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The first version of the World Health Organization Model list of essential medicines contained 186 medicines in 1977 and has evolved to include 502 medicines in 2023. Over time, different articles criticized the methods and process for decisions; however, the list holds global relevance as a model list to over 150 national lists. Given the global use of the model list, reflecting on its future role is imperative to understand how the list should evolve and respond to the needs of Member States. In 2023, the model list Expert Committee recommended the World Health Organization (WHO) to initiate a process to revise the procedures for updating the model list and the criteria guiding decisions. Here, we offer an agenda outlining priority areas and a vision for an authoritative model list. The main areas include improving transparency and trustworthiness of the recommendations; strengthening connection to national lists; and continuing the debate on the principles that should guide the model list, in particular the role of cost and price of essential medicines. These reflections are intended to support efforts ensuring the continued impact of this policy tool., Competing Interests: Governments are paying increased attention to conflicts of interest, and applications to the model list may come from those with vested financial interests.32 Indeed, companies’ global market strategy may drive their desire to apply to the model list. The challenge lies in ensuring that interest is adequately managed so that the expert committee can decide on unbiased available evidence. Equally, attention to conflicts of interest among the committee’s members is critical to ensuring robust, defensible and trustworthy WHO recommendations. When selecting essential medicines, the committee’s experts can learn from WHO’s guideline recommendation development process, where in response to criticism, a process to overhaul the management of interests was implemented, mitigating risks of undue influence.33,34 However, even the introduction of detailed disclosure forms for WHO experts and strong mitigation strategies may not completely avoid risks of actual or perceived interests and biases. For example, in 2019, concerns about perceived experts’ conflicts of interest were among the reasons to discontinue two WHO guidelines on opioid use.35 While identifying and managing obvious, direct conflicts of interest in the model list process is possible, for example the exclusion of an expert who has received payments from a pharmaceutical industry, mechanisms to identify and manage indirect and less obvious conflicts of interest are more challenging, such as the influence of pervasive pharmaceutical marketing on forming an expert opinion., ((c) 2024 The authors; licensee World Health Organization.)

The World Health Organization (WHO) plays an important role in developing evidence-based and ethically sound guidelines to assist health workers, programme managers and policy-makers, particularly in countries with limited capacities to create their own. While the development of these guidelines follows rigorous methods, contextualizing recommendations is often necessary to ensure their applicability, feasibility and acceptability at the country level. The adaptation and adoption of global guidelines should happen in a transparent, systematic and participatory manner to maintain credibility while ensuring the ownership necessary for implementation. Here, we present an example from Estonia that showcases the process, requirements and outcomes of implementing WHO guidelines through effective contextualization. The work in Estonia showed that contextualization can shorten guideline development time and reduce costs. To support countries in contextualizing guidelines, including those developed by WHO, to local contexts while maintaining trustworthiness and relevance, the WHO Regional Office for Europe has developed a handbook based on the GRADE-Adolopment approach to guide this process. Furthermore, a rapid assessment of 21 of the 53 Member States in the WHO European Region revealed that many countries need guidance and support to build capacity for contextualizing guidelines. To address the capacity gaps, we suggest a way forward that encompasses four areas of further work: standardizing methods; institutionalizing guideline programmes and initiatives; promoting continuous and shared learning; and providing support and identifying resources. Strengthening countries' capacities to contextualize global guidelines is crucial and will become especially relevant during future health threats, such as pandemics, climate change and conflict situations., ((c) 2024 The authors; licensee World Health Organization.)

Background: Low- and middle-income countries adapt World Health Organization (WHO) guidelines instead of de novo development for financial, epidemiologic, sociopolitical, cultural, organizational, and other reasons., Objective: To systematically evaluate reported processes used in the adaptation of WHO guidelines for human immunodeficiency virus (HIV) and tuberculosis (TB)., Methods: We searched three online databases/repositories: United States Agency for International Development (USAID) AIDS Support and Technical Resources - Sector One program (AIDSTAR-One) National Treatment Database; the AIDSspace Guideline Repository, and WHO Database of national HIV and TB guidelines. We assessed the rigor and quality of reported adaptation methodology using the ADAPTE process as benchmark., Results: Of 170 eligible guidelines, only 32 (19%) reported documentation on the adaptation process. The median and interquartile range of the number of ADAPTE steps fulfilled by the eligible guidelines were 11.5 (10, 13.5) (out of 23 steps). The number of guidelines (out of 32 steps) fulfilling each ADAPTE step was 18 (interquartile range, 5-27). Seventeen of 32 guidelines (53%) met all steps relevant to the setup phase, whereas none met all steps relevant to the adaptation phase., Conclusion: The number of well-documented adaptation methodologies in national HIV and/or TB guidelines is very low. There is a need for the use of standardized and systematic framework for guideline adaptation and improved