38 Chapter 2 Table 4. Challenging issues and suggested solutions Challenging issue Suggested solution Lack of high-quality evidence Conduct more and/or better research, using the GRADE downgrading factors as guidance (e.g. studies with lower risk of bias, more direct studies, larger studies to decrease imprecision) [44, 45] Definition of comparison test Consider the use of the current test(s) in the clinical pathway and the proposed position of the index test when added to the clinical pathway No evidence expected in specific test burden Expand the scope and consider including grey literature or relying on patient advocates Multiple systematic reviews available for treatment effect Select reviews of at least moderate quality, taking into account PICO and search date (Very) low-quality evidence when relying on published systematic reviews about treatment Conduct a systematic review de novo if the (very) low-quality evidence is due to indirectness Lack of information in natural course studies in which there was no treatment or treatment is very unlikely Downgrade for indirectness Literature search for link between test result and clinical management Include grey literature Focus (and pre-specify) on disease-specific details (e.g. treatment adherence and treatment difficulties) Discuss within guideline panel Include qualitative research or good practice statements Definition of overall certainty in the evidence Base overall quality on elements of the test-treatment strategy that are critical to decision-making Time investment Within the guideline panel, discuss the elements for which a systematic review is relevant (i.e. the main elements that drive the decision) Diagnostic test accuracy In the test-treatment strategy, we were interested in the role of the sIgE-test as add-on test for clinical history. The challenge was how to define the comparison test. We decided to assess the accuracy of the index test compared to nasal provocation (nasal challenge), which is considered a gold standard by clinicians. Test burden We assumed not to find evidence about test burden for the specific index tests in the index population. We therefore expanded the scope to any venipuncture for diagnostic or screening purposes in adults and/or children. However, this also resulted in no aggregated evidence. A solution might be to look for and rely on grey literature or ask patient advocates or representatives, since such information might be presented in sources like textbooks rather than in scientific literature.
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