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Essential medicine lists (EMLs) are important medicine prioritization tools used by the World Health Organization (WHO) EML and over 130 countries. The criteria used by WHO's Expert Committee on the Selection and Use of Essential Medicines has parallels to the GRADE Evidence-to-Decision (EtD) frameworks. In this study, we explored the EtD frameworks and a visual abstract as adjunctive tools to strengthen the integrate evidence and improve the transparency of decisions of EML applications. We conducted user-experience testing interviews of key EML stakeholders using Morville's honeycomb model. Interviews explored multifaceted dimensions (e.g., usability) on two EML applications for the 2021 WHO EML-long-acting insulin analogues for diabetes and immune checkpoint inhibitors for lung cancer. Using a pre-determined coding framework and thematic analysis we iteratively improved both the EtD framework and the visual abstract. We coded the transcripts of 17 interviews with 13 respondents in 103 locations of the interview texts across all dimensions of the user-experience honeycomb. Respondents felt the EtD framework and visual abstract presented complementary useful and findable adjuncts to the traditional EML application. They felt this would increase transparency and efficiency in evidence assessed by EML committees. As EtD frameworks are also used in health practice guidelines, including those by the WHO, respondents articulated that the adoption of the EtD by EML applications represents a tangible mechanism to align EMLs and guidelines, decrease duplication of work and improve coordination. Improvements were made to clarify instructions for the EtD and visual abstract, and to refine the design and content included. 'Availability' was added as an additional criterion for EML applications to highlight this criterion in alignment with WHO EML criteria. EtD frameworks and visual abstracts present additional important tools to communicate evidence and support decision-criteria in EML applications, which have global health impact. Access to essential medicines is important for achieving universal health coverage, and the development of essential medicine lists should be as evidence-based and trustworthy as possible.

Introduction Intranasal antihistamines and corticosteroids are some of the most frequently used drug classes in the treatment of allergic rhinitis. However, there is uncertainty as to whether effectiveness differences may exist among different intranasal specific medications. This systematic review aims to analyse and synthesise all evidence from randomised controlled trials (RCTs) on the effectiveness of intranasal antihistamines and corticosteroids in rhinitis nasal and ocular symptoms and in rhinoconjunctivitis-related quality-of-life.Methods and analysis We will search four electronic bibliographic databases and three clinical trials databases for RCTs (1) assessing patients ≥12 years old with seasonal or perennial allergic rhinitis and (2) comparing the use of intranasal antihistamines or corticosteroids versus placebo. Assessed outcomes will include the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS) and the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. Certainty in the body of evidence for the analysed outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will perform a random-effects meta-analysis for each assessed medication and outcome, presenting results as pooled mean differences and standardised mean differences. Heterogeneity will be explored by sensitivity and subgroup analyses, considering (1) the risk of bias, (2) the follow-up period and (3) the drug dose.Ethics and dissemination Ethical considerations will not be required. Results will be disseminated in a peer-review journal.PROSPERO registration number CRD42023416573.

Objectives: Despite an extensive risk of exposure to COVID-19, the residents of Giglio Island, Italy, did not develop any symptom of SARS-CoV-2. The present study aims to characterize the nature of exposure and to describe the local population dynamics underlying its apparent resistance to COVID-19. Methods: Descriptive study of an islander partially-segregated population cohort based on a seroprevalence screening conducted from Aprile 29 to May 3, 2020 and including SARS-CoV-2 seroprevalence and viral prevalence in samples of saliva assessed through RT-qPCR. Serologic testing was performed using a COVID-19 IgG/IgM rapid test while molecular analyses were carried out by Allplex 2019-nCoV Assay (Seegene). Results: A total of 634 residents out of 748 (84.8%) present at the time, and 89 non-residents underwent serological testing. 364 males and 359 females with a median age of 58.5 years. The serological screening identified one positive, asymptomatic subject. The Nucleic Acid Amplification Tests (NAAT) did not yield any positive result. Conclusion: Despite extensive exposure to SARS-CoV-2, possibly only one new asymptomatic infection occurred in this population, as documented by IgM positivity not confirmed by RT-qPCR. This may be due to unknown protective factors or chance. On the basis of this baseline study, using its population as a reference model, further investigations will be conducted to test the advanced hypotheses, focusing on the evaluation of a possible cross-reactivity to SARS-CoV-2 from exposure to endemic viruses.

