Addressing Multimorbidity in Evidence Integration and Synthesis

To minimize bias, clinical practice guidelines (CPG) for managing patients with multiple conditions should be informed by well-planned syntheses of the totality of the relevant evidence by means of systematic reviews and meta-analyses. However, deficiencies along the entire evidentiary pathway hinder the development of evidence-based CPGs. Published reports of trials and observational studies often do not provide usable data on treatment effect heterogeneity, perhaps because their design, analysis and presentation is seldom geared towards informing on how multimorbidity modifies the effect of treatments. Systematic reviews and meta-analyses inherit all the limitations of their building blocks and introduce additional of their own, including selection biases at the level of the included studies, ecological biases, and analytical challenges. To generate recommendations to help negotiate some of the challenges in synthesizing the primary literature, so that the results of the evidence synthesis is applicable to the care of those with multiple conditions. Informal group process. We have built upon established general guidance, and provide additional recommendations specific to systematic reviews that could improve the CPGs for multimorbid patients. We suggest that following the additional recommendations is good practice, but acknowledge that not all proposed recommendations are of equal importance, validity and feasibility, and that further work is needed to test and refine the recommendations.     

Guidelines International Network: toward international standards for clinical practice guidelines

Guideline development processes vary substantially, and many guidelines do not meet basic quality criteria. Standards for guideline development can help organizations ensure that recommendations are evidence-based and can help users identify high-quality guidelines. Such organizations as the U.S. Institute of Medicine and the United Kingdom's National Institute for Health and Clinical Excellence have developed recommendations to define trustworthy guidelines within their locales. Many groups charged with guideline development find the lengthy list of standards developed by such organizations to be aspirational but infeasible to follow in entirety. Founded in 2002, the Guidelines International Network (G-I-N) is a network of guideline developers that includes 93 organizations and 89 individual members representing 46 countries. The G-I-N board of trustees recognized the importance of guideline development processes that are both rigorous and feasible even for modestly funded groups to implement and initiated an effort toward consensus about minimum standards for high-quality guidelines. In contrast to other existing standards for guideline development at national or local levels, the key components proposed by G-I-N will represent the consensus of an international, multidisciplinary group of active guideline developers. This article presents G-I-N's proposed set of key components for guideline development. These key components address panel composition, decision-making process, conflicts of interest, guideline objective, development methods, evidence review, basis of recommendations, ratings of evidence and recommendations, guideline review, updating processes, and funding. It is hoped that this article promotes discussion and eventual agreement on a set of international standards for guideline development.     

AGREEing on Canadian cardiovascular clinical practice guidelines

The use of clinical practice guidelines (CPGs), particularly the routine implementation of evidence-based cardiovascular health maintenance and disease management recommendations, affords both expert and nonexpert practitioners the opportunity to achieve better, and at least theoretically similar, patient outcomes. However, health care practitioners are often stymied in their efforts to follow even well-researched and well-written CPGs as a consequence of contradictory information. The purposeful integration and harmonization of Canadian cardiovascular CPGs, regardless of their specific risk factor or clinical management focus, is critical to their widespread acceptance and implementation. This level of cooperation and coordination among CPG groups and organizations would help to ensure that their clinical practice roadmaps (ie, best practice recommendations) contain clear, concise and complementary, rather than contradictory, patient care information. Similarly, the application of specific tools intended to improve the quality of CPGs, such as the Appraisal of Guidelines for Research and Evaluation (AGREE) assessment tool, may also lead to improvements in CPG quality and potentially enhance their acceptance and implementation.     

Incorporating the patient perspective: a critical review of clinical practice guidelines for implantable cardioverter defibrillator therapy

Purpose

Implantable cardioverter defibrillators (ICDs) are recommended for patients with heart failure and/or ventricular arrhythmias at risk of sudden cardiac death. Guidelines for ICD implantation are derived from robust clinical data. However, critical factors which might influence treatment decisions include patient preferences. We set out to determine how clinical practice guidelines (CPGs) incorporate the patient perspective into supporting decision making about ICDs.

