2020 ARIA CARE PATHWAYS FOR ALLERGIC RHINITIS - GEORGIA.

Allergic rhinitis is the most common chronic disease worldwide. Treatment guidelines have improved the knowledge on rhinitis and have had a significant impact on AR management. In 20 years, ARIA has considerably evolved from the first multi-morbidity guideline in respiratory diseases to the digital transformation of health and care. Allergic rhinitis in Georgia, Next-generation ARIA-GRADE guidelines and ARIA, 2020 care pathways for Allergen Immunotherapy have been discussed in this review.

Vitamin D supplementation in primary allergy prevention: Systematic review of randomized and non-randomized studies.

BACKGROUND: To date, a systematic review of the evidence regarding the association between vitamin D and allergic diseases development has not yet been undertaken. OBJECTIVE: To review the efficacy and safety of vitamin D supplementation when compared to no supplementation in pregnant women, breastfeeding women, infants, and children for the prevention of allergies. METHODS: Three databases were searched through January 30, 2016, including randomized (RCT) and nonrandomized studies (NRS). Two reviewers independently extracted data and assessed the certainty in the body of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Among the 1932 articles identified, one RCT and four NRS were eligible. Very low certainty in the body of evidence across examined studies suggests that vitamin D supplementation for pregnant women, breastfeeding women, and infants may not decrease the risk of developing allergic diseases such as atopic dermatitis (in pregnant women), allergic rhinitis (in pregnant women and infants), asthma and/or wheezing (in pregnant women, breastfeeding women, and infants), or food allergies (in pregnant women). We found no studies of primary prevention of allergic diseases in children. CONCLUSION: Limited information is available addressing primary prevention of allergic diseases after vitamin D supplementation, and its potential impact remains uncertain.

Prebiotics for the prevention of allergies: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Prevalence of allergic diseases in infants is approximately 10% reaching 20 to 30% in those with an allergic first-degree relative. Prebiotics are selectively fermented food ingredients that allow specific changes in composition/activity of the gastrointestinal microflora. They modulate immune responses, and their supplementation has been proposed as an intervention to prevent allergies. OBJECTIVE: To assess in pregnant women, breastfeeding mothers, and infants (populations) the effect of supplementing prebiotics (intervention) versus no prebiotics (comparison) on the development of allergic diseases and to inform the World Allergy Organization guidelines. METHODS: We performed a systematic review of studies assessing the effects of prebiotic supplementation with an intention to prevent the development of allergies. RESULTS: Of 446 unique records published until November 2016 in Cochrane, MEDLINE, and EMBASE, 22 studies fulfilled a priori specified criteria. We did not find any studies of prebiotics given to pregnant women or breastfeeding mothers. Prebiotic supplementation in infants, compared to placebo, had the following effects: risk of developing eczema (RR: 0.68, 95% CI: 0.40 to 1.15), wheezing/asthma (RR, 0.37; 95% CI: 0.17 to 0.80), and food allergy (RR: 0.28, 95% CI: 0.08 to 1.00). There was no evidence of an increased risk of any adverse effects (RR: 1.01, 95% CI: 0.92 to 1.10). Prebiotic supplementation had little influence growth rate (MD: 0.92 g per day faster with prebiotics, 95% CI: 0 to 1.84) and the final infant weight (MD: 0.10 kg higher with prebiotics, 95% CI: -0.09 to 0.29). The certainty of these estimates is very low due to risk of bias and imprecision of the results. CONCLUSIONS: Currently available evidence on prebiotic supplementation to reduce the risk of developing allergies is very uncertain.

Methodology for the development of the NHF-McMaster Guideline on Care Models for Haemophilia Management.

