GRADE Guidance Research Articles

Simultaneous evaluation of the imprecision and inconsistency domains of GRADE can be performed using prediction intervals

ObjectivesTo explore the use of prediction interval (PI) for the simultaneous evaluation of the imprecision and inconsistency domains of Grading of Recommendations, Assessment, and Evaluation using stakeholder-provided decision thresholds. Study Design and SettingWe propose transforming the PI of a meta-analysis from a relative risk scale to an absolute risk difference using an appropriate baseline risk. The transformed PI is compared to stakeholder-provided thresholds on an absolute scale. We applied this approach to a large convenience sample of meta-analyses extracted from the Cochrane Database of Systematic Reviews and compared it against the traditional approach of rating imprecision and inconsistency separately using confidence intervals and statistical measures of heterogeneity, respectively. We used empirically derived thresholds following Grading of Recommendations, Assessment, and Evaluation guidance. ResultsThe convenience sample consisted of 2516 meta-analyses (median of 7 studies per meta-analysis; interquartile range: 5–11). The main analysis showed the percentage of meta-analyses in which both approaches had the same number of certainty levels rated down was 59%. The PI approach led to more levels of rating down (lower certainty) in 27% and to fewer levels of rating down (higher certainty) in 14%. Multiple sensitivity analyses using different thresholds showed similar results, but the PI approach had particularly increased width with a larger number of included studies and higher I2 values. ConclusionUsing the PI for simultaneous evaluation of imprecision and inconsistency seems feasible and logical but can lead to lower certainty ratings. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria. Plain Language SummaryThe prediction interval (PI) addresses both the imprecision and inconsistency domains of certainty. In this study, we applied this PI approach to simultaneously judge both domains and compared this to the traditional approach of making these separate judgments. The 2 approaches had moderate agreement. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria.

GRADE good practice statements: a time to say “good-bye”? A new typology for normative statements on interventions

BackgroundClinical and public health guidelines include a variety of types of normative statements concerning interventions. “Recommendations” are usually the central focus, and are based on one or more systematic reviews of research evidence. Guidelines may include other types of normative statements, however, including Grading of Recommendations, Assessment, Develoment, and Evaluation (GRADE) good (or best) practice statements (GPS), which represent recommendations that guideline panels feel are important but are not appropriate for formal ratings of quality of evidence because it is sufficiently obvious that desirable effects outweigh undesirable effects. These normative statements are typically supported by a great deal of high-certainty, indirect evidence, which the authors feel would be a waste of time to examine. There are a number of conceptual and methodological issues with GRADE GPS, however, and these are manifested in guidelines, including both inappropriate overuse and underuse, and unclear interpretation and impact among end-users. This situation has arisen in part from lack of clarity in, and misunderstandings of, GRADE guidance, the lumping of many different types of normative statements under one label (“GPS”), from limitations in GRADE's approach to linked bodies of evidence, and because the appropriate basis for many normative statements about interventions is not reviews of research evidence. A new typology is needed for normative statements on interventions and policies that are not optimally based on reviews of research evidence. Proposed TypologyThis proposed typology differentiates normative statements about interventions by the type or nature of the most appropriate basis for the statement. The typology encompasses the range of statements encompassed by GPS, but provides a more nuanced categorization designed to assist both guideline developers and end-users. This typology encompasses two main types of normative statements about interventions (including policies): (1) statements that indicate when to use (or not) an intervention, which intervention to use, and if, when and how to use it and (2) the principles, practices, or norms that inform or underpin such interventions. These correspond to normative statements based on empirical evidence, and those based on human rights, ethics, or norms, respectively. Normative statements based on empirical evidence include: (1) recommendations based on systematic reviews of human or animal evidence on effectiveness and harms, including linked bodies of evidence; (2) normative statements based on scientific fundamentals (eg, physical/biological/chemical properties, theories, laws, or principles); and (3) implementation guidance based most commonly on experiential evidence such as case studies. Normative statements based on human rights, ethics, or norms include: (1) guiding principles, based on human rights standards and conventions and/or ethics principles; and (2) practice norms and standards, based on clinical and public health norms and/or professional standards. ConclusionThere are conceptual and methodological problems with GRADE GPS, leading to their misapplication, with overuse and underuse. This paper presents a proposal for a new typology for normative statements on interventions, according to the basis for the statement. This typology encompasses and replaces GPS, providing a more nuanced set of statements. Testing of this proposed approach is needed among both guideline developers and end-users.

