250 In practice, both overuse and underuse of tests are common, and this can have a significant impact. For example, laboratory diagnostics accounts for approximately 2% of healthcare spending, yet it influences 64-67% of clinical decisions. Incorrect testing can result in high healthcare costs, unnecessary test burden, and anxiety. Developing guidelines on healthcare related testing presents several challenges. These include formulating key questions that incorporate people-important outcomes, searching and synthesising evidence, interpreting test accuracy measures, and formulating recommendations. This thesis focuses on challenges and solutions in the development of guideline recommendations about healthcare related testing, with specific attention to the required knowledge for developing these recommendations and tools to facilitate this process. The aim of this thesis is to facilitate and improve guideline development concerning healthcare related testing. This has led to the following research questions: 1. What are challenges and possible solutions when assessing the certainty of evidence of a test-management pathway? 2. Which types of evidence (diagnostic accuracy, burden of the test, natural course, treatment effectiveness, link between test result and administration of treatment) are used to support guideline recommendations about testing? 3. What is the minimum knowledge required for guideline panel members involved in developing recommendations about testing? 4. Can a step-by-step guide aid guideline developers in formulating key questions about testing? Chapter 2 addresses the first research question. This chapter analyses the added value of a test in an illustrative example. Specifically, it examines the net benefit of specific immunoglobulin E (sIgE) blood testing as an add-on test to history taking compared to history taking alone in patients suspected of having allergic rhinitis in primary care. The critical outcomes examined are relief of nasal or ocular symptoms, while the important outcomes include concentration, sleep problems, work/school absence, and quality of life. By using GRADE for diagnosis, we systematically assessed the available evidence on the elements of the test-management pathway, including test accuracy, test burden, management effectiveness, natural course, and the link between test results and management. Throughout this process, we identified challenges and proposed solutions to address them. The lack of high certainty evidence for the various elements of the test-management pathway is a major challenge in interpreting the evidence and assessing the net benefit of a test. Another major challenge is the time required to systematically evaluate the
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