Methods

CPGs on ICD implantation were purposively selected from national and professional bodies in Europe, North America and Australasia. CPGs were then appraised according to three key domains of shared decision making: (a) informing patients about the risks, benefits and consequences known to be important to patients; (b) personalising risks and benefits and (c) involvement of patient (plus family/significant others if desired) in decision making.

Results

Appraisal of six current CPGs found major deficiencies or inconsistencies in guidance. CPGs tended to focus on evidence of device effectiveness, with sparse consideration of other outcomes important to patients such as impacts on quality of life and psychosocial well-being. Little reference was made to involvement of the patient in decision making.

Conclusions

This suggests that embedding shared decision in CPGs will improve the patient-centeredness of ICD treatment by enabling patients to make informed, value-based decisions. Specific recommendations for CPG development include the need for signposting to preference sensitive decision points as well as inclusion of a broader range of outcomes which are known to be important to patients when deciding whether or not to have a device fitted.     

Inclusion of Performance Parameters and Patient Context in the Clinical Practice Guidelines for Heart Failure

BackgroundTo facilitate evidence-based medicine (EBM) on an individual level, it may be important for clinical practice guidelines (CPGs) to incorporate the performance parameters of diagnostic studies and therapeutic interventions (such as likelihood ratio and absolute benefit or harm), and to incorporate relevant patient contexts that may influence decision-making. We sought to determine the extent to which heart failure CPGs currently incorporate this information.MethodsWe reviewed the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 Heart Failure CPG, the 2017 ACCF/AHA/HFSA update, and European Society of Cardiology (ESC) 2016 Heart Failure CPG. We abstracted variables for each CPG recommendation from the following domains: quality of evidence, strength of recommendation, diagnostic and therapeutic performance parameters, and patient context.ResultsWe examined 169 recommendations from the ACCF/AHA 2013 CPGs and 2017 update and 187 recommendations from the 2016 ESC CPGs. Performance parameters for diagnostic studies (2013 ACCF/AHA: 13%; 2017 ACCF/AHA/HFSA update: 0%; 2016 ESC: 0%) and therapeutic interventions (2013 ACCF/AHA: 65%; 2017 ACCF/AHA/HFSA update: 64%; 2016 ESC: 16%) were not commonly included in CPGs. Patient context was included in about half of ACCF/AHA recommendations and a quarter of ESC recommendations.ConclusionsThe majority of recommendations from heart failure CPGs lack information on diagnostic and therapeutic performance parameters and patient context. Given the importance of these components to effectively implement EBM, particularly for a heterogeneous heart failure population, innovative strategies are needed to optimize CPGs so they provide comprehensive yet succinct recommendations that can improve population-level outcomes and ensure optimal patient-centered care.     

Practice guidelines, a new reality in medicine. II. Methods of developing guidelines.

Current methods for developing practice guidelines include informal consensus development, formal consensus development, evidence-based guideline development, and explicit guideline development. Informal consensus development is the oldest and most common approach, but guidelines produced in this manner are often of poor quality and lack adequate documentation of methods. Formal consensus development uses a systematic approach to assess expert opinion and to reach agreement on recommendations. Evidence-based guideline development links recommendations directly to scientific evidence of effectiveness; rules of evidence are emphasized over expert opinion in making recommendations. Explicit guideline development clarifies the rationale by specifying the potential benefits, harms, and costs of available interventions; estimating the possibility of the outcomes; and comparing the desirability of the outcomes based on patient preferences. Steps in the development of practice guidelines include introductory decisions (selection of topic and panel members, clarification of purpose); assessments of clinical appropriateness (review of scientific evidence and expert opinion); assessment of public policy issues (resource limitations, feasibility issues); and guideline document development and evaluation (drafting of document, peer review, and pretesting).     