Yarışmacı Eğitim Yaklaşımının Öğrencilere Etkisine İlişkin Öğretmen Görüşleri

The purpose of this study is to determine teachers' opinions regarding the impact of competitive education approach - practices - on students' social and emotional development. Qualitative method was preferred in the research study and interview technique was used. Criterion sampling, one of the purposeful sampling methods, was used when determining the participants. The participants consist of 20 teachers who work in Sincan district of Ankara province in the 2022-2023 academic year, vary in terms of demographic characteristics, teach 12th grade students, and have worked for at least 5 years. In this study, a semi-structured interview form was created as a data collection tool to examine the social and emotional development of students in competitive education in terms of teachers' opinions, and was applied remotely via Google form. The answers given to the interview form in the study were analyzed with the content analysis method used in qualitative studies. The findings were coded and interpreted by creating themes. The classroom guidance program of the Ministry of National Education includes competencies in three development areas of students: academic, career and social and emotional. Social and emotional development area; It consists of ensuring personal safety, self-awareness, interpersonal skills, understanding and managing emotions, and decision-making competencies. As a result of our study, in which we discussed the effect of the competitive education approach, which is the purpose of our research, on the social and emotional development of students in the context of the social and emotional development competencies of the 12th grade guidance program, it can be said that the competitive education approach is insufficient to realize the social and emotional development of students at the desired level. While protecting personal security, self-awareness, interpersonal relations and decision-making skills show development in the social field, understanding and managing emotions show emotional development. At the end of the research, comparative practices that support emotional development can be determined by universities, and it can be recommended to provide consultancy services to the Ministry of Education and schools, to support the social development of students by school-family cooperation for each student, and to be supported by school administrators. Keywords: Competition, competitive education, social and emotional development, meritocracy

Safety and efficacy of beta-3 adrenergic agonists in treating neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

To evaluate efficacy and safety of beta-3 adrenergic agonists in adults with neurogenic lower urinary tract dysfunction. According to a protocol (CRD42022350079), we searched multiple data sources for published and unpublished randomized controlled trials (RCTs) up to 2nd August 2022. Two review authors independently screened studies and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence (CoE). We found data to inform two comparisons: beta-3 adrenergic agonists versus placebo (4 RCTs) and anticholinergics (2 RCTs). Only mirabegron was used for intervention in all included studies. Compared to placebo, beta-3 adrenergic agonists may have a clinically unimportant effect on urinary symptoms score (mean difference [MD] -2.50, 95% confidence interval [CI] -4.78 to -0.22; I²=92%; 2 RCTs; 192 participants; low CoE) based on minimal clinically important difference of 3. We are very uncertain of the effects of beta-3 adrenergic agonists on quality of life (MD 10.86, 95% CI 1.21 to 20.50; I²=41%; 2 RCTs; 98 participants; very low CoE). Beta-3 adrenergic agonists may result in little to no difference in major adverse events (cardiovascular adverse events) (risk ratio 0.57, 95% CI 0.14 to 2.37; I²=0%; 4 RCTs; 310 participants; low CoE). Compared to anticholinergics, no study reported urinary symptom scores and quality of life. There were no major adverse events (cardiovascular adverse events) in either study group (1 study; 60 participants; very low CoE). Compared to placebo, beta-3 adrenergic agonists may have similar effects on urinary symptom scores and major adverse events. There were uncertainties about their effects on quality of life. Compared to anticholinergics, we are either very uncertain or have no evidence about urinary symptom scores, quality of life, and major adverse events.

Immunotherapy for advanced or metastatic urothelial carcinoma.

Immunotherapy for advanced or metastatic urothelial carcinoma.