Summary: Clinicians, patients, policy makers, funders, programme managers, regulators, and science communities invest considerable amounts of time and energy in influencing or making decisions at various levels, using systematic reviews, health technology assessments, guideline recommendations, coverage decisions, selection of essential medicines and diagnostics, quality assurance and improvement schemes, and policy and evidence briefs. The criteria and methods that these actors use in their work differ (eg, the role economic analysis has in decision making), but these methods frequently overlap and exist together. Under the aegis of WHO, we have brought together representatives of different areas to reconcile how the evidence that influences decisions is used across multiple health system decision levels. We describe the overlap and differences in decision-making criteria between different actors in the health sector to provide bridging opportunities through a unifying broad framework that we call theory of everything. Although decision-making activities respond to system needs, processes are often poorly coordinated, both globally and on a country level. A decision made in isolation from other decisions on the same topic could cause misleading, unnecessary, or conflicted inputs to the health system and, therefore, confusion and resource waste.

Introduction The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and similar Evidence to Decision (EtD) frameworks require its users to judge how substantial the effects of interventions are on desirable and undesirable people-important health outcomes. However, decision thresholds (DTs) that could help understand the magnitude of intervention effects and serve as reference for interpretation of findings are not yet available.The objective of this study is an approach to derive and use DTs for EtD judgments about the magnitude of health benefits and harms. We hypothesise that approximate DTs could have the ability to discriminate between the existing four categories of EtD judgments (Trivial, Small, Moderate, Large), support panels of decision-makers in their work, and promote consistency and transparency in judgments.Methods and analysis We will conduct a methodological randomised controlled trial to collect the data that allow deriving the DTs. We will invite clinicians, epidemiologists, decision scientists, health research methodologists, experts in Health Technology Assessment (HTA), members of guideline development groups and the public to participate in the trial. Then, we will investigate the validity of our DTs by measuring the agreement between judgments that were made in the past by guideline panels and the judgments that our DTs approach would suggest if applied on the same guideline data.Ethics and dissemination The Hamilton Integrated Research Ethics Board reviewed this study as a quality improvement study and determined that it requires no further consent. Survey participants will be required to read a consent statement in order to participate in this study at the beginning of the trial. This statement reads: You are being invited to participate in a research project which aims to identify indicative DTs that could assist users of the GRADE EtD frameworks in making judgments. Your input will be used in determining these indicative thresholds. By completing this survey, you provide consent that the anonymised data collected will be used for the research study and to be summarised in aggregate in publication and electronic tools.PROTOCOL registration number NCT05237635.

Best practices for the dissemination of global health guidelines has not undergone rigorous research. We used a new approach to digitizing World Health Organization (WHO) global tuberculosis guideline recommendations (eTB RecMap) and compared its usability to the conventional method of accessing TB recommendations using the WHO website. We conducted a two-arm superiority randomised controlled trial using a survey among global stakeholders who were past or planned future users of TB guidelines, recommendations, or policy advice. We assigned participants randomly (1:1) to complete an activity using the WHO eTB RecMap or the conventional website. The primary outcome was the accessibility of information and secondary outcomes understanding, satisfaction, and preference for one of the two formats. Between February 26 and August 29, 2021, we received 478 responses from stakeholders, of whom 244 (122 per group) were eligible and provided analysable results. Participants rated the eTB RecMap as more accessible, on average, when compared to the conventional website (on a seven-point scale, the mean difference {MD} was 0.9; 95% confidence interval {CI}: 0.6, 1.2; p < 0.001) and were more likely to correctly answer understanding questions. This is the first trial comparing digitized dissemination formats of health guideline recommendations. Stakeholders rated the WHO eTB RecMap as more accessible than the conventional WHO website for the tested recommendations. They also understood presented information better. The findings support better usability of TB information through the eTB RecMap and contribute to the effort to end the TB epidemic. Trial registration: This trial was registered with ClinicalTrials.gov (NCT04745897) on February 9, 2021.