Canadian Thoracic Society: Presenting a new process for clinical practice guideline production

A key mandate of the Canadian Thoracic Society (CTS) is to promote evidence-based respiratory care through clinical practice guidelines (CPGs). To improve the quality and validity of the production, dissemination and implementation of its CPGs, the CTS has revised its guideline process and has created the Canadian Respiratory Guidelines Committee to oversee this process. The present document outlines the basic methodological tools and principles of the new CTS guideline production process. Important features include standard methods for choosing and formulating optimal questions and for finding, appraising, and summarizing the evidence; use of the Grading of Recommendations Assessment, Development and Evaluation system for rating the quality of evidence and strength of recommendations; use of the Appraisal of Guidelines for Research and Evaluation instrument for quality control during and after guideline development and for appraisal of other guidelines; use of the ADAPTE process for adaptation of existing guidelines to the local context; and use of the GuideLine Implementability Appraisal tool to augment implementability of guidelines. The CTS has also committed to develop guidelines in new areas, an annual guideline review cycle, and a new formal process for dissemination and implementation. Ultimately, it is anticipated that these changes will have a significant impact on the quality of care and clinical outcomes of individuals suffering from respiratory diseases across Canada.     

Levels of evidence in cardiovascular clinical practice guidelines

BACKGROUND: Clinical practice guidelines (CPGs) can be helpful in distilling the medical research literature for clinicians; however, the guidelines should acknowledge the variable methodological quality used in clinical research by tempering their recommendations with a 'levels of evidence' scale. OBJECTIVE: To evaluate the proportion of English-language cardiovascular CPGs that provide the user with recommendations graded according to a defined levels of evidence scale. In addition, to evaluate other key aspects important in the critical appraisal of CPGs. METHODS: CPGs for atrial fibrillation, congestive heart failure and myocardial infarction were identified by searching MEDLINE, a reference text of CPGs and the Internet. Each CPG was evaluated using a priori-defined criteria based on the Evidence-Based Medicine Working Group's paper on critical appraisal of CPGs, including use of a reproducible search strategy, method of obtaining consensus, peer review and testing in practice. RESULTS: A total of 95 CPGs were evaluated. Only 13% graded their recommendations using a defined levels of evidence scale. In addition, few CPGs documented a reproducible search strategy or peer review process, and none had been formally tested in practice. CONCLUSIONS: Reporting the levels of evidence for recommendations is an important component of CPGs, yet this system is not widely used.     

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease‐oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow‐up: strategies in care planning, self‐management and medication‐related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self‐management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.     

How should we set consumption thresholds for low risk drinking guidelines? Achieving objectivity and transparency using evidence,expert judgement and pragmatism

Most high‐income nations issue guidelines on low‐risk drinking to inform individuals’ decisions about alcohol consumption. However, leading scientists have criticized the processes for setting the consumption thresholds within these guidelines for a lack of objectivity and transparency. This paper examines how guideline developers should respond to such criticisms and focuses particularly on the balance between epidemiological evidence, expert judgement and pragmatic considerations. Although concerned primarily with alcohol, our discussion is also relevant to those developing guidelines for other health‐related behaviours. We make eight recommendations across three areas. First, recommendations on the use of epidemiological evidence: (1) guideline developers should assess whether the available epidemiological evidence is communicated most appropriately as population‐level messages (e.g. suggesting reduced drinking benefits populations rather than individuals); (2) research funders should prioritize commissioning studies on the acceptability of different alcohol‐related risks (e.g. mortality, morbidity, harms to others) to the public and other stakeholders; and (3) guideline developers should request and consider statistical analyses of epidemiological uncertainty. Secondly, recommendations to improve objectivity and transparency when translating epidemiological evidence into guidelines: (4) guideline developers should specify and publish their analytical framework to promote clear, consistent and coherent judgements; and (5) guideline developers’ decision‐making should be supported by numerical and visual techniques which also increase the transparency of judgements to stakeholders. Thirdly, recommendations relating to the diverse use of guidelines: (6) guideline developers and their commissioners should give meaningful attention to how guidelines are used in settings such as advocacy, health promotion, clinical practice and wider health debates, as well as in risk communication; (7) guideline developers should make evidence‐based judgements that balance epidemiological and pragmatic concerns to maximize the communicability, credibility and general effectiveness of guidelines; and (8) as with scientific judgements, pragmatic judgements should be reported transparently.     