reporting of processes used., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: In 2007 the World Health Organization (WHO) adopted the GRADE system for development of public health guidelines. Previously we found that many strong recommendations issued by WHO are based on evidence for which there is only low or very low confidence in the estimates of effect (discordant recommendations). GRADE guidance indicates that such discordant recommendations are rarely appropriate but suggests five paradigmatic situations in which discordant recommendations may be warranted. We sought to provide insight into the many discordant recommendations in WHO guidelines., Study Design and Setting: We examined all guidelines that used the GRADE method and were approved by the WHO Guideline Review Committee between 2007 and 2012. Teams of reviewers independently abstracted data from eligible guidelines and classified recommendations either into one of the five paradigms for appropriately-formulated discordant recommendations or into three additional categories in which discordant recommendations were inconsistent with GRADE guidance: 1) the evidence warranted moderate or high confidence (a misclassification of evidence) rather than low or very low confidence; 2) good practice statements; or 3) uncertainty in the estimates of effect would best lead to a conditional (weak) recommendation., Results: The 33 eligible guidelines included 160 discordant recommendations, of which 98 (61.3%) addressed drug interventions and 132 (82.5%) provided some rationale (though not entirely explicit at times) for the strong recommendation. Of 160 discordant recommendations, 25 (15.6%) were judged consistent with one of the five paradigms for appropriate recommendations; 33 (21%) were based on evidence warranting moderate or high confidence in the estimates of effect; 29 (18%) were good practice statements; and 73 (46%) warranted a conditional, rather than a strong recommendation., Conclusion: WHO discordant recommendations are often inconsistent with GRADE guidance, possibly threatening the integrity of the process. Further training in GRADE methods for WHO guideline development group members may be necessary, along with further research on what motivates the formulation of such recommendations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3., Methods: Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel., Results: There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization., Conclusion: Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background: The World Health Organization (WHO) classifies a substantial proportion of their recommendations as strong despite low or very low confidence (certainty) in estimates of effect. Such discordant recommendations are often inconsistent with Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance., Objective: To gain the perspective of senior WHO methodology chairs regarding panels' use of GRADE, particularly regarding discordant recommendations., Data Sources: Senior active GRADE methodologists who had served on at least two WHO panels and were an author on at least one peer-reviewed published article on GRADE methodology., Methods: Five eligible methodologists participated in detailed semistructured interviews. Respondents answered questions regarding how they were viewed by other panelists and WHO leadership, and how they handled situations when panelists made discordant recommendations they felt were inappropriate. They also provided information on how the process can be improved. Interviews were recorded and transcribed, and inductive content analysis was used to derive codes, categories, and emergent themes., Results: Three themes emerged from the interviews of five methodologists: (1) The perceived role of methodologists in the process, (2) Contributors to discordant recommendations, and (3) Strategies for improvement. Salient findings included (1) a perceived tension between methodologists and WHO panels as a result of panel members' resistance to adhering to GRADE guidance; (2) both financial and nonfinancial conflicts of interest among panel members as an explanation for discordant recommendations; and (3) the need for greater clarity of, and support for, the role of methodologists as co-chairs of panels., Conclusions: These findings suggest that the role of the GRADE methodologist as a co-chair needs to be clarified by the WHO leadership. They further suggest the need for additional training for panelists, quality monitoring, and feedback to ensure optimal use of GRADE in guideline development at WHO., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Many strong recommendations issued by the World Health Organization (WHO) are based on low- or very low-quality (low certainty) evidence (discordant recommendations). Many such discordant recommendations are inconsistent with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We sought to understand why WHO makes discordant recommendations inconsistent with GRADE guidance., Study Design and Setting: We interviewed panel members involved in guidelines approved by WHO (2007-2012) that included discordant recommendations. Interviews, recorded and transcribed, focused on use of GRADE including the reasoning underlying, and factors contributing to, discordant recommendations., Results: Four themes emerged: strengths of GRADE, challenges and barriers to GRADE, strategies to improve GRADE application, and explanations for discordant recommendations. Reasons for discordant recommendations included skepticism about the value of making conditional recommendations; political considerations; high certainty in benefits (sometimes warranted, sometimes not) despite assessing evidence as low certainty; and concerns that conditional recommendations will be ignored., Conclusion: WHO panelists make discordant recommendations inconsistent with GRADE guidance for reasons that include limitations in their understanding of GRADE. Ensuring optimal application of GRADE at WHO and elsewhere likely requires selecting panelists who have a commitment to GRADE principles, additional training of panelists, and formal processes to maximize adherence to GRADE principles., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.