BACKGROUND: Rigorous and transparent methods are necessary to develop clinically relevant and evidence-based practice guidelines. We describe the development of the National Hemophilia Foundation-McMaster Guideline on Care Models for Haemophilia Management, which addresses best practices in haemophilia care delivery. METHODS: We assembled a Panel of persons with haemophilia (PWH), parents of PWH, clinical experts and guideline methodologists. Conflicts of interest were disclosed and managed throughout. Panel members and key stakeholders were surveyed to develop the guideline questions and identify patient-important outcomes. Systematic reviews of the literature were conducted for all factors important in decision-making: benefits and harms; patient values and preferences; resource implications; acceptability; equity; and feasibility. We used the GRADE approach to create evidence profiles to evaluate the evidence and present key results. Evidence to Decision frameworks were created to guide the Panel in making evidence-based recommendations. When evidence was very low quality or not available, evidence from other chronic disease populations was presented to the Panel to inform the recommendations. Additionally, we systematically pooled observations from experts, and conducted qualitative interviews exploring key stakeholder experiences and perspectives. The Panel made recommendations for each guideline question and elaborated on research priorities, implementation considerations, and monitoring. Final recommendations were circulated for public and peer review. CONCLUSIONS: Despite the paucity of high-quality evidence typical of a rare condition such as haemophilia, we successfully applied a rigorous and transparent methodology based on GRADE to develop an evidence-based clinical practice guideline.

Integrated multidisciplinary care for the management of chronic conditions in adults: an overview of reviews and an example of using indirect evidence to inform clinical practice recommendations in the field of rare diseases.

BACKGROUND: Integrated care models have been adopted for individuals with chronic conditions and for persons with rare diseases, such as haemophilia. OBJECTIVE: To summarize the evidence from reviews for the effects of integrated multidisciplinary care for chronic conditions in adults and to provide an example of using this evidence to make recommendations for haemophilia care. SEARCH METHODS: We searched MEDLINE, EMBASE, CINAHL and Cochrane Database of Systematic Reviews up to January 2016, and reviewed reference lists of retrieved papers. SELECTION CRITERIA: Systematic reviews of at least one randomized study, on adults with non-communicable chronic conditions. DATA COLLECTION AND ANALYSIS: Two investigators independently assessed eligibility and extracted data. Quality of reviews was assessed using ROBIS, and the evidence assessed using GRADE. RESULTS: We included seven reviews reporting on three chronic conditions. We found low to high quality evidence. Integrated care results in a reduction in mortality; likely a reduction in emergency visits and an improvement in function; little to no difference in quality of life, but shorter hospital stays; and may result in little to no difference in missed days of school or work. No studies reported educational attainment, or patient adherence and knowledge. When used for haemophilia, judgment about the indirectness of the evidence was driven by disease, intervention or outcome characteristics. CONCLUSION: This overview provides the most up to date evidence on integrated multidisciplinary care for chronic conditions in adults, and an example of how it can be used for guidelines in rare diseases.

Care models in the management of haemophilia: a systematic review.

BACKGROUND: Haemophilia care is commonly provided via multidisciplinary specialized management. To date, there has been no systematic assessment of the impact of haemophilia care delivery models on patient-important outcomes. OBJECTIVE: To conduct a systematic review of published studies assessing the effects of the integrated care model for persons with haemophilia (PWH). SEARCH METHODS: We searched MEDLINE, EMBASE and CINAHL up to April 22, 2015, contacted experts in the field, and reviewed reference lists. SELECTION CRITERIA: Randomized and non-randomized studies of PWH or carriers, focusing mainly on the assessment of care models on delivery. DATA COLLECTION AND ANALYSIS: Two investigators independently screened title, abstract, and full text of retrieved articles for inclusion. Risk of bias and overall quality of evidence was assessed using Cochrane's ACROBAT-NRSI tool and GRADE respectively. Relative risks, mean differences, proportions, and means and their variability were calculated as appropriate. RESULTS: 27 non-randomized studies were included: eight comparative and 19 non-comparative studies. We found low- to very low-quality evidence that in comparison to other models of care, integrated care may reduce mortality, hospitalizations and emergency room visits, may lead to fewer missed days of school and work, and may increase knowledge seeking. CONCLUSION: Our comprehensive review found low- to very low-quality evidence from a limited number of non-randomized studies assessing the impact of haemophilia care models on some patient-important outcomes. While the available evidence suggests that adoption of the integrated care model may provide benefit to PWH, further high-quality research in the field is needed.

