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Background Systematic reviews of health interventions are increasingly incorporating evidence outside of randomized controlled trials (RCT). While non-randomized study (NRS) types may be more prone to bias compared to RCT, the tools used to evaluate risk of bias (RoB) in NRS are less straightforward and no gold standard tool exists. The objective of this study was to evaluate the planned use of RoB tools in systematic reviews of health interventions, specifically for reviews that planned to incorporate evidence from RCT and/or NRS. Methods We evaluated a random sample of non-Cochrane protocols for systematic reviews of interventions registered in PROSPERO between January 1 and October 12, 2018. For each protocol, we extracted data on the types of studies to be included (RCT and/or NRS) as well as the name and number of RoB tools planned to be used according to study design. We then conducted a longitudinal analysis of the most commonly reported tools in the random sample. Using keywords and name variants for each tool, we searched PROSPERO records by year since the inception of the database (2011 to December 7, 2018), restricting the keyword search to the “Risk of bias (quality) assessment” field. Results In total, 471 randomly sampled PROSPERO protocols from 2018 were included in the analysis. About two-thirds (63%) of these planned to include NRS, while 37% restricted study design to RCT or quasi-RCT. Over half of the protocols that planned to include NRS listed only a single RoB tool, most frequently the Cochrane RoB Tool. The Newcastle-Ottawa Scale and ROBINS-I were the most commonly reported tools for NRS (39% and 33% respectively) for systematic reviews that planned to use multiple RoB tools. Looking at trends over time, the planned use of the Cochrane RoB Tool and ROBINS-I seems to be increasing. Conclusions While RoB tool selection for RCT was consistent, with the Cochrane RoB Tool being the most frequently reported in PROSPERO protocols, RoB tools for NRS varied widely. Results suggest a need for more education and awareness on the appropriate use of RoB tools for NRS. Given the heterogeneity of study designs comprising NRS, multiple RoB tools tailored to specific designs may be required.

•Practical, evidence-informed advice considers the spectrum of public health science.•This framework fills a gap in the comprehensive development of vaccine guidance.•It enables the systematic examination of ethics, equity, feasibility, and acceptability.•In Canada, successful implementation has led to timely, transparent recommendations.•These tools, based on extensive research, can be used by advisory groups worldwide. For the successful implementation of population-level recommendations, it is critical to consider the full spectrum of public health science, including clinical and programmatic factors. Current frameworks may identify various factors that should be examined when making evidence-informed vaccine-related recommendations. However, while most immunization guidelines systematically assess clinical factors, such as efficacy and safety of vaccines, there is no published framework outlining how to systematically assess programmatic factors, such as the ethics, equity, feasibility, and acceptability of recommendations. We have addressed this gap with the development of the EEFA (Ethics, Equity Feasibility, Acceptability) Framework, supported by evidence-informed tools, including Ethics Integrated Filters, Equity Matrix, Feasibility Matrix, and an Acceptability Matrix. The Framework and tools are based on five years of environmental scans, systematic reviews and surveys, and refined by expert and stakeholder consultations and feedback. For each programmatic factor, the EEFA Framework summarizes the minimum threshold for consideration and when further in-depth analysis may be required, which aspects of the factor should be considered, how to assess the factor using the supporting evidence-informed tools, and who should be consulted to complete the assessment. Research, particularly in the fields of vaccine acceptability and equity, has validated the utility and comprehensiveness of the tools. The Framework has been successfully used in Canada for clear, timely, transparent vaccine guidance with positive stakeholder feedback on its comprehensiveness, relevance and appropriateness. Applying the EEFA Framework allows for the systematic consideration of the spectrum of public health science without a delay in recommendations, complementing existing decision-making frameworks. This Framework will therefore be useful for advisory groups worldwide to integrate critical factors that could impact the successful and timely implementation of comprehensive, transparent recommendations, and will further the global objective of developing practical and evidence-informed immunization policies.