GRADE guidance 38: updated guidance for rating up certainty of evidence due to a dose-response gradient

IntroductionThis updated guidance from the Grading of Recommendations Assessment, Development, and Evaluation addresses rating up certainty of evidence due to a dose-response gradient (DRG) observed in synthesis of intervention and exposure studies. Study Design and SettingThis guidance was developed using iterative discussions and consensus in multiple meetings and was presented to attendees of the Grading of Recommendations Assessment, Development, and Evaluation Working Group meeting for feedback in November 2022 and for final approval in May 2023. ResultsThe guidance consists of two steps. The first is to determine whether the DRG is credible. We describe five items for assessing credibility: a) is DRG identified using a proper analytical approach; b) is confounding the cause of the DRG; c) is there serious concern about ecological bias; d) is the DRG consistent across studies; and e) is there indirect evidence supporting the DRG. The first two of these items are the most critical. If the DRG was judged to be credible, then the second step is to apply the DRG domain and consider rating up, but only by one level due to the concern about residual confounding. ConclusionSystematic review authors should only rate up certainty in evidence when a DRG is deemed credible.

The development methods of official GRADE articles and requirements for claiming the use of GRADE – A statement by the GRADE guidance group

One of the aims of the GRADE Working Group has been to develop a single system that would reduce confusion arising from a legion of multiple conflicting systems for grading evidence and recommendations and serve as unifying lingua franca. Although GRADE has been widely endorsed, the way it is being used is not infrequently inconsistent with GRADE guidance and some groups have modified the approach. Based on the suggested criteria for claiming the use and application of GRADE that are available on the GWG website since 2008, we propose seven items that should be met in order to appropriately claim that the GRADE approach was used. These requirements apply to, either assessing certainty of evidence (e.g., in systematic reviews or health technology assessments) and developing recommendations (e.g., in guidelines) or making health care decisions (e.g., coverage, public health or health systems). They include how the certainty of a body of evidence is defined, assessed for each critical outcome using the GRADE domains, and presented. Furthermore, they suggest that explicit criteria (both health related and contextual) and evidence as described in the Evidence to Decision (EtD) frameworks should form the basis for recommendations or decisions and explicit judgements should be made for each criterion that is chosen for the EtD process. A recommendation should have one of two strengths (strong or conditional, also called weak) and one of two directions (for or against). Given these suggested minimal requirements in this article, we also provide a detailed description of the GRADE Working Group’s current methods and processes for developing official GRADE guidance and concepts, as well as by whom and how they are authored.

Fosfomycin for Antibiotic Prophylaxis in Men Undergoing a Transrectal Prostate Biopsy: A Systematic Review and Meta-Analysis.

Background and Objectives: To assess the effects of fosfomycin compared with other antibiotics as a prophylaxis for urinary tract infections (UTIs) in men undergoing transrectal prostate biopsies. Materials and Methods: We searched multiple databases and trial registries without publication language or status restrictions until 4 January 2022. Parallel-group randomized controlled trials (RCTs) and non-randomized studies (NRS) were included. The primary outcomes were febrile UTI, afebrile UTI, and overall UTI. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs. The protocol was registered with PROSPERO (CRD42022302743). Results: We found data on five comparisons; however, this abstract focuses on the primary outcomes of the two most clinically relevant comparisons. Regarding fosfomycin versus fluoroquinolone, five RCTs and four NRSs with a one-month follow-up were included. Based on the RCT evidence, fosfomycin likely resulted in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to four fewer febrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in afebrile UTIs compared with fluoroquinolone. This difference corresponded to 29 fewer afebrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in overall UTIs compared with fluoroquinolone. This difference corresponded to 35 fewer overall UTIs per 1000 patients. Regarding fosfomycin and fluoroquinolone combined versus fluoroquinolone, two NRSs with a one- to three-month follow-up were included. Based on the NRS evidence, fosfomycin and fluoroquinolone combined may result in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to 16 fewer febrile UTIs per 1000 patients. Conclusions: Compared with fluoroquinolone, fosfomycin or fosfomycin and fluoroquinolone combined may have a similar prophylactic effect on UTIs after a transrectal prostate biopsy. Given the increasing fluoroquinolone resistance and its ease to use, fosfomycin may be a good option for antibiotic prophylaxis.

Dose-escalated radiotherapy for clinically localized and locally advanced prostate cancer.

Dose-escalated radiotherapy for clinically localized and locally advanced prostate cancer.