Introduction Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies.Methods We searched five general, three Chinese and four coronavirus disease (COVID-19)–specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments.Results We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps.Conclusion While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.

Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology is used to assess and report certainty of evidence and strength of recommendations. This GRADE concept article is not GRADE guidance but introduces certainty of net benefit, defined as the certainty that the balance between desirable and undesirable health effects is favourable. Determining certainty of net benefit requires considering certainty of effect estimates, the expected importance of outcomes and variability in importance, and the interaction of these concepts. Certainty of net harm is the certainty that the net effect is unfavourable. Guideline panels using or testing this approach might limit strong recommendations to actions with a high certainty of net benefit or against actions with a moderate or high certainty of net harm. Recommendations may differ in direction or strength from that suggested by the certainty of net benefit or harm when influenced by cost, equity, acceptability or feasibility.

Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only relevant or controlled data and directly inform clinical management decisions. Systematic reviews and meta-analyses are important tools to provide robust and informative evidence summaries of these animal studies. Rating how certain we are about the evidence could provide important information about the translational probability of findings in experimental animal studies to clinical practice and probably improve it. Evidence summaries and certainty in the evidence ratings could also be used (1) to support selection of interventions with best therapeutic potential to be tested in clinical trials, (2) to justify a regulatory decision limiting human exposure (to drug or toxin), or to (3) support decisions on the utility of further animal experiments. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is the most widely used framework to rate the certainty in the evidence and strength of health care recommendations. Here we present how the GRADE approach could be used to rate the certainty in the evidence of preclinical animal studies in the context of therapeutic interventions. We also discuss the methodological challenges that we identified, and for which further work is needed. Examples are defining the importance of consistency within and across animal species and using GRADE's indirectness domain as a tool to predict translation from animal models to humans.

Introduction Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits.Methods and analysis First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials.Ethics and dissemination Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings.Trial registration number PROSPERO CRD42013003526.

To develop guidance on what information to include and how to present it in tables summarizing the evidence from systematic reviews of test accuracy following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.To design and refine the evidence tables, we used an iterative process based on the analysis of data from four rounds of discussions, feedback and user testing. During the final round, we conducted one-on-one user testing with target end users. We presented a number of alternative formats of evidence tables to participants and obtained information about users' understanding and preferences.More than 150 users participated in initial discussions and provided their formal and informal feedback. 20 users completed one-on-one user testing interviews. Almost all participants preferred summarizing the results of systematic reviews of test accuracy in tabular format rather than plain text. Users generally preferred less complex tables but found presenting sensitivity and specificity estimates only as too simplistic. Users found the presentation of test accuracy for several values of prevalence initially confusing but modifying table layout and adding sample clinical scenarios for each prevalence reduced this confusion. Providing information about clinical consequences of testing result was viewed as not feasible for authors of systematic reviews.We present the current formats for tables presenting test accuracy following the GRADE approach. These tables can be developed using GRADEpro guidelines development tool (www.guidelinedevelopment.org or www.gradepro.org) and are being further developed into electronic interactive tables that will suit the needs of different end users. The formatting of these tables, and how they influence result interpretation and decision-making will be further evaluated in a randomized trial.