NHF-McMaster Guideline on Care Models for Haemophilia Management.

This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia.

MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation.

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.

Required knowledge for guideline panel members to develop healthcare related testing recommendations - a developmental study.

OBJECTIVE: To define the minimum knowledge required for guideline panel members (healthcare professionals and consumers) involved in developing recommendations about healthcare related testing. STUDY DESIGN AND SETTING: A developmental study with a multi-staged approach. We derived a first set of knowledge components from literature and subsequently performed semi-structured interviews with nine experts. We refined the set of knowledge components and checked it with the interviewees for final approval. RESULTS: Understanding the test-management pathway, e.g., how test results should be used in context of decisions about interventions, is the key knowledge component. The final list includes 26 items on the following topics: health question, test-management pathway, target population, test, test result, interpretation of test results & subsequent management, and impact on people important outcomes. For each item, the required level of knowledge is defined. CONCLUSION: We developed a list of knowledge components required for guideline panels to formulate recommendations on healthcare related testing. The list could be used to design specific training programs for guideline panel members when developing recommendations about tests and testing strategies in healthcare.

Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

Oral immunotherapy for IgE-mediated cow's milk allergy: a systematic review and meta-analysis.

Cow's milk is a common cause of food allergy in children. Children usually outgrow cow's milk allergy by the age of 3-5 years, but some will have persistent symptoms beyond childhood. We performed a systematic review of randomized controlled trials (RCTs) and observational studies to assess the evidence supporting the use of oral immunotherapy in IgE-mediated cow's milk allergy to inform the World Allergy Organization guidelines. Of 1034 screened articles published until May 2011, five RCTs and five observational studies fulfilled a priori specified inclusion criteria. RCTs including 218 patients showed that oral immunotherapy, compared to elimination diet alone, increased the likelihood of achieving full tolerance of cow's milk [relative risk: 10.0 (95% CI: 4.1-24.2)]. Adverse effects of immunotherapy include frequent local symptoms (16% of doses), mild laryngospasm [relative risk: 12.9 (1.7-98.6)], mild asthma [rate ratio: 3.8 (2.9-5.0)], reactions requiring oral glucocorticosteroids [relative risk: 11.3 (2.7-46.5)] or intramuscular epinephrine injection [rate ratio 5.8 (1.6-21.9)]. Results of observational studies were consistent with those of RCTs. Despite the availability of RCTs, the overall low quality of evidence leaves important uncertainty about anticipated effects of immunotherapy due to very serious imprecision of the estimates of effects and the likelihood of publication bias for some of the critical outcomes. A potentially large benefit of oral immunotherapy in patients with cow's milk allergy may be counterbalanced by frequent and sometimes serious adverse effects. Additional, larger RCTs measuring all patient-important outcomes are still needed.

Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

[ARIA (Allergic Rhinitis and its Impact on Asthma) achievements in 10 years and future needs]. / ARIA (allerjik rinit ve astim üzerine etkisi) 10 yildaki kazanimlar ve gelecekteki gereksinimler.

Allergic rhinitis and asthma represent global health problems for all age groups. Asthma and rhinitis frequently co-exist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization (WHO) workshop in 1999 and was published in 2001. ARIA has reclassified allergic rhinitis as mild/moderate-severe and intermittent/persistent. This classification schema closely reflects the impact of allergic rhinitis on patients. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of allergic rhinitis and asthma co-morbidities based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation). ARIA has been disseminated and implemented in over 50 countries of the world. In Turkey, it is important to make a record of ARIA achievements and to identify the still unmet clinical, research and implementation needs in order to strengthen the 2011 EU Priority on allergy and asthma in children.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations.

This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients' values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients' values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.

How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement.

Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom-medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.

Development and implementation of guidelines in allergic rhinitis ­ an ARIA-GA2LEN paper.

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

Desensitizing Toothpastes for Dentin Hypersensitivity: A Network Meta-analysis.