Ismail et al offer a preliminary guidance for policy in key populations for early novel coronavirus disease 2019 (COVID-19) immunization. Alarming levels of spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the World Health Organization (WHO) to declare COVID-19 a pandemic on Mar 11, 2020. The pandemic is ongoing and has caused substantial morbidity and death, as well as social and economic disruption worldwide. Although the risk varies among and within communities, the risk to Canadians remains high. The goal of Canada's pandemic response is to minimize serious illness and deaths while minimizing societal disruption as a result of the pandemic. Infection prevention and control measures such as physical distancing have been critical to slow the spread of COVID-19. Immunization with a safe and effective vaccine could hasten the containment and control of disease with reduced morbidity and mortality, as has been accomplished with other vaccine preventable diseases for more than 50 years. Global efforts to develop a SARS-CoV-2 vaccine are progressing at an unprecedented pace and the Government of Canada is reviewing regulatory pathways to ensure rapid access to effective vaccines for Canadians without compromising vaccine safety.

•Immunocompromised patients are at increased risk for herpes zoster (HZ) and its complications.•The recombinant zoster vaccine (RZV) is indicated for prevention of HZ in adults aged ≥ 50 years.•Consolidated data show RZV has an acceptable safety profile in ≥ 18 y.o. immunocompromised patients.•No exacerbation of underlying diseases was observed in RZV groups’ as compared to placebo.•RZV efficacy against HZ in immunocompromised ≥ 18 y.o. patients varied between 67 and 87% The adjuvanted recombinant zoster vaccine (RZV) is indicated for prevention of herpes zoster (HZ) in adults aged ≥50 years. Questions regarding the use of RZV in immunocompromised patients < 50-year-old, who are at increased risk for HZ, were raised. The objective of this systematic review was to consolidate existing evidences on safety, immunogenicity and efficacy of RZV in immunocompromised adults aged 18–49 years. Four databases were searched. Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidelines were followed. Screening and classification of search items was performed using the web-based platform DistillerSR. The search identified 1389 potentially relevant records. Six studies fulfilled inclusion criteria. The proportion of patients aged 18–49 varied between 23 and 62%. Pain at injection site (98.6%) and fatigue (75.3%) were the most common adverse events. The proportion of patients reporting serious adverse events (SAEs) ranged between 8.1 and 30.8% in RZV and between 4.1 and 36.5% in placebo groups. SAEs deemed related to vaccination were reported in < 1% of patients in both RZV and placebo groups. The proportion of patients that experienced clinically significant underlying disease-related events ranged between 0.0 and 20.0% in RZV and 0.0 and 26.7% in placebo groups. The humoral and cell-mediated immune response rate ranged between 65.4 and 96.2% and 50.0–93.0%, respectively. Vaccine efficacy in hematopoietic stem cell transplant patients was 72% (95%CI, 39–88%) in 18–49-year-olds and 67% (95%CI, 53–78%) in ≥ 50-year-olds (median follow-up 21 months). Vaccine efficacy in ≥ 18-year-old patients with hematologic malignancies was estimated at 87.2% (95%CI, 44.3–98.6%) up to 13 months post-vaccination. Results suggest that RZV has an acceptable safety profile and induces immunity in an important proportion of ≥ 18-year-old immunocompromised patients. Longer follow-up studies are warranted to assess the duration of RZV induced immunity in immunocompromised patients.

The COVID-19 pandemic has exposed social inequities that rival biological inequities in disease exposure and severity. Merely identifying some inequities without understanding all of them can lead to harmful misrepresentations and deepening disparities. Applying an ‘equity lens’ to bring inequities into focus without a vision to extinguish them is short-sighted. Interventions to address inequities should be as diverse as the pluralistic populations experiencing them. We present the first validated equity framework applied to COVID-19 that sheds light on the full spectrum of health inequities, navigates their sources and intersections, and directs ethically just interventions. The Equity Matrix also provides a comprehensive map to guide surveillance and research in order to unveil epidemiological uncertainties of novel diseases like COVID-19, recognising that inequities may exist where evidence is currently insufficient. Successfully applied to vaccines in recent years, this tool has resulted in the development of clear, timely and transparent guidance with positive stakeholder feedback on its comprehensiveness, relevance and appropriateness. Informed by evidence and experience from other vaccine-preventable diseases, this Equity Matrix could be valuable to countries across the social gradient to slow the spread of SARS-CoV-2 by abating the spread of inequities. In the race to SARS-CoV-2 vaccines, this urgently needed roadmap can effectively and efficiently steer global leadership towards equitable allocation with diverse strategies for diverse inequities. Such a roadmap has been absent from discussions on managing the COVID-19 pandemic, and is critical for our passage out of it.