Background Prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20–30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.Objective The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy.Methods We identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations.Results Currently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence.Conclusions WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants. Keywords: Allergy, Prevention, Probiotics, Practice guidelines, GRADE

Use of antiretroviral therapy (ART) during treatment of drug susceptible tuberculosis (TB) improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR) 3.4, 95% CI 1.6-7.4) and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6) during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3) and less than 50 cells/mm(3), and when correcting for drug resistance pattern.We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

BACKGROUND: The response rates to physician postal surveys remain modest. The primary objective of this study was to assess the effect of tracking responses on physician survey response rate (i.e., determining whether each potential participant has responded or not). A secondary objective was to assess the effects of day of mailing (Monday vs. Friday) on physician survey response rate. METHODS: We conducted 3 randomized controlled trials. The first 2 trials had a 2 x 2 factorial design and tested the effect of day of mailing (Monday vs. Friday) and of tracking vs. no tracking responses. The third trial tested the effect of day of mailing (Monday vs. Friday). We meta-analyzed these 3 trials using a random effects model. RESULTS: The total number of participants in the 3 trials was 1339. The response rate with tracked mailing was not statistically different from that with non-tracked mailing by the time of the first reminder (RR = 1.01 95% CI 0.84, 1.22; I² = 0%). There was a trend towards lower response rate with tracked mailing by the time of the second reminder (RR = 0.91; 95% CI 0.78, 1.06; I² = 0%). The response rate with mailing on Mondays was not statistically different from that with Friday mailing by the time of first reminder (RR = 1.01; 95% CI 0.87, 1.17; I² = 0%), and by the time of the 2(nd) reminder (RR = 1.08; 95% CI 0.84, 1.39; I² = 77%). CONCLUSIONS: Tracking response may negatively affect physicians' response rate. The day of mailing does not appear to affect physicians' response rate.

BACKGROUND: Overactive bladder (OAB) affects the lives of millions of people worldwide and antimuscarinics are the pharmacological treatment of choice. Meta-analyses of all currently used antimuscarinics for treating OAB found similar efficacy, making the choice dependent on their adverse event profiles. However, conventional meta-analyses often fail to quantify and compare adverse events across different drugs, dosages, formulations, and routes of administration. In addition, the assessment of the broad variety of adverse events is dissatisfying. Our aim was to compare adverse events of antimuscarinics using a network meta-analytic approach that overcomes shortcomings of conventional analyses. METHODS: Cochrane Incontinence Group Specialized Trials Register, previous systematic reviews, conference abstracts, book chapters, and reference lists of relevant articles were searched. Eligible studies included randomized controlled trials comparing at least one antimuscarinic for treating OAB with placebo or with another antimuscarinic, and adverse events as outcome measures. Two authors independently extracted data. A network meta-analytic approach was applied allowing for joint assessment of all adverse events of all currently used antimuscarinics while fully maintaining randomization. RESULTS: 69 trials enrolling 26'229 patients were included. Similar overall adverse event profiles were found for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride but not for oxybutynin orally administered when currently used starting dosages were compared. CONCLUSIONS: The proposed generally applicable transparent network meta-analytic approach summarizes adverse events in an easy to grasp way allowing straightforward benchmarking of antimuscarinics for treating OAB in clinical practice. Most currently used antimuscarinics seem to be equivalent first choice drugs to start the treatment of OAB except for oral oxybutynin dosages of ≥ 10 mg/d which may have more unfavorable adverse event profiles.