Exploring state department of education grading guidance during COVID-19: A model for future emergency remote learning

Due to the COVID-19 pandemic, many United States brick-and-mortar schools in Spring 2020 rapidly transitioned to emergency remote learning. School leaders grappled with how grades ought to fit within the many unknowns of K-12 remote education. In some cases, schools modified their grading scales to give students greater flexibility to pass courses, and in other situations, schools offered incomplete grades in lieu of failures. During this time, state departments of education (DOEs) provided a variety of guidance documents to their school districts. The purpose of this study was to explore the components of state DOE grading guidance during the Spring 2020 school shutdown, along with the patterns of guidance across states. The researchers applied a grounded theory approach to systematically explore the equivalent of 1,444 pages of documents from 48 state DOE guidelines. The document analysis resulted in three primary categories that influenced state DOE grading guidance: guiding principles, student advancement, and determining grades. The researchers conclude by presenting and discussing a three-category model for emergency remote learning grading guidelines for K-12 schools. In the event of another pandemic temporarily affecting the delivery of education to students, policymakers may use this model as a starting point for future recommendations.

Strong and high-quality evidence synthesis needs Cochrane: a statement of support by the GRADE Guidance Group

Cochrane is widely recognized for its pioneering efforts in promoting and producing high quality systematic reviews as the basis of evidence-based decision-making and advancing the underlying methods of evidence synthesis. The GRADE Working Group has developed the most widely used approach to rating the certainty of evidence, to ensure that users of the reviews understand how much trust to put in findings of research and to then use this evidence for decision-making.For decades, both organizations have been closely aligned through their mutual goal of providing trustworthy healthcare related information to allow individuals, guideline developers, and policy makers to make decisions grounded in evidence.Beyond the concepts of SoF table, the joint experience in rating the certainty of evidence and the application of GRADE in Cochrane reviews strengthened the reviews and GRADE’s conceptual developments, and, ultimately, becoming the internationally accepted approach for rating certainty of evidence.The work of the two groups is also aligned with the mission of the Journal of Clincial Epidemiology’s (JCE) promotion of the quality of clinical and patient-oriented health care research. These alignments are one of the reasons for submitting this commentary to the JCE in support of Cochrane.A strong Cochrane is not only in the interest of GRADE and the entire evidence-based healthcare community, but also of the future of trusted evidence, informed decisions, and a better health.

GRADE guidance 35: update on rating imprecision for assessing contextualized certainty of evidence and making decisions

ObjectivesGrading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to rate the certainty domain of imprecision is presently not fully operationalized for rating down by two levels and when different baseline risk or uncertainty in these risks are considered. In addition, there are scenarios in which lowering the certainty of evidence by three levels for imprecision is more appropriate than lowering it by two levels. In this article, we conceptualize and operationalize rating down for imprecision by one, two and three levels for imprecision using the contextualized GRADE approaches and making decisions. MethodsThrough iterative discussions and refinement in online meetings and through email communication, we developed draft guidance to rating the certainty of evidence down by up to three levels based on examples. The lead authors revised the approach according to the feedback and the comments received during these meetings and developed GRADE guidance for how to apply it. We presented a summary of the results to all attendees of the GRADE Working Group meeting for feedback in October 2021 (approximately 80 people) where the approach was formally approved. ResultsThis guidance provides GRADE's novel approach for the considerations about rating down for imprecision by one, two and three levels based on serious, very serious and extremely serious concerns. The approach includes identifying or defining thresholds for health outcomes that correspond to trivial or none, small, moderate or large effects and using them to rate imprecision. It facilitates the use of evidence to decision frameworks and also provides guidance for how to address imprecision about implausible large effects and trivial or no effects using the concept of the ‘review information size’ and for varying baseline risks. The approach is illustrated using practical examples, an online calculator and graphical displays and can be applied to dichotomous and continuous outcomes. ConclusionIn this GRADE guidance article, we provide updated guidance for how to rate imprecision using the partially and fully contextualized GRADE approaches for making recommendations or decisions, considering alternate baseline risks and for both dichotomous and continuous outcomes.