Poor control of cardiovascular disease accounts for a substantial proportion of the disease burden in developing countries, but often essential anticoagulant medicines for preventing strokes and embolisms are not widely available. In 2019, direct oral anticoagulants were added to the World Health Organization's WHO Model list of essential medicines. The aims of this paper are to summarize the benefits of direct oral anticoagulants for patients with cardiovascular disease and to discuss ways of increasing their usage internationally. Although the cost of direct oral anticoagulants has provoked debate, the affordability of introducing these drugs into clinical practice could be increased by: price negotiation; pooled procurement; competitive tendering; the use of patent pools; and expanded use of generics. In 2017, only 14 of 137 countries that had adopted national essential medicines lists included a direct oral anticoagulant on their lists. This number could increase rapidly if problems with availability and affordability can be tackled. Once the types of patient likely to benefit from direct oral anticoagulants have been clearly defined in clinical practice guidelines, coverage can be more accurately determined and associated costs can be better managed. Government action is required to ensure that direct oral anticoagulants are covered by national budgets because the absence of reimbursement remains an impediment to achieving universal coverage. Tackling cardiovascular disease with the aid of direct oral anticoagulants is an essential component of efforts to achieve the World Health Organization's target of reducing premature deaths due to noncommunicable disease by 25% by 2025. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19).Purpose: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19.Data Sources: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020.Study Selection: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included.Data Extraction: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews).Data Synthesis: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs.Limitation: Direct studies in COVID-19 are limited and poorly reported.Conclusion: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers.Primary Funding Source: World Health Organization. (PROSPERO: CRD42020178187). [ABSTRACT FROM AUTHOR]

Systematic reviews are essential to produce trustworthy guidelines. To assess the certainty of a body of evidence included in a systematic review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group has developed an approach that is currently used by over 100 organizations, including the World Health Organization and the Cochrane Collaboration. GRADE provides operational definitions and instructions to rate the certainty of the evidence for each outcome in a review as high, moderate, low, or very low for the effects of interventions, prognostic estimates, values and preferences, test accuracy, and resource utilization. The assessment includes assessing risk of bias, imprecision, inconsistency, indirectness, and publication bias, the magnitude of effects, dose‐response relations, and the impact of residual confounding and bias. Summary statistical information and assessments of certainty are presented in GRADE evidence summary tables, which can be produced using GRADE's official GRADEpro software tool (www.gradepro.org/). The evidence summary tables feed into the GRADE Evidence to Decision frameworks which guideline panels can use to produce recommendations. [ABSTRACT FROM AUTHOR]

Background and Aims The World Health Organization ( WHO), and a growing number of other organizations, have adopted the Grading of Recommendations, Assessment, Development and Evaluation ( GRADE) system in order to both assess the quality of research evidence and develop clinical practice guidelines. In 2009 WHO published a guideline on psychosocially assisted pharmacological treatment of opioid dependence, based on the results of Cochrane Reviews summarized using the GRADE methodology. The main features of this system are an a priori definition of outcomes and their relevance, and distinction between the quality of evidence (also referred to as confidence in the estimate of intervention effect) and the strength of recommendations. We consider how successful this approach has been. Analysis and Evidence We discuss the merits and limitations of using Cochrane Reviews and GRADE framework in developing guidelines in the field of drug addiction. In 2009 a panel of multi-disciplinary international experts identified 15 clinical questions and eight relevant outcomes. Cochrane reviews were available for each clinical question and four outcomes. The panel formulated 15 recommendations. Eight recommendations were classified as strong, two of which were based on high-quality evidence and three on very low-quality evidence. For example, the strong recommendation to use methadone in adequate doses in preference to buprenorphine was based on high-quality evidence, while the strong recommendation not to use the combination of opioid antagonists with heavy sedation in the management of opioid withdrawal was based on low-quality evidence. Conclusions An explicit stepwise process of moving from evaluation of the quality of evidence to the definition of the strength of recommendations is important in providing practical and clear clinical guidance for practitioners and policy-makers in addiction. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) Department of HIV/AIDS led the development of public health guidelines for delivering an evidence-based, essential package of interventions for the prevention and treatment of HIV and other sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender people in the health sector in low- and middle-income countries. The objective of this paper is to review the methodological challenges faced and solutions applied during the development of the guidelines. Methods: The development of the guidelines followed the WHO guideline development process, which utilizes the GRADE approach. We identified, categorized and labeled the challenges identified in the guidelines development process and described the solutions through an interactive process of in-person and electronic communication. Results: We describe how we dealt with the following challenges: (1) heterogeneous and complex interventions; (2) paucity of trial data; (3) selecting outcomes of interest; (4) using indirect evidence; (5) integrating values and preferences; (6) considering resource use; (7) addressing social and legal barriers; (8) wording of recommendations; and (9) developing global guidelines. Conclusion: We were able to successfully apply the GRADE approach for developing recommendations for public health interventions. Applying the general principles of the approach while carefully considering specific challenges can enhance both the process and the outcome of guideline development. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the sixth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on determining which outcomes are important for the development of guidelines. Methods: We searched five databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct a complete systematic review ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: We did not find a systematic review that addresses any of the following key questions and we found limited relevant research evidence. What methods should WHO use to identify important outcomes? • Methods of outcome identification should be transparent and explicit. • The consultation process should start with identification of all relevant outcomes associated with an intervention. • Those affected, including consumers, should be involved in the selection of outcomes. • A question driven approach (what is important?) is preferable to a data driven approach (what data are at hand?) to identify important outcomes. What type of outcomes should WHO consider and how should cultural diversity be taken account of in the selection of outcomes? • Desirable (benefits, less burden and savings) and undesirable effects should be considered in all guidelines. • Undesirable effects include harms (including the possibility of unanticipated adverse effects), greater burden (e.g. having to go to the doctor) and costs (including opportunity costs). • Important outcomes (e.g. mortality, morbidity, quality of life) should be preferred over surrogate, indirect outcomes (e.g. cholesterol levels, lung function) that may or may not correlate with patient important outcomes. • Ethical considerations should be part of the evaluation of important outcomes (e.g. impacts on autonomy). • If the importance of outcomes is likely to vary across cultures, stakeholders from diverse cultures should be consulted and involved in the selection of outcomes. How should the importance of outcomes be ranked? • Outcomes should be ranked by relative importance, separated into benefits and downsides. • Information from research on values and preferences should inform the ranking of outcomes whenever possible. • If the importance of outcomes is likely to vary across cultures, ranking of outcomes should be done in specific settings. • If evidence is lacking for an important outcome, this should be acknowledged, rather than ignoring the outcome. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 10th of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on integrating values and consumers in guideline development. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We did not conduct a full systematic review ourselves. Our conclusions based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: We did not find a systematic review of methods for integrating values in guidelines, but we found several systematic reviews that dealt with related topics. Whose values should WHO use when making recommendations? • Values, the relative importance or worth of a state or consequences of a decision (outcomes relating to benefits, harms, burden and costs), play a role in every recommendation. Ethical considerations, concepts that determine what is right, also play a role. • The values used in making recommendations should reflect those of the people affected. Judgements should be explicit and should be informed by input from those affected (including citizens, patients, clinicians and policy makers). • When differences in values may lead to different decisions or there is uncertainty about values, this should also be explicit. If differences in values are likely to affect a decision, such that people in different setting would likely make different choices about interventions or actions based on differences in their values, global recommendations should be explicit in terms of which values were applied and allow for adaptation after incorporating local values. How should WHO ensure that appropriate values are integrated in recommendations? • All WHO guideline groups should uniformly apply explicit, transparent and clearly described methods for integrating values. • WHO should consider involving relevant stakeholders if this is feasible and efficient. • WHO should develop a checklist for guidelines panels to help them to ensure that ethical considerations relevant to recommendations are addressed explicitly and transparently. How should users and consumers be involved in generating recommendations? • Including consumers in groups that are making global recommendations presents major challenges with respect to the impossibility of including a representative spectrum of consumers from a variety of cultures and settings. Nonetheless, consideration should be given to including consumers in groups who are able to challenge assumptions that are made about the values used for making recommendations, rather than represent the values of consumers around the world. • WHO should establish a network to facilitate involvement of users. • Draft recommendations should be reviewed by consumers, who should be asked explicitly to consider the values that were used.… [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the fifth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objective: In this review we address approaches to facilitate sound processes within groups that develop recommendations for health care. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key question and answer: What should WHO do to ensure appropriate group processes? Various strategies can be adopted to ensure that the group processes in play when panels are developing recommendations are inclusive, so that all voices can be heard and all arguments given fair weight, including • the use of formal consensus development methods, such at the Nominal Group Technique or the Delphi method • the selection of a group leader who is qualified and responsible for facilitating an appropriate group process. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the last of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on evaluating guidelines and recommendations, including their quality, whether they are likely to be up-to-date, and their implementation. We also considered the role of guideline developers in undertaking evaluations that are needed to inform recommendations. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: Our answers to these questions were informed by a review of instruments for evaluating guidelines, several studies of the need for updating guidelines, discussions of the pros and cons of different research designs for evaluating the implementation of guidelines, and consideration of the use of uncertainties identified in systematic reviews to set research priorities. How should the quality of guidelines or recommendations be appraised? • WHO should put into place processes to ensure that both internal and external review of guidelines is undertaken routinely. • A checklist, such as the AGREE instrument, should be used. • The checklist should be adapted and tested to ensure that it is suitable to the broad range of recommendations that WHO produces, including public health and health policy recommendations, and that it includes questions about equity and other items that are particularly important for WHO guidelines. When should guidelines or recommendations be updated? • Processes should be put into place to ensure that guidelines are monitored routinely to determine if they are in need of updating. • People who are familiar with the topic, such as Cochrane review groups, should do focused, routine searches for new research that would require revision of the guideline. • Periodic review of guidelines by experts not involved in developing the guidelines should also be considered. • Consideration should be given to establishing guideline panels that are ongoing, to facilitate routine updating, with members serving fixed periods with a rotating membership. How should the impact of guidelines or recommendations be evaluated? • WHO headquarters and regional offices should support member states and those responsible for policy decisions and implementation to evaluate the impact of their decisions and actions by providing advice regarding impact assessment, practical support and coordination of efforts. • Before-after evaluations should be used cautiously and when there are important uncertainties regarding the effects of a policy or its implementation, randomised evaluations should be used when possible. What responsibility should WHO take for ensuring that important uncertainties are addressed by future research when the evidence needed to inform recommendations is lacking? • Guideline panels should routinely identify important uncertainties and research priorities. This source of potential priorities for research should be used systematically to inform priority-setting processes for global research. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 15th of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: In this review we address strategies for the implementation of recommendations in health care. Methods: We examined overviews of systematic reviews of interventions to improve health care delivery and health care systems prepared by the Cochrane Effective Practice and Organisation of Care (EPOC) group. We also conducted searches using PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: What should WHO do to disseminate and facilitate the uptake of recommendations? • WHO should choose strategies to implement their guidelines from among those which have been evaluated positively in the published literature on implementation research • Because the evidence base is weak and modest to moderate effects, at best, can be anticipated, WHO should promote rigorous evaluations of implementation strategies. What should be done at headquarters, by regional offices and in countries? • Adaptation and implementation of WHO guidelines should be done locally, at the national or sub-national level. • WHO headquarters and regional offices should support the development and evaluation of implementation strategies by local authorities. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 14th of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on reporting guidelines and recommendations. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: There is little empirical evidence that addresses these questions. Our answers are based on logical arguments and standards put forward by other groups. What standard types of recommendations or reports should WHO use? • WHO should develop standard formats for reporting recommendations to facilitate recognition and use by decision makers for whom the recommendations are intended, and to ensure that all the information needed to judge the quality of a guideline, determine its applicability and, if needed, adapt it, is reported. • WHO should develop standard formats for full systematically developed guidelines that are sponsored by WHO, rapid assessments, and guidelines that are endorsed by WHO. • All three formats should include the same information as full guidelines, indicating explicitly what the group preparing the guideline did not do, as well as the methods that were used. • These formats should be used across clinical, public health and health systems recommendations. How should recommendations be formulated and reported? • Reports should be structured, using headings that correspond to those suggested by the Conference on Guideline Standardization or similar headings. • The quality of evidence and strength of recommendations should be reported explicitly using a standard approach. • The way in which recommendations are formulated should be adapted to the specific characteristics of a specific guideline. • Urgent attention should be given to developing a template that provides decision makers with the relevant global evidence that is needed to inform a decision and offers practical methods for incorporating the context specific evidence and judgements that are needed. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 12th of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on incorporating considerations of equity in guidelines and recommendations. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: We found few directly relevant empirical methodological studies. These answers are based largely on logical arguments. When and how should inequities be addressed in systematic reviews that are used as background documents for recommendations? • The following question should routinely be considered: Are there plausible reasons for anticipating differential relative effects across disadvantaged and advantaged populations? • If there are plausible reasons for anticipating differential effects, additional evidence should be included in a review to inform judgments about the likelihood of differential effects. What questions about equity should routinely be addressed by those making recommendations on behalf of WHO? • The following additional questions should routinely be considered: • How likely is it that the results of available research are applicable to disadvantaged populations and settings? • How likely are differences in baseline risk that would result in differential absolute effects across disadvantaged and advantaged populations? • How likely is it that there are important differences in trade-offs between the expected benefits and harms across disadvantaged and advantaged populations? • Are there different implications for disadvantaged and advantaged populations, or implications for addressing inequities? What context specific information is needed to inform adaptation and decision making in a specific setting with regard to impacts on equity? • Those making recommendations on behalf of WHO should routinely consider and offer advice about the importance of the following types of context specific data that might be needed to inform adaptation and decision making in a specific setting: • Effect modifiers for disadvantaged populations and for the likelihood of differential effects • Baseline risk in relationship to social and economic status • Utilization and access to care in relationship to social and economic status • Costs in relationship to social and economic status • Ethics and laws that may impact on strategies for addressing inequities • Availability of resources to address inequities What implementation strategies are likely be needed to ensure that recommendations are implemented equitably? • Organisational changes are likely to be important to address inequities. While it may only be possible to consider these in relationship to specific settings, consideration should be given to how best to provide support for identifying and addressing needs for organisational changes. In countries with pervasive inequities institutional, cultural and political changes may first be needed. • Appropriate indicators of social and economic status should be used to monitor the effects of implementing recommendations on disadvantaged populations and on changes in social and economic status. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the thirteenth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on applicability, transferability, and adaptation of guidelines. Methods: We searched five databases for existing systematic reviews and relevant primary methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We used the definition "coming from, concerning or belonging to at least two or all nations" for the term international. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: We did not identify systematic reviews addressing the key questions. We found individual studies and projects published in the peer reviewed literature and on the Internet. Should WHO develop international recommendations? • Resources for developing high quality recommendations are limited. Internationally developed recommendations can facilitate access to and pooling of resources, reduce unnecessary duplication, and involve international scientists. • Priority should be given to international health problems and problems that are important in low and middle-income countries, where these advantages are likely to be greatest. • Factors that influence the transferability of recommendations across different settings should be considered systematically and flagged, including modifying factors, important variation in needs, values, costs and the availability of resources. What should be done centrally and locally? • The preparation of systematic reviews and evidence profiles should be coordinated centrally, in collaboration with organizations that produce systematic reviews. Centrally developed evidence profiles should be adaptable to specific local circumstances. • Consideration should be given to models that involve central coordination with work being undertaken by centres located throughout the world. • While needs, availability of resources, costs, the presence of modifying factors and values need to be assessed locally, support for undertaking these assessments may be needed to make guidelines applicable. • WHO should provide local support for adapting and implementing recommendations by developing tools, building capacity, learning from international experience, and through international networks that support evidence-informed health policies, such as the Evidence-informed Policy Network (EVIPNet). How should recommendations be adapted? • WHO should provide detailed guidance for adaptation of international recommendations. • Local adaptation processes should be systematic and transparent, they should involve stakeholders, and they should report the key factors that influence decisions, including those flagged in international guidelines, and the reasons for any modifications that are made. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the seventh of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on what constitutes "evidence" in guidelines and recommendations. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key question and answers: We found several systematic reviews that compared the findings of observational studies with randomised trials, a systematic review of methods for evaluating bias in non-randomised trials and several descriptive studies of methods used in systematic reviews of population interventions and harmful effects. What types of evidence should be used to address different types of questions? • The most important type of evidence for informing global recommendations is evidence of the effects of the options (interventions or actions) that are considered in a recommendation. This evidence is essential, but not sufficient for making recommendations about what to do. Other types of required evidence are largely context specific. • The study designs to be included in a review should be dictated by the interventions and outcomes being considered. A decision about how broad a range of study designs to consider should be made in relationship to the characteristics of the interventions being considered, what evidence is available, and the time and resources available. • There is uncertainty regarding what study designs to include for some specific types of questions, particularly for questions regarding population interventions, harmful effects and interventions where there is only limited human evidence. • Decisions about the range of study designs to include should be made explicitly. • Great caution should be taken to avoid confusing a lack of evidence with evidence of no effect, and to acknowledge uncertainty. • Expert opinion is not a type of study design and should not be used as evidence. The evidence (experience or observations) that is the basis of expert opinions should be identified and appraised in a systematic and transparent way. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the ninth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on grading evidence and recommendations in guidelines. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct a full systematic review ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: Should WHO grade the quality of evidence and the strength of recommendations? • Users of recommendations need to know how much confidence they can place in the underlying evidence and the recommendations. The degree of confidence depends on a number of factors and requires complex judgments. These judgments should be made explicitly in WHO recommendations. A systematic and explicit approach to making judgments about the quality of evidence and the strength of recommendations can help to prevent errors, facilitate critical appraisal of these judgments, and can help to improve communication of this information. What criteria should be used to grade evidence and recommendations? • Both the quality of evidence and the strength of recommendations should be graded. The criteria used to grade the strength of recommendations should include the quality of the underlying evidence, but should not be limited to that. • The approach to grading should be one that has wide international support and is suitable for a wide range of different types of recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which is currently suggested in the Guidelines for WHO Guidelines, is being used by an increasing number of other organizations internationally. It should be used more consistently by WHO. Further developments of this approach should ensure its wide applicability. Should WHO use the same grading system for all of its recommendations? • Although there are arguments for and against using the same grading system across a wide range of different types of recommendations, WHO should use a uniform grading system to prevent confusion for developers and users of recommendations. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the eighth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on the synthesis and presentation of research evidence, focusing on four key questions. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: We found two reviews of instruments for critically appraising systematic reviews, several studies of the importance of using extensive searches for reviews and determining when it is important to update reviews, and consensus statements about the reporting of reviews that informed our answers to the following questions. How should existing systematic reviews be critically appraised? • Because preparing systematic reviews can take over a year and require capacity and resources, existing reviews should be used when possible and updated, if needed. • Standard criteria, such as A MeaSurement Tool to Assess Reviews (AMSTAR), should be used to critically appraise existing systematic reviews, together with an assessment of the relevance of the review to the questions being asked. When and how should WHO undertake or commission new reviews? • Consideration should be given to undertaking or commissioning a new review whenever a relevant, up-to-date review of good quality is not available. • When time or resources are limited it may be necessary to undertake rapid assessments. The methods that are used to do these assessments should be reported, including important limitations and uncertainties and explicit consideration of the need and urgency of undertaking a full systematic review. • Because WHO has limited capacity for undertaking systematic reviews, reviews will often need to be commissioned when a new review is needed. Consideration should be given to establishing collaborating centres to undertake or support this work, similar to what some national organisations have done. How should the findings of systematic reviews be summarised and presented to committees responsible for making recommendations? • Concise summaries (evidence tables) of the best available evidence for each important outcome, including benefits, harms and costs, should be presented to the groups responsible for making recommendations. These should include an assessment of the quality of the evidence and a summary of the findings for each outcome. • The full systematic reviews, on which the summaries are based, should also be available to both those making recommendations and users of the recommendations. What additional information is needed to inform recommendations and how should this information be synthesised with information about effects and presented to committees? • Additional information that is needed to inform recommendations includes factors that might modify the expected effects, need (prevalence, baseline risk or status), values (the relative importance of key outcomes), costs and the availability of resources. • Any assumptions that are made about values or other factors that may vary from setting to setting should be made explicit.