Health Canada recently authorized the RSVpreF pregnancy vaccine and nirsevimab to protect infants against respiratory syncytial virus (RSV) disease. Assess the cost-effectiveness of RSVpreF and nirsevimab programs in preventing RSV disease in infants, compared to a palivizumab program. We used a static cohort model of a Canadian birth cohort during their first RSV season to estimate sequential incremental cost-effectiveness ratios (ICERs) in 2023 Canadian dollars per quality-adjusted life year (QALY) for nine strategies implemented over a one-year time period, from the health system and societal perspectives. Sensitivity and scenario analyses were conducted to explore the impact of uncertainties on the results. All-infants nirsevimab programs averted more RSV-related outcomes than year-round RSVpreF programs, with the most RSV cases averted in a seasonal nirsevimab program with catch-up. Assuming list prices for these immunizing agents, all-infants nirsevimab and year-round RSVpreF programs were never cost-effective, with ICERs far exceeding commonly used cost-effectiveness thresholds. Seasonal nirsevimab with catch-up for infants born outside the RSV season was a cost-effective program if prioritized for infants at moderate/high-risk (ICER <$28,000 per QALY) or those living in settings with higher RSV burden and healthcare costs, such as remote communities where transport would be complex (ICER of $5700 per QALY). Using a $50,000 per QALY threshold, an all-infants nirsevimab program could be optimal if nirsevimab is priced at <$110–190 per dose. A year-round RSVpreF for all pregnant women and pregnant people plus nirsevimab for infants at high-risk was optimal if nirsevimab is priced at >$110–190 per dose and RSVpreF priced at <$60–125 per dose. Prophylactic interventions can substantially reduce RSV disease in infants, and more focused nirsevimab programs are the most cost-effective option at current product prices.

•>100 studies on vaccine acceptability among Canadians were published over 5 years.•The perceived safety and importance of the vaccine were common influential factors.•Vaccination history and a healthcare provider’s recommendation influenced uptake.•Reminder systems and policies that improve access may increase uptake and coverage. Canada's National Advisory Committee on Immunization (NACI) provides guidance on the use of vaccines in Canada. To support the expansion of its mandate to include considerations for vaccine acceptability when making recommendations, the NACI Secretariat developed a matrix of factors that influence acceptability. To inform and validate the matrix, we systematically reviewed evidence for factors that influence vaccine acceptability, and for interventions aimed at improving acceptability. On 10–11 October 2018 we searched four bibliographic databases, the Theses Canada Portal, and ClinicalTrials.gov. Two reviewers agreed on the included studies. From each study, we extracted information about the participants, intervention or exposure, comparator, and relevant outcomes. Due to heterogeneity in the reported factors and acceptability indicators we synthesized the findings narratively. We appraised the certainty of evidence using GRADE. For each vaccine-preventable disease we populated a matrix of factors for which there was evidence of an influence on acceptability. One hundred studies (>1 million participants) contributed data relevant to the public, 16 (6191 participants) to healthcare providers, and three (84 participants) to policymakers. There were 43 intervention studies (~2 million participants). Across vaccines, we identified low certainty evidence for 70 factors relevant to the general population, 56 to high-risk groups, and 30 to healthcare providers. The perceived safety and importance of the vaccine, vaccination history, and receiving a recommendation from a healthcare provider were common influential factors. We found low certainty evidence that reminders for childhood vaccines and policies or delivery models for rotavirus vaccines could improve uptake and coverage. Evidence for other interventions was of very low certainty. The NACI vaccine acceptability matrix is useful for categorizing acceptability factors for the general public. Reminder systems may improve the uptake of childhood vaccines. Policies that make the rotavirus vaccine universally available and easily accessible may improve coverage. This systematic review was completed under contract to the Public Health Agency of Canada, Contract #4600001536.