The goal of this systematic review and network meta-analysis was to compare the relative effects of toothpaste formulations for dentin hypersensitivity (DH), tested in randomized controlled trials (RCTs). We searched 7 databases to February 2019. Paired reviewers independently screened studies, extracted data, and performed risk of bias assessment. The outcome of interest was painful response measured through tactile, cold, and air stimuli. We conducted a random-effects Bayesian network meta-analysis using standardized mean difference (SMD) and their credible intervals (CIs) as the measure of effect for each pain stimuli. We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included 125 RCTs (12,541 patients). For tactile stimulus, the following active ingredients showed large beneficial effects compared to fluoride with moderate certainty of evidence (SMD; 95% CI): potassium + stannous fluoride (SnF2) (3.05; 1.69-4.41), calcium sodium phosphosilicate (CSP) (2.14; 0.75-3.53), SnF2 (2.02; 1.06-2.99), potassium + hydroxyapatite (2.47; 0.3-4.64), strontium (1.43; 0.46-2.41), and potassium (1.23; 0.48-1.98). For cold stimulus, CSP showed large beneficial effects compared to fluoride (3.93; 0.34-7.53) with moderate certainty; for air stimulus, arginine (2.22; 1.45-2.99), potassium + hydroxyapatite (2.44; 0.33-4.55), potassium + SnF2 (2.28; 0.87-3.69), CSP (1.98; 0.99-2.98), and SnF2 (1.9; 1.03-2.77) showed large beneficial effects compared to fluoride with moderate to high certainty. Most toothpaste formulations showed evidence of superiority against placebo or fluorides (amine fluoride, sodium monofluorophosphate, or sodium fluoride). CSP was most beneficial for all 3 stimuli with high to moderate certainty. SnF2 alone and potassium combined with SnF2 or hydroxyapatite were beneficial for tactile and air stimulus with high to moderate certainty. Arginine was beneficial for air stimulus, and strontium and potassium were beneficial for tactile stimulus, with moderate certainty.

How to increase the value of randomised trials in COPD research.

Methodological criteria that increase the validity of randomised trials are often not considered in respiratory research, even in large chronic obstructive pulmonary disease (COPD) trials. We describe four important aspects in the design, analysis and reporting of randomised trials, selected based on their relevance to current COPD research and based on our judgments of importance for researchers and users of the literature. First, to optimally control for confounding, where confounding refers to a factor that is associated with an exposure or intervention and influences the outcome, a clear definition of the main relationship between treatment and the primary outcome as well as identification of measurable confounders is required. In addition to randomisation per se as the key method to protect against confounding, restriction (excluding patients with specific characteristics that may introduce confounding), stratification (separate randomisation of patients with specific characteristics) and statistical adjustment are means to be considered to optimally control for confounding that simple randomisation may not achieve. Secondly, the selection of the primary outcome should be guided by the importance to patients. Secondary outcomes provide hypotheses about the effects observed for the primary outcome and can provide important data for systematic reviews and meta-analyses, but should be interpreted with caution in single trials. Thirdly, in study power calculations, not only the actual sample size, but the number of events, has a large influence on the power of the study and, often, unrealistic assumptions about event rates are made to increase the feasibility of trials. Finally, essential steps to transfer results from research to practice include complete reporting of trials and developing tools, such as decision aids, to support patients and physicians in their shared decision making.

Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 1 of 3. An overview of the GRADE approach and grading quality of evidence about interventions.

The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach provides guidance to grading the quality of underlying evidence and the strength of recommendations in health care. The GRADE system's conceptual underpinnings allow for a detailed stepwise process that defines what role the quality of the available evidence plays in the development of health care recommendations. The merit of GRADE is not that it eliminates judgments or disagreements about evidence and recommendations, but rather that it makes them transparent. This first article in a three-part series describes the GRADE framework in relation to grading the quality of evidence about interventions based on examples from the field of allergy and asthma. In the GRADE system, the quality of evidence reflects the extent to which a guideline panel's confidence in an estimate of the effect is adequate to support a particular recommendation. The system classifies quality of evidence as high, moderate, low, or very low according to factors that include the study methodology, consistency and precision of the results, and directness of the evidence.