… [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the third of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objective: In this review we address the composition of guideline development groups and consultation processes during guideline development. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: What should be the composition of a WHO-panel that is set up to develop recommendations? The existing empirical evidence suggests that panel composition has an impact on the content of the recommendations that are made. There is limited research evidence to guide the exact composition of a panel. Based on logical arguments and the experience of other organisations we recommend the following: • Groups that develop guidelines or recommendations should be broadly composed and include important stakeholders such as consumers, health professionals that work within the relevant area, and managers or policy makers. • Groups should include or have access to individuals with the necessary technical skills, including information retrieval, systematic reviewing, health economics, group facilitation, project management, writing and editing. • Groups should include or have access to content experts. • To work well a group needs an effective leader, capable of guiding the group in terms of the task and process, and capable of facilitating collaboration and balanced contribution from all of the group members. • Because many group members will not be familiar with the methods and processes that are used in developing recommendations, groups should be offered training and support to help ensure understanding and facilitate active participation. What groups should be consulted when a panel is being set up? We did not identify methodological research that addressed this question, but based on logical arguments and the experience of other organisations we recommend that as many relevant stakeholder groups as practical should be consulted to identify suitable candidates with an appropriate mix of perspectives, technical skills and expertise, as well as to obtain a balanced representation with respect to regions and gender. What methods should WHO use to ensure appropriate consultations? We did not find any references that addressed issues related to this question. Based on logical arguments and the experience of other organisations we believe that consultations may be desirable at several stages in the process of developing guidelines or recommendations, including: • Identifying and setting priorities for guidelines and recommendations • Commenting on the scope of the guidelines or recommendations • Commenting on the evidence that is used to inform guidelines or recommendations • Commenting on drafts of the guidelines or recommendations • Commenting on plans for disseminating and supporting the adaptation and implementation of the guidelines or recommendations. • Key stakeholder organisations should be contacted directly whenever possible. • Consultation processes should be transparent and should encourage feedback from interested parties. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the second of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on priority setting for health care guidelines, recommendations and technology assessments. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: There is little empirical evidence to guide the choice of criteria and processes for establishing priorities, but there are broad similarities in the criteria that are used by various organisations and practical arguments for setting priorities explicitly rather than implicitly, What criteria should be used to establish priorities?: • WHO has limited resources and capacity to develop recommendations. It should use these resources where it has the greatest chance of improving health, equity, and efficient use of healthcare resources. • We suggest the following criteria for establishing priorities for developing recommendations based on WHO's aims and strategic advantages: • Problems associated with a high burden of illness in low and middle-income countries, or new and emerging diseases. • No existing recommendations of good quality. • The feasibility of developing recommendations that will improve health outcomes, reduce inequities or reduce unnecessary costs if they are implemented. • Implementation is feasible, will not exhaustively use available resources, and barriers to change are not likely to be so high that they cannot be overcome. • Additional priorities for WHO include interventions that will likely require system changes and interventions where there might be a conflict in choices between individual and societal perspectives. What processes should be used to agree on priorities?: • The allocation of resources to the development of recommendations should be part of the routine budgeting process rather than a separate exercise. • Criteria for establishing priorities should be applied using a systematic and transparent process. • Because data to inform judgements are often lacking, unmeasured factors should also be considered - explicitly and transparently. • The process should include consultation with potential end users and other stakeholders, including the public, using well-constructed questions, and possibly using Delphi-like procedures. • Groups that include stakeholders and people with relevant types of expertise should make decisions. Group processes should ensure full participation by all members of the group. • The process used to select topics should be documented and open to inspection. Should WHO have a centralised or decentralised process?: • Both centralised and decentralised processes should be used. Decentralised processes can be considered as separate "tracks". • Separate tracks should be used for considering issues for specific areas, populations, conditions or concerns. The rationales for designating special tracks should be defined clearly; i.e. why they warrant special consideration. • Updating of guidelines could also be considered as a separate "track", taking account of issues such as the need for corrections and the availability of new evidence. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the first of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. Objectives: We reviewed the literature on guidelines for the development of guidelines. Methods: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. Key questions and answers: We found no experimental research that compared different formats of guidelines for guidelines or studies that compared different components of guidelines for guidelines. However, there are many examples, surveys and other observational studies that compared the impact of different guideline development documents on guideline quality. What have other organizations done to develop guidelines for guidelines from which WHO can learn?: • Establish a credible, independent committee that evaluates existing methods for developing guidelines or that updates existing ones. • Obtain feedback and approval from various stakeholders during the development process of guidelines for guidelines. • Develop a detailed source document (manual) that guideline developers can use as reference material. What should be the key components of WHO guidelines for guidelines?: • Guidelines for guidelines should include information and instructions about the following components: 1) Priority setting; 2) Group composition and consultations; 3) Declaration and avoidance of conflicts of interest; 4) Group processes; 5) Identification of important outcomes; 6) Explicit definition of the questions and eligibility criteria ; 7) Type of study designs for different questions; 8) Identification of evidence; 9) Synthesis and presentation of evidence; 10) Specification and integration of values; 11) Making judgments about desirable and undesirable effects; 12) Taking account of equity; 13) Grading evidence and recommendations; 14) Taking account of costs; 15) Adaptation, applicability, transferability of guidelines; 16) Structure of reports; 17) Methods of peer review; 18) Planned methods of dissemination & implementation; 19) Evaluation of the guidelines. What have other organizations done to implement guidelines for guidelines from which WHO can learn?: • Obtain buy-in from regions and country level representatives for guidelines for guidelines before dissemination of a revised version. • Disseminate the guidelines for guidelines widely and make them available (e.g. on the Internet). • Develop examples of guidelines that guideline developers can use as models when applying the guidelines for guidelines. • Ensure training sessions for those responsible for developing guidelines. • Continue to monitor the methodological literature on guideline development. [ABSTRACT FROM AUTHOR]