GRADE guidance 24 optimizing the integration of randomized and non-randomized studies of interventions in evidence syntheses and health guidelines

Background and ObjectiveThis is the 24th in the ongoing series of articles describing the GRADE approach for assessing the certainty of a body of evidence in systematic reviews and health technology assessments and how to move from evidence to recommendations in guidelines. MethodsGuideline developers and authors of systematic reviews and other evidence syntheses use randomized controlled studies (RCTs) and non-randomized studies of interventions (NRSI) as sources of evidence for questions about health interventions. RCTs with low risk of bias are the most trustworthy source of evidence for estimating relative effects of interventions because of protection against confounding and other biases. However, in several instances, NRSI can still provide valuable information as complementary, sequential, or replacement evidence for RCTs. ResultsIn this article we offer guidance on the decision regarding when to search for and include either or both types of studies in systematic reviews to inform health recommendations. ConclusionThis work aims to help methodologists in review teams, technology assessors, guideline panelists, and anyone conducting evidence syntheses using GRADE.

GRADE guidelines 33: Addressing imprecision in a network meta-analysis

ObjectiveThis article describes GRADE guidance for assessing imprecision when rating the certainty of the evidence from network meta-analysis. Study Design and SettingA project group within the GRADE working group conducted iterative discussions, computer simulations, and presentations at GRADE working group meetings to produce and obtain approval for this guidance. ResultsWhen addressing imprecision of a network estimate, reviewers should consider the 95% confidence or credible interval, and the optimal information size. If the 95% confidence or credible interval crosses a pre-specified threshold, reviewers should rate down the certainty of the evidence. If the 95% confidence interval does not cross any pre-specfied threshold, reviewers should consider the optimal information size. Because addressing the optimal information size may be challenging, reviewers can use the effect size to decide if any calculations are necessary. When the size of the effect is modest or the optimal information size is met, reviewers should not rate down for imprecision. ConclusionReviewers should use this guidance when to appropriately address imprecision in the context of the assessment of certainty of evidence from network meta-analysis.

Update on the JCE GRADE series and other GRADE article types

JCE has introduced a new series called GRADE Notes. This commentary concerning these GRADE Notes is an official communication from JCE and the GRADE Guidance Group, the 12 individuals who act on behalf of the GRADE Working Group. The GRADE Working Group publishes official guidance articles and concept articles related to GRADE. GRADE guidance articles (previous called GRADE Guidelines)[ [1] Guyatt G Oxman AD Akl EA Kunz R Vist G Brozek J et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011; 64 (Apr): 383-394 Abstract Full Text Full Text PDF PubMed Scopus (4535) Google Scholar ] typically include "how to use GRADE" information supplemented with examples. GRADE concept articles discuss concepts (e.g., new ways of defining certainty of evidence) that may not have been piloted on examples and that may not necessarily result in GRADE guidance. However, GRADE concept articles are intended to further develop an area relevant to assessing the certainty in evidence and/or supporting recommendations. These articles explicitly discuss the concept that relates to GRADE and how it relates to existing GRADE domains, criteria, and guidance. Several GRADE concept articles have been published and the JCE recently began a new numbering system to separate Guidance from Concept articles.[ [2] Pottie K Magwood O Rahman P Concannon T Alonso-Coello P JaramilloGarcia A et al. GRADE Concept Paper 1: Validating the "F.A.C.E" instrument using stakeholder perceptions of feasibility, acceptability, cost, and equity in guideline implement. J Clin Epidemiol. 2021; 131 (Mar): 133-140 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ] GRADE Guidance and Concept articles have been formally approved by the GRADE Working Group after a process of drafting articles, presentations at GRADE Working Group meetings, revisions and voting by members of the GRADE Working Group.

GRADE Guidance: 31. Assessing the certainty across a body of evidence for comparative test accuracy

ObjectivesThis article provides GRADE guidance on how authors of evidence syntheses and health decision makers, including guideline developers, can rate the certainty across a body of evidence for comparative test accuracy questions. Study design and settingThis guidance extends the previously published GRADE guidance for assessing certainty of evidence for test accuracy to scenarios in which two or more index tests are compared. Through an iterative brainstorm-discussion-feedback process within the GRADE working group, we developed a guidance accompanied by practical examples. ResultsRating the certainty of evidence for comparative test accuracy shares many concepts and ideas with the existing GRADE guidance for test accuracy. The rating in comparisons of test accuracy requires additional considerations, such as the selection of appropriate comparative study designs, additional criteria for judging risk of bias, and the consequences of using comparative measures of test accuracy. Distinct approaches to rating certainty are required for comparative test accuracy studies and between-study (indirect) comparisons. ConclusionThis GRADE guidance will support transparent assessment of the certainty for a body of comparative test accuracy evidence.