BACKGROUND: We conducted an Internet-based randomized trial comparing three valence framing presentations of the benefits of antihypertensive medication in preventing cardiovascular disease (CVD) for people with newly diagnosed hypertension to determine which framing presentation resulted in choices most consistent with participants' values. METHODS AND FINDINGS: In this second in a series of televised trials in cooperation with the Norwegian Broadcasting Company, adult volunteers rated the relative importance of the consequences of taking antihypertensive medication using visual analogue scales (VAS). Participants viewed information (or no information) to which they were randomized and decided whether or not to take medication. We compared positive framing over 10 years (the number escaping CVD per 1000); negative framing over 10 years (the number that will have CVD) and negative framing per year over 10 years of the effects of antihypertensive medication on the 10-year risk for CVD for a 40 year-old man with newly diagnosed hypertension without other risk factors. Finally, all participants were shown all presentations and detailed patient information about hypertension and were asked to decide again. We calculated a relative importance score (RIS) by subtracting the VAS-scores for the undesirable consequences of antihypertensive medication from the VAS-score for the benefit of CVD risk reduction. We used logistic regression to determine the association between participants' RIS and their choice. 1,528 participants completed the study. The statistically significant differences between the groups in the likelihood of choosing to take antihypertensive medication in relation to different values (RIS) increased as the RIS increased. Positively framed information lead to decisions most consistent with those made by everyone for the second, more fully informed decision. There was a statistically significant decrease in deciding to take antihypertensives on the second decision, both within groups and overall. CONCLUSIONS: For decisions about taking antihypertensive medication for people with a relatively low baseline risk of CVD (70 per 1000 over 10 years), both positive and negative framing resulted in significantly more people deciding to take medication compared to what participants decided after being shown all three of the presentations. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register ISRCTN 33771631.

BackgroundWhile different ways of presenting treatment effects can affect health care decisions, little is known about which presentations best help people make decisions consistent with their own values. We compared six summary statistics for communicating coronary heart disease (CHD) risk reduction with statins: relative risk reduction and five absolute summary measures-absolute risk reduction, number needed to treat, event rates, tablets needed to take, and natural frequencies.Methods and findingsWe conducted a randomized trial to determine which presentation resulted in choices most consistent with participants' values. We recruited adult volunteers who participated through an interactive Web site. Participants rated the relative importance of outcomes using visual analogue scales (VAS). We then randomized participants to one of the six summary statistics and asked them to choose whether to take statins based on this information. We calculated a relative importance score (RIS) by subtracting the VAS scores for the downsides of taking statins from the VAS score for CHD. We used logistic regression to determine the association between participants' RIS and their choice. 2,978 participants completed the study. Relative risk reduction resulted in a 21% higher probability of choosing to take statins over all values of RIS compared to the absolute summary statistics. This corresponds to a number needed to treat (NNT) of 5; i.e., for every five participants shown the relative risk reduction one additional participant chose to take statins, compared to the other summary statistics. There were no significant differences among the absolute summary statistics in the association between RIS and participants' decisions whether to take statins. Natural frequencies were best understood (86% reported they understood them well or very well), and participants were most satisfied with this information.ConclusionsPresenting the benefits of taking statins as a relative risk reduction increases the likelihood of people accepting treatment compared to presenting absolute summary statistics, independent of the relative importance they attach to the consequences. Natural frequencies may be the most suitable summary statistic for presenting treatment effects, based on self-reported preference, understanding of and satisfaction with the information, and confidence in the decision.Clinical trials registrationISRCTN85194921.

BACKGROUND: We conducted an Internet-based randomized trial comparing four graphical displays of the benefits of antibiotics for people with sore throat who must decide whether to go to the doctor to seek treatment. Our objective was to determine which display resulted in choices most consistent with participants' values. METHODS AND FINDINGS: This was the first of a series of televised trials undertaken in cooperation with the Norwegian Broadcasting Company. We recruited adult volunteers in Norway through a nationally televised weekly health program. Participants went to our Web site and rated the relative importance of the consequences of treatment using visual analogue scales (VAS). They viewed the graphical display (or no information) to which they were randomized and were asked to decide whether to go to the doctor for an antibiotic prescription. We compared four presentations: face icons (happy/sad) or a bar graph showing the proportion of people with symptoms on day three with and without treatment, a bar graph of the average duration of symptoms, and a bar graph of proportion with symptoms on both days three and seven. Before completing the study, all participants were shown all the displays and detailed patient information about the treatment of sore throat and were asked to decide again. We calculated a relative importance score (RIS) by subtracting the VAS scores for the undesirable consequences of antibiotics from the VAS score for the benefit of symptom relief. We used logistic regression to determine the association between participants' RIS and their choice. 1,760 participants completed the study. There were statistically significant differences in the likelihood of choosing to go to the doctor in relation to different values (RIS). Of the four presentations, the bar graph of duration of symptoms resulted in decisions that were most consistent with the more fully informed second decision. Most participants also preferred this presentation (38%) and found it easiest to understand (37%). Participants shown the other three presentations were more likely to decide to go to the doctor based on their first decision than everyone based on the second decision. Participants preferred the graph using faces the least (14.4%). CONCLUSIONS: For decisions about going to the doctor to get antibiotics for sore throat, treatment effects presented by a bar graph showing the duration of symptoms helped people make decisions more consistent with their values than treatment effects presented as graphical displays of proportions of people with sore throat following treatment. CLINICAL TRIALS REGISTRATION: ISRCTN58507086.

Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.

Background: While the PRISMA flow diagram is widely used for reporting standard systematic reviews (SRs), it was not designed for capturing the results of continual searches for studies in living systematic reviews (LSRs). The objectives of this study are (1) to assess how published LSRs report on the flow of studies through the different phases of the review for the different updates; (2) to propose an approach to reporting on that flow. Methods: For objective 1, we identified all LSRs published up to April 2021. We abstracted information regarding their general characteristics and how they reported on search results. For objective 2, we based our proposal for tailored PRISMA approaches on the findings from objective 1, as well as on our experience with conducting Cochrane LSRs. Results: We identified 279 living publications relating to 76 LSRs. Of the 279 publications, 11% were protocols, 23% were base versions (i.e., the first version), 50% were partial updates (i.e., does not include all typical sections of an SR), and 16% were full updates (i.e., includes all typical sections of an SR). We identified six ways to reporting the study flow: base separately, each update separately (38%); numbers not reported (32%); latest update separately, all previous versions combined (20%); base separately, all updates combined (7%); latest update version only (3%); all versions combined (0%). We propose recording in detail the results of the searches to keep track of all identified records. For structuring the flow diagram, we propose using one of four approaches. Conclusion: We identified six ways for reporting the study flow through the different phases of the review for the different update versions. We propose to document in detail the study flow for the different search updates and select one of our four tailored PRISMA diagram approaches to present that study flow.

Background: While the PRISMA flow diagram is widely used for reporting standard systematic reviews (SRs), it was not designed for capturing the results of continual searches for studies in living systematic reviews (LSRs). The objectives of this study are (1) to assess how published LSRs report on the flow of studies through the different phases of the review for the different updates; (2) to propose an approach to reporting on that flow. Methods: For objective 1, we identified all LSRs published up to July 2020. We abstracted information regarding their general characteristics and how they reported on search results. For objective 2, we based our proposal for tailored PRISMA approaches on the findings from objective 1, as well as on our experience with conducting Cochrane LSRs. Results: We identified 108 living publications relating to 32 LSRs. Of the 108 publications, 7% were protocols, 24% were base versions (i.e., the first version), 62% were partial updates (i.e., does not include all typical sections of an SR), and 7% were full updates (i.e., includes all typical sections of an SR). We identified six ways to reporting the study flow: base separately, each update separately (38%); numbers not reported (32%); latest update separately, all previous versions combined (20%); base separately, all updates combined (7%); latest update version only (3%); all versions combined (0%). We propose recording in detail the results of the searches to keep track of all identified records. For structuring the flow diagram, we propose using one of four approaches. Conclusion: We identified six ways for reporting the study flow through the different phases of the review for the different update versions. We propose to document in detail the study flow for the different search updates and select one of our four tailored PRISMA diagram approaches to present that study flow.