In 2005 the World Health Organisation (WHO) asked its Advisory Committee on Health Research (ACHR) for advice on ways in which WHO can improve the use of research evidence in the development of recommendations, including guidelines and policies. The ACHR established the Subcommittee on the Use of Research Evidence (SURE) to collect background documentation and consult widely among WHO staff, international experts and end users of WHO recommendations to inform its advice to WHO. We have prepared a series of reviews of methods that are used in the development of guidelines as part of this background documentation. We describe here the background and methods of these reviews, which are being published in Health Research Policy and Systems together with this introduction. [ABSTRACT FROM AUTHOR]

Background: Situations such as public health emergencies and outbreaks necessitate the development and publication of high-quality recommendations within a condensed timeframe. For example, WHO has produced examples of and guidance for the development of rapid guidelines (RGs). However, more information is needed to understand the experiences and perceptions of guideline developers. This is the second of a series of three articles addressing methodological issues around RGs. This study describes the perceptions and experiences of guideline developers at WHO about RGs.Methods: We conducted interviews consisting of open- and closed-ended questions with guideline developers at WHO. Our analysis described the definition and rationale of RGs, the differences from regular guidelines with regard to timelines from topic definition until publication, barriers to identifying the evidence and the lack of a standard methodology to develop RGs.Results: We interviewed 10 participants, the majority of whom were comfortable with the current WHO definition of RGs. Most stated that the rationale for developing RGs should be in response to new evidence about efficacy, cost-effectiveness or safety. Respondents differed with regards to the amount of time RGs should take. While the majority of participants agreed that guidelines should be based on a systematic review, this step in the process was considered the most time and resource intensive. Challenges for developing RGs included limited personnel and financial resources as well as the lack of evidence. Facilitators, in turn, that may improve RG development include additional financial and personnel resources as well as the use of virtual meetings.Conclusions: While our study suggests a strong need and rationale for the development of RGs, standardisation of timelines and guidance on panel composition, peer-review process, conduct of meetings and sources of permissible evidence require further research. [ABSTRACT FROM AUTHOR]

Background: Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated.Objectives: To conduct systematic reviews of randomized and nonrandomized studies for effects of cryotherapy, loop electrosurgical excision procedure (LEEP), and cold knife conization (CKC) as treatment for CIN 2-3.Search Strategy: Medline, Embase, and other databases were searched to February 2012 for benefits, and to July 2012 for harms. Additionally, experts were contacted. Keywords for CIN, cervical cancer, and the treatments were used.Selection Criteria: Studies of nonpregnant women 18 years or older not previously treated for CIN were included.Data Collection and Analysis: Two investigators independently screened and collected data. Relative risks and proportions were calculated and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation).Main Results: Recurrence rate was 5.3% 12 months after cryotherapy or LEEP, and 1.4% after CKC. There seemed to be little or no differences in frequency of complications after LEEP or cryotherapy, but they occurred more often after CKC. Evidence suggests premature delivery is most common with CKC, but it also occurs after LEEP and cryotherapy.Conclusions: Despite a comprehensive search, there is very low quality evidence and often no evidence for important outcomes, including reproductive outcomes and complications. Studies assessing these outcomes are needed. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings.Methods: We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047.Findings: Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] -10·2%, 95% CI -11·5 to -7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; pinteraction=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD -14·3%, -15·9 to -10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12-16-layer cotton masks; pinteraction=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD -10·6%, 95% CI -12·5 to -7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings.Interpretation: The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance.Funding: World Health Organization. [ABSTRACT FROM AUTHOR]

Background: Aspirin desensitization is increasingly recommended for the treatment of aspirin‐exacerbated respiratory disease (AERD). The objective of this study is to systematically review the efficacy and safety of aspirin desensitization in patients with AERD. Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception to January 5, 2019. We included randomized trials and comparative observational studies in any language. Data extraction and risk of bias assessment were performed in duplicate independently. Results: Five randomized controlled trials (RCTs) enrolled 233 patients with AERD. Compared to placebo, aspirin desensitization (mean daily dose 800 mg) improved quality of life (risk ratio [RR] 2.00; 95% confidence interval [CI], 1.31 to 3.06; heterogeneity measure [I2] = 0%; risk difference [RD] +24%; 22‐item Sino‐Nasal Outcome Test [SNOT‐22] scale [0 to 110, higher worse]; mean difference [MD] −10.27 [95% CI, −6.39 to −14.15]; moderate‐certainty); and respiratory symptoms (RR 2.20 [95% CI, 1.55 to 2.73], I2 = 34%, RD +36%; American Academy of Otolaryngology (AAO) scale [0 to 20, higher worse]; MD −2.56 [95% CI,−1.12 to −3.92]; high‐certainty). Aspirin desensitization increased adverse events severe enough to cause treatment discontinuation (major bleeding, gastritis, asthma exacerbation, or rash causing drug discontinuation, RR 4.39 [95% CI, 1.43 to 13.50], I2 = 0%, RD +11%, moderate‐certainty), and gastritis (RR 3.84 [95% CI, 1.12 to 13.19], I2 = 0%, RD +9%, low‐certainty). Findings were robust to sensitivity analyses. Two available observational studies were not informative because they lacked adjustment for confounders and/or contemporaneous controls. Conclusion: In patients with AERD, moderate‐certainty and high‐certainty evidence shows that aspirin desensitization meaningfully reduces symptoms of rhinosinusitis and improves quality of life, but results in a significant increase in adverse events. [ABSTRACT FROM AUTHOR]