The process of collecting and evaluating evidences for the development of Guidelines for the management of rheumatoid arthritis,Japan College of Rheumatology 2014: Utilization of GRADE approach

Objectives. To describe the process of collecting and evaluating evidence for treating rheumatoid arthritis (RA) for developing clinical practice guidelines (CPGs) for rheumatologists in Japan.

Methods. The task force comprised rheumatologists, epidemiologists, health economists, and patients. First, the critical outcomes were determined according to a three-round Delphi method, and eight topics with 88 clinical questions (CQs) were formulated. A systematic review of CQs was conducted using the Cochran Database of Systematic Reviews, MEDLINE, and Japana Centra Revvo Medicina (2003–2012). A questionnaire survey and focus group interview were performed to capture the patients’ values and preferences. Data from the National Health Insurance drug price list and product information provided by pharmaceutical companies were collected to evaluate drug cost and safety. The GRADE approach was used to describe the evidence quality and determine the strength of recommendations. Recommendations were developed using a modified Delphi method by a multidisciplinary panel including patients.

Results. Eight meetings and frequent e-mail communications were conducted to draft a quality assessment of evidence and recommendations. For 88 CQs, recommendation statements were determined.

Conclusions. Using the GRADE approach, new CPGs successfully addressed important clinical issues for treating RA patients. Timely updating of recommendations should be routinely considered.     

Evidence base in guideline generation in diabetes

During recent years much emphasis has been on the validity, reliability, reproducibility, clinical applicability, clarity, multidisciplinary process, scheduled review and documentation of clinical practice guidelines (CPGs). Still, CPGs show substantial variance in methodological quality. The present paper mainly focuses on two aspects that are particularly critical and contemporary from the perspective of evidence-based medicine: patient centredness and shared decision making, and conflict of interest. Sophisticated patient and consumer involvement at all stages of CPG development could be judged as being the gold standard. However, co-opting patients or consumer representatives and using other techniques of active patient involvement does not replace individual patient preferences in clinical decision-making processes. Current CPGs do not meet patient needs, since they do not provide concise, easy-to-read summaries of the benefits and risks of medicines together with more comprehensive scientific data as a prerequisite for informed or shared decision making. The vast majority of CPG panels have a financial conflict of interest (COI) and under-reporting is common. Not all organisations producing CPGs have set up COI policies, and existing policies vary widely. To solve the problem, CPG experts have recommended that methodologists without any important COI should lead the development process and have primary responsibility. There is a lot of room for other improvements through network transnational activities in the field of CPG development. Waste of time and resources should be avoided through sharing published and unpublished data identified, appraised and extracted for guideline development. The EASD could provide such a clearing house.     

Developing clinical practice guidelines in HIV rehabilitation: process recommendations and guiding principles

Our purpose was to develop process recommendations and guiding principles for future clinical practice guidelines in HIV rehabilitation. We conducted a scoping study that included focus group and interview consultations with 28 participants including people living with HIV, researchers, clinicians, educators, and policy stakeholders with expertise in HIV and rehabilitation. We used qualitative content analysis techniques to identify emergent themes related to the development of clinical practice guidelines. Results included seven recommendations for the process of developing clinical practice guidelines in HIV rehabilitation that spanned areas of flexibility, scope, adopting existing evidence from concurrent health conditions, format, interprofessional approach to development and implementation, terminology, and knowledge translation. Three guiding principles emerged to inform the philosophical approach for guideline development. These findings serve as a foundation for the development of clinical practice guidelines in HIV rehabilitation to enhance the care and treatment of people living with HIV.     