Background: While the PRISMA flow diagram is widely used for reporting standard systematic reviews (SRs), it was not designed for capturing the results of continual searches for studies in living systematic reviews (LSRs). The objectives of this study are (1) to assess how published LSRs report on the flow of studies through the different phases of the review for the different updates; (2) to propose an approach to reporting on that flow. Methods: For objective 1, we identified all LSRs published up to July 2020. We abstracted information regarding their general characteristics and how they reported on search results. For objective 2, we based our proposal for tailored PRISMA approaches on the findings from objective 1, as well as on our experience with conducting Cochrane LSRs. Results: We identified 108 living publications relating to 32 LSRs. Of the 108 publications, 7% were protocols, 24% were base versions (i.e., the first version), 62% were partial updates (i.e., does not include all typical sections of an SR), and 7% were full updates (i.e., includes all typical sections of an SR). We identified six ways to reporting the study flow: base separately, each update separately (38%); numbers not reported (32%); latest update separately, all previous versions combined (20%); base separately, all updates combined (7%); latest update version only (3%); all versions combined (0%). We propose recording in detail the results of the searches to keep track of all identified records. For structuring the flow diagram, we propose using one of four approaches. Conclusion: We identified six ways for reporting the study flowthrough the different phases of the review for the different update versions. We propose to document in detail the study flow for the different search updates and select one of our four tailored PRISMA diagram approaches to present that study flow.

Background: The living systematic review (LSR) is an emerging approach for improved evidence synthesis that uses continual updating to include relevant new evidence as soon as it is published. The objectives of this study are to: 1) assess the methods of conduct and reporting of living systematic reviews using a living study approach; and 2) describe the life cycle of living systematic reviews, i.e., describe the changes over time to their methods and findings. Methods: For objective 1, we will begin by conducting a cross-sectional survey and then update its findings every 6 months by including newly published LSRs. For objective 2, we will conduct a prospective longitudinal follow-up of the cohort of included LSRs. To identify LSRs, we will continually search the following electronic databases: Medline, EMBASE and the Cochrane library. We will also contact groups conducting LSRs to identify eligible studies that we might have missed. We will follow the standard systematic review methodology for study selection and data abstraction. For each LSR update, we will abstract information on the following: 1) general characteristics, 2) systematic review methodology, 3) living approach methodology, 4) results, and 5) editorial and publication processes. We will update the findings of both the surveys and the longitudinal follow-up of included LSRs every 6 months. In addition, we will identify articles addressing LSR methods to be included in an ‘LSR methods repository’. Conclusion: The proposed living methodological survey will allow us to monitor how the methods of conduct, and reporting as well as the findings of LSRs change over time. Ultimately this should help with ensuring the quality and transparency of LSRs.

Background: The living systematic review (LSR) is an emerging approach for improved evidence synthesis that uses continual updating to include relevant new evidence as soon as it is published. The objectives of this study are to: 1) assess the methods of conduct and reporting of living systematic reviews using a living study approach; and 2) describe the life cycle of living systematic reviews, i.e., describe the changes over time to their methods and findings. Methods: For objective 1, we will begin by conducting a cross-sectional survey and then update its findings every 6 months by including newly published LSRs. For objective 2, we will conduct a prospective longitudinal follow-up of the cohort of included LSRs. To identify LSRs, we will continually search the following electronic databases: Medline, EMBASE and the Cochrane library. We will also contact groups conducting LSRs to identify eligible studies that we might have missed. We will follow the standard systematic review methodology for study selection and data abstraction. For each LSR update, we will abstract information on the following: 1) general characteristics, 2) systematic review methodology, 3) living approach methodology, 4) results, and 5) editorial and publication processes. We will update the findings of both the surveys and the longitudinal follow-up of included LSRs every 6 months. In addition, we will identify articles addressing LSR methods to be included in an ‘LSR methods repository’. Conclusion: The proposed living methodological survey will allow us to monitor how the methods of conduct, and reporting as well as the findings of LSRs change over time. Ultimately this should help with ensuring the quality and transparency of LSRs.