Evaluation by students of bibliotherapy technique used in group guidance activities

The purpose of the study is to evaluate the views of psychological counseling and guidance students on the impact of structured bibliotherapy application on their social and emotional skills. The research was conducted through a case study, interviews and content analysis. The study group of the research consisted of 30 people from the 3rd grade psychological counseling and guidance students studying at the Faculty of Education of a private university in Cyprus in the 2017-18 academic year. According to the results obtained from the study, it is seen that psychological counseling and guidance department students underline that the tales used in bibliotherapy supported group guidance activities are didactic, educative, impressive, instructive and awareness-raising. In addition, it was observed that the students of the psychological counseling and guidance department agreed that their social emotional gains in bibliotherapy supported group counseling activities strengthened communication, contributed to their ability to look at different perspectives, to think more broadly, to get rid of prejudices, and to possess empathic thinking skills.

Prostatic arterial embolization for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

Prostatic arterial embolization for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

Brain tumor segmentation using 3D Mask R-CNN for dynamic susceptibility contrast enhanced perfusion imaging

The segmentation of neoplasms is an important part of radiotherapy treatment planning, monitoring disease progression, and predicting patient outcome. In the brain, functional magnetic resonance imaging (MRI) like dynamic susceptibility contrast enhanced (DSCE) or T1-weighted dynamic contrast enhanced (DCE) perfusion MRI are important tools for diagnosis. They play a crucial role in providing pre-operative assessment of tumor histology, grading, and biopsy guidance. However, the manual contouring of these neoplasms is tedious, expensive, time-consuming, and vulnerable to inter-observer variability. In this work, we propose a 3D mask region-based convolutional neural network (R-CNN) method to automatically segment brain tumors in DSCE MRI perfusion images. As our goal is to simultaneously localize and segment the tumor, our training process contained both a region-of-interest (ROI) localization and regression with voxel-wise segmentation. The combination of classification loss, ROI location and size regression loss, and segmentation loss were used to supervise the proposed network. We retrospectively investigated 21 patients’ perfusion images, with between 50 and 70 perfusion time point volumes, a total of 1260 3D volumes. Tumor contours were automatically segmented by our proposed method and compared against other state-of-the-art methods and those delineated by physicians as the ground truth. The results of our method demonstrated good agreement with the ground truth contours. The average DSC, precision, recall, Hausdorff distance, mean surface distance (MSD), root MSD, and center of mass distance were 0.90 ± 0.04, 0.91 ± 0.04, 0.90 ± 0.06, 7.16 ± 5.78 mm, 0.45 ± 0.34 mm, 1.03 ± 0.72 mm, and 0.86 ± 0.91 mm, respectively. These results support the feasibility of our method in accurately localizing and segmenting brain tumors in DSCE perfusion MRI. Our 3D Mask R-CNN segmentation method in DSCE perfusion imaging has great promise for future clinical use.

GRADE guidelines: 21 part 1. Study design, risk of bias, and indirectness in rating the certainty across a body of evidence for test accuracy

ObjectivesThis article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can assess the results and the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA). Study Design and SettingWe present an overview of the GRADE approach and guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests. Part 1 of the two parts in this 21st guidance article about how to apply GRADE focuses on understanding study design issues in test accuracy, provide an overview of the domains, and describe risk of bias and indirectness specifically. ResultsSupplemented by practical examples, we describe how raters of the evidence using GRADE can evaluate study designs focusing on tests and how they apply the GRADE domains risk of bias and indirectness to a body of evidence of TA studies. ConclusionRating the certainty of a body of evidence using GRADE in Cochrane and other reviews and World Health Organization and other guidelines dealing with in TA studies helped refining our approach. The resulting guidance will help applying GRADE successfully for questions and recommendations focusing on tests.