Applying GRADE for diagnosis revealed methodological challenges: an illustrative example for guideline developers

Objective: To identify challenges in the application of GRADE for diagnosis when assessing the certainty of evidence in the test-treatment strategy (diagnostic accuracy, test burden, management effectiveness, natural course, linked evidence) in an illustrative example and to propose solutions to these challenges. Study Design and Setting: A case study in applying GRADE for diagnosis that looked at the added value of IgE for diagnosing allergic rhinitis. Results: Evaluation of the full test-treatment strategy showed a lack of (high-quality) evidence for all elements. In our example, we found a lack of evidence for test burden, natural course, and link between the test result and clinical management. Overall, systematically reviewing the evidence for all elements of a test-treatment strategy is more time-consuming than only considering test accuracy results and management effectiveness. For increasing efficiency, the guideline panel could determine critical elements of the test-treatment strategy that need a systematic review of the evidence. For less critical elements, a guideline panel can rely on gray literature and professional expertise. Conclusion: A lack of high-quality evidence and time investment if the full test-treatment strategy is assessed, creating challenges in applying GRADE for diagnosis. Discussion within guideline panels about critical elements that need to be reviewed might help.