Table 1.

Structure of the QUADAS-2 tool²²

Domain	Risk of bias		Concerns regarding applicability
1. Patient selection	Was a consecutive or random sample of patients enrolled?	Yes/no/unclear	Is there concern that the included patients do not match the review question?	Concern: low/high/unclear
	Was a case–control design avoided?	Yes/no/unclear
	Did the study avoid inappropriate exclusions?	Yes/no/unclear
	Could the selection of patients have introduced bias?	Risk: low/high/unclear
2. Index test(s)	Were the index test results interpreted without knowledge of the results of the reference standard?	Yes/no/unclear	Is there concern that the index test, its conduct, or interpretation differs from the review question?	Concern: low/high/unclear
	If a threshold was used, was it prespecified?	Yes/no/unclear
	Could the conduct or interpretation of the index test results have introduced bias?	Risk: low/high/unclear
3. Reference standard*	Is the reference standard likely to correctly classify the target condition?	Yes/no/unclear	Is there concern that the target condition as defined by the reference standard does not match the review question?	Concern: low/high/unclear
	Were the reference standard results interpreted without knowledge of the results of the index test?	Yes/no/unclear
	Could the reference standard, its conduct, or its interpretation have introduced bias?	Risk: low/high/unclear
4. Flow and timing	Was there an appropriate interval between the index test and reference standard?	Yes/no/unclear
	Did all patients receive a reference standard?	Yes/no/unclear
	Did patients receive the same reference standard?	Yes/no/unclear
	Were all patients included in the analysis?	Yes/no/unclear
	Could the patient flow have introduced bias?	Risk: low/high/unclear

*Here equivalent to outcome.