The National Advisory Committee on Immunization (NACI) makes recommendations for vaccines in Canada. To inform considerations for equity when making recommendations, the NACI Secretariat developed a matrix of factors that may influence vaccine equity. To inform the matrix we mapped the evidence for P2ROGRESS And Other factors potentially associated with unequal levels of illness or death from vaccine-preventable diseases (VPDs) and systematically reviewed the evidence for interventions aimed at reducing inequities. In October 2019 we searched Medline, Embase, and CINAHL. Two reviewers agreed on the included studies. Our primary outcomes were VPD-related hospitalizations and deaths. Secondary outcomes were differential vaccine access, and exposure, susceptibility, severity, and consequences of VPDs. Two reviewers appraised the certainty of evidence. We mapped the evidence for P2ROGRESS And Other factors and summarized the findings descriptively. We summarized the interventions narratively. We identified 413 studies reporting on P2ROGRESS And Other factors. The most commonly investigated factors included age (n = 374, 89%), pre-existing conditions (n = 179, 42%), and gender identity or sex (n = 144, 34%). We identified 2 trials investigating the effects of interventions. One (n = 1249) provided very low certainty evidence that staff vaccination policies may reduce hospitalizations and deaths from influenza among private care home residents. The other (n not reported) provided very low certainty evidence that universal vaccination by nurses in clinics may reduce hospitalizations for rotavirus gastroenteritis compared with vaccination by physicians or no intervention. There is a large body of studies reporting on hospitalizations and deaths from VPDs stratified by P2ROGRESS And Other factors. We found only two trials examining the effects of interventions on hospitalization for or mortality from VPDs. This review has been helpful to NACI and will be helpful to similar organizations aiming to systematically identify and target health inequities through the development of vaccine program recommendations.

ABSTRACTBackgroundRespiratory syncytial virus (RSV) vaccines could reduce disease burden and costs in older Canadian adults, but vaccination program cost-effectiveness is unknown. We evaluated the cost-effectiveness of different age cut-offs for RSV adult vaccination programs, with or without a focus on people with higher disease risk due to chronic medical conditions. MethodsWe developed a static individual-based model of medically attended RSV disease to compare alternative age-, medical risk–, and age-plus medical risk–based vaccination policies. The model followed a multiage population of 100 000 people aged 50 years and older. Vaccine characteristics were based on RSV vaccines authorized in Canada as of May 2024, with vaccine protection assumed to last 2 years (or 3 years in scenario analyses). We calculated sequential incremental cost-effectiveness ratios in 2023 Canadian dollars per quality-adjusted life year (QALY) from the health-system and societal perspectives, discounted at 1.5%. ResultsAlthough all vaccination strategies averted medically attended RSV disease, universal age-based strategies were not an efficient use of resources compared with medical risk–based strategies. Vaccinating adults aged 70 years and older with 1 or more chronic medical condition was the optimal strategy for a cost-effectiveness threshold of $50 000 per QALY. Results were sensitive to assumptions about vaccine price, but medical risk–based approaches remained optimal compared with age-based strategies, even when vaccine prices were low. Findings were robust to a range of alternative assumptions. InterpretationVaccination programs for RSV in some groups of older Canadians with underlying medical conditions are likely cost-effective. These findings can inform the design of vaccination programs.

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations and assist policy-makers in making evidence informed decisions. Systematic reviews (SRs) that summarize the available evidence on a specific topic are a valuable source of evidence in the development of such recommendations. However, conducting SRs requires significant human, time, and financial resources, which many NITAGs lack. Given that SRs already exist for many immunization-related topics, and to prevent duplication and overlap of reviews, a more practical approach may be for NITAGs to use existing SRs. Nevertheless, it can be challenging to identify relevant SRs, to select one SR from among multiple SRs, or to critically assess and effectively use them. To support NITAGs, the London School of Hygiene and Tropical Medicine, Robert Koch Institute and collaborators developed the SYSVAC project, which consists of an online registry of systematic reviews on immunization-related topics and an e-learning course, that supports the use of them (both freely accessible at https://www.nitag-resource.org/sysvac-systematic-reviews). Drawing from the e-learning course and recommendations from an expert panel, this paper outlines methods for using existing systematic reviews when making immunization-related recommendations. With specific examples and reference to the SYSVAC registry and other resources, it offers guidance on locating existing systematic reviews; assessing their relevance to a research question, up-to-dateness, and methodological quality and/or risk of bias; and considering the transferability and applicability of their findings to other populations or settings.