, nine structure PMs, and 14 process PMs are included in the final set, addressing four areas of delirium care: screening, diagnosis, risk reduction and management. CONCLUSION: Results provide a set of quality statements and PMs that are important, actionable, and necessary to a diverse group of clinical experts. To our knowledge, this is the first known study to develop a de novo set of guideline-based quality statements and PMs to evaluate the quality of delirium care older adults receive in the ED setting.

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.

Evidence for clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications among adults with peripheral artery disease: protocol for a systematic review and meta-analysis.

INTRODUCTION: International guidelines recommend that adults with peripheral artery disease (PAD) be prescribed antiplatelet, statin and antihypertensive medications. However, it is unclear how often people with PAD are underprescribed these drugs, which characteristics predict clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications, and whether underprescription and non-adherence are associated with adverse health and health system outcomes. METHODS AND ANALYSIS: We will search MEDLINE, EMBASE and Evidence-Based Medicine Reviews from 2006 onwards. Two investigators will independently review abstracts and full-text studies. We will include studies that enrolled adults and reported the incidence and/or prevalence of clinician underprescription of or patient non-adherence to guideline-recommended cardiovascular medications among people with PAD; adjusted risk factors for underprescription of/non-adherence to these medications; and adjusted associations between underprescription/non-adherence to these medications and outcomes. Outcomes will include mortality, major adverse cardiac and limb events (including revascularisation procedures and amputations), other reported morbidities, healthcare resource use and costs. Two investigators will independently extract data and evaluate study risk of bias. We will calculate summary estimates of the incidence and prevalence of clinician underprescription/patient non-adherence across studies. We will also conduct subgroup meta-analyses and meta-regression to determine if estimates vary by country, characteristics of the patients and treating clinicians, population-based versus non-population-based design, and study risks of bias. Finally, we will calculate pooled adjusted risk factors for underprescription/non-adherence and adjusted associations between underprescription/non-adherence and outcomes. We will use Grading of Recommendations, Assessment, Development and Evaluation to determine estimate certainty. ETHICS AND DISSEMINATION: Ethics approval is not required as we are studying published data. This systematic review will synthesise existing evidence regarding clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications in adults with PAD. Results will be used to identify evidence-care gaps and inform where interventions may be required to improve clinician prescribing and patient adherence to prescribed medications. PROSPERO REGISTRATION NUMBER: CRD42022362801.

Mailed feedback to primary care physicians on antibiotic prescribing for patients aged 65 years and older: pragmatic, factorial randomised controlled trial.

OBJECTIVES: To evaluate whether providing family physicians with feedback on their antibiotic prescribing compared with that of their peers reduces antibiotic prescriptions. To also identify effects on antibiotic prescribing from case-mix adjusted feedback reports and messages emphasising antibiotic associated harms. DESIGN: Pragmatic, factorial randomised controlled trial. SETTING: Primary care physicians in Ontario, Canada PARTICIPANTS: All primary care physicians were randomly assigned a group if they were eligible and actively prescribing antibiotics to patients 65 years or older. Physicians were excluded if had already volunteered to receive antibiotic prescribing feedback from another agency, or had opted out of the trial. INTERVENTION: A letter was mailed in January 2022 to physicians with peer comparison antibiotic prescribing feedback compared with the control group who did not receive a letter (4:1 allocation). The intervention group was further randomised in a 2x2 factorial trial to evaluate case-mix adjusted versus unadjusted comparators, and emphasis, or not, on harms of antibiotics. MAIN OUTCOME MEASURES: Antibiotic prescribing rate per 1000 patient visits for patients 65 years or older six months after intervention. Analysis was in the modified intention-to-treat population using Poisson regression. RESULTS: 5046 physicians were included and analysed: 1005 in control group and 4041 in intervention group (1016 case-mix adjusted data and harms messaging, 1006 with case-mix adjusted data and no harms messaging, 1006 unadjusted data and harms messaging, and 1013 unadjusted data and no harms messaging). At six months, mean antibiotic prescribing rate was 59.4 (standard deviation 42.0) in the control group and 56.0 (39.2) in the intervention group (relative rate 0.95 (95% confidence interval 0.94 to 0.96). Unnecessary antibiotic prescribing (0.89 (0.86 to 0.92)), prolonged duration prescriptions defined as more than seven days (0.85 (0.83 to 0.87)), and broad spectrum prescribing (0.94 (0.92 to 0.95)) were also significantly lower in the intervention group compared with the control group. Results were consistent at 12 months post intervention. No significant effect was seen for including emphasis on harms messaging. A small increase in antibiotic prescribing with case-mix adjusted reports was noted (1.01 (1.00 to 1.03)). CONCLUSIONS: Peer comparison audit and feedback letters significantly reduced overall antibiotic prescribing with no benefit of case-mix adjustment or harms messaging. Antibiotic prescribing audit and feedback is a scalable and effective intervention and should be a routine quality improvement initiative in primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04594200.

A declaração PRISMA 2020: diretriz atualizada para relatar revisões 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 metodo- logia 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 modifi- cadas 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 imple- mentation. 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.

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.