Guidelines for the management of pregnant women with obesity: A systematic review

Multiple clinical practice guidelines (CPGs) have been established for pregnant women with obesity. The quality and consistency of recommendations remain unknown. The objective of this study is to conduct a systematic review to synthesize and appraise evidence from CPGs, available worldwide, for pregnant women affected by obesity. An experienced information specialist performed a rigorous search of the literature, searching MEDLINE, Embase, grey literature, and guideline registries to locate CPGs that reported on pregnancy care relating to obesity. CPGs related to antenatal care of pregnant women with obesity (pre‐pregnancy body mass index [BMI] ≥ 30 kg/m²) in low‐risk (eg, care provider = family physician or midwife) or high‐risk settings (eg, obstetrician or maternal fetal medicine) were included. CPGs were appraised for quality with independent data collection by two raters. Information was categorized into five domains: preconception care. care during pregnancy, diet and exercise during pregnancy, care immediately before, during, and after delivery, and postpartum care. The literature search yielded 2614 unique citations. Following screening of abstracts and full texts, 32 CPGs were included, with quality ranging between 0 and 100 on the AGREE II tool. The strongest evidence related to nutritional advice, exercise, and pregnancy risk counselling. Guidance was limited for timing of screening tests, antenatal visits and delivery, ideal postpartum care, and management of adverse pregnancy outcomes. Most guidelines in this population are not evidence based. Research is needed to bridge knowledge gaps pertaining to fetal antenatal surveillance, management of adverse outcomes and postpartum care, and enhance consistency across CPGs.     

Implementation of asthma clinical practice guidelines in primary care: A cross-sectional study based on the Knowledge-to-Action Cycle

Objective: Based on the Knowledge-to-Action Cycle, we assessed the self-reported implementation and perception of asthma clinical practice guideline (CPG) recommendations in primary care physicians (PCPs), along with the barriers and facilitators to CPG use in primary care. Methods: We conducted a cross-sectional study. Using the extended Asthma Physicians' Practice Assessment Questionnaire^©, PCPs self-reported the following: their knowledge of 15 key asthma CPG recommendations, the perceived usefulness of each of these recommendations, their motivation to apply these recommendations, and their agreement with the content of these recommendations. Participants also reported the barriers and facilitators to CPG use in primary care. Results: Out of the 46 potential participants, 43 physicians completed the questionnaire (response rate: 93%). Results underlined care gaps regarding the provision of asthma education and written action plans, inhaler technique demonstrations, and assessment of patients' concerns. Results showed that the majority of physicians knew the key asthma CPG recommendations, but their motivation to implement them and the perceived usefulness of these recommendations varied from one proposal to another. Main barriers to the implementation of these recommendations were related to time and resources. PCPs stressed the importance of teamwork for enhancing the use of asthma CPGs in primary care. Conclusions: Our results suggest that the implementation of asthma CPGs remains suboptimal in primary care. Interventions addressing the identified barriers and providing facilitators to asthma CPG implementation, such as continuing education, could be implemented and evaluated to sustain asthma CPG use in primary care settings.     

Worldwide guidelines for chronic obstructive pulmonary disease: a comparison of diagnosis and treatment recommendations

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of worldwide burden of disease, but is underdiagnosed and undertreated. We performed a systematic review of worldwide COPD clinical practice guidelines (CPG) to determine the degree of international consensus on major guideline recommendations. METHODS: The COPD CPG were identified from the medical literature and through contact with respiratory experts and organizations. An abstraction form was developed to collect information related to COPD diagnosis and management. RESULTS: Locally developed COPD CPG are based upon expert consensus, but do not explicitly rate the strength of the evidence for recommendations. The detail and clarity of the 41 CPG varied regarding the diagnosis and management of COPD. Key differences included the lung function parameters that define a diagnosis and severity assignment of COPD. The use of anticholinergics, alone or in combination, was listed as a consideration for first-line therapy for persistent COPD in all 41 CPG. There was consensus regarding reserving corticosteroids for selected patients. CONCLUSIONS: There is variation and ambiguity within COPD CPG regarding specific recommendations that can be applied by clinicians at a patient-specific level. The variation in CPG for COPD may contribute to the underdiagnosis and suboptimal treatment of COPD. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop report may help resolve some of the variation surrounding COPD diagnosis and treatment. However, local guideline implementation efforts must assist physicians in applying guideline recommendations to support patient-specific management.     

Quantity and quality of complementary and alternative medicine recommendations in clinical practice guidelines for type 2 diabetes mellitus: A systematic review

AimsApproximately 70% of Americans with diabetes have used complementary and alternative medicine (CAM) in the past year. Healthcare providers often receive minimal training on these therapies and subsequently rely on clinical practice guidelines (CPGs) to supplement their knowledge about the safe and effective use of CAM for the treatment/management of type 2 diabetes mellitus (T2DM). The purpose of this systematic review is to determine the quantity and assess the quality of CAM recommendations in CPGs for the treatment and/or management of T2DM.Data synthesisMEDLINE, EMBASE, and CINAHL were systematically searched from 2009 to 2020, in addition to the Guidelines International Network and the National Center for Complementary and Integrative Health websites. CPGs containing treatment and/or management recommendations for T2DM were eligible; those with CAM recommendations were quality-assessed with the AGREE II instrument twice, once for the overall CPG and once for the CAM sections. Twenty-seven CPGs were deemed eligible, of which 7 made CAM recommendations. Mean scaled domain percentages were (overall, CAM): scope and purpose (89.7%, 79.8%), clarity of presentation (85.7%, 48.4%), stakeholder involvement (67.9%, 28.2%), applicability (54.8%, 20.2%), rigour of development (49.7%, 35.7%), and editorial independence (44.1%, 44.1%).ConclusionsQuality varied within and across CPGs; domain scores across CAM sections generally scored lower than the overall CPG. Given that CAM therapies for T2DM are only represented in one-quarter of eligible CPGs and are of lower quality, a knowledge gap exists for healthcare providers who seek evidence-based information on this topic in order to effectively counsel inquiring patients.     

Diabetes-Specific Nutrition Algorithm: A Transcultural Program to Optimize Diabetes and Prediabetes Care

Type 2 diabetes (T2D) and prediabetes have a major global impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. To mitigate this disease burden, interventions of proven effectiveness must be used. Evidence shows that nutrition therapy improves glycemic control and reduces the risks of diabetes and its complications. Accordingly, diabetes-specific nutrition therapy should be incorporated into comprehensive patient management programs. Evidence-based recommendations for healthy lifestyles that include healthy eating can be found in clinical practice guidelines (CPGs) from professional medical organizations. To enable broad implementation of these guidelines, recommendations must be reconstructed to account for cultural differences in lifestyle, food availability, and genetic factors. To begin, published CPGs and relevant medical literature were reviewed and evidence ratings applied according to established protocols for guidelines. From this information, an algorithm for the nutritional management of people with T2D and prediabetes was created. Subsequently, algorithm nodes were populated with transcultural attributes to guide decisions. The resultant transcultural diabetes-specific nutrition algorithm (tDNA) was simplified and optimized for global implementation and validation according to current standards for CPG development and cultural adaptation. Thus, the tDNA is a tool to facilitate the delivery of nutrition therapy to patients with T2D and prediabetes in a variety of cultures and geographic locations. It is anticipated that this novel approach can reduce the burden of diabetes, improve quality of life, and save lives. The specific Southeast Asian and Asian Indian tDNA versions can be found in companion articles in this issue of Current Diabetes Reports.     

Misconceptions, challenges, uncertainty, and progress in guideline recommendations

Although the quality of clinical practice guidelines has improved over the last decade, current guideline systems have limitations that reduce their validity and limit their acceptance. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group, a worldwide collaboration of guideline developers, methodologists, and clinicians, has constructed a system for developing guidelines that addresses these shortcomings. The system includes a transparent and rigorous methodology for rating the quality of evidence, an explicit balancing of benefits and harms of healthcare interventions, an explicit acknowledgement of the values and preferences that underlie the recommendations, and whether the intervention represents a wise use of resources. These four elements determine whether a recommendation is strong or weak. A guideline panel offers strong recommendations when virtually all informed patients would choose the same management strategy. Weak recommendations imply that choices will differ across the range of patient values and preferences. The GRADE system has been tested in multiple practice settings and for a large spectrum of questions, refined and re-evaluated to ensure that it captures the complex issues involved in evidence assessment and grading recommendations while maintaining simplicity and practicality. Many guideline organizations and medical societies have endorsed the system and adopted it for their guideline processes.