Table 6.

Adapted QUADAS-2 score form

Signaling question	Signaling question	Risk of bias	Concerns about applicability
Domain 1: Patient selection
Was a consecutive or random sample of patients enrolled?	Did the study avoid inappropriate exclusions?	Could the selection of patients have introduced bias?	Are there concerns that the included patients and setting do not match the review question?
Yes: If all consecutive or random samples of subjects were enrolled. No: If subjects were nonrandomly selected. Unclear: If sampling method was unclear.	Yes: If there were no inappropriate exclusion criteria or patients were excluded with appropriate arguments. No: If subjects were excluded based on inappropriate criteria or with inappropriate arguments. Unclear: If selection criteria were unclear	Low risk: If all signaling questions answered ‘yes’. High risk: If ‘no’ was reported for at least one signaling question, or if ‘unclear was reported for more than one signaling question. Unclear risk: If ‘unclear’ was reported for one signaling question.	Low concern: If selected subjects matched the review question and inappropriate exclusions were avoided. High concern: If selected subjects differed from those in the review question. Unclear concern: If there was insufficient information on included subjects and setting.
Domain 2: Index test
Were the index test results interpreted without knowledge of the results of the reference standard?	Physicians who performed the index test had appropriate training or the first patients were excluded for the learning curve.	Could the conduct or interpretation of the index test have introduced bias?	Are there concerns that the index test, its conduct, or interpretation differ from the review question?
Yes: If the index test results were interpreted without knowledge of the histopathological analysis of surgical specimen or when surgical biopsy only was offered based on index test results. No: If the index test results were interpreted with knowledge of the histopathological analysis of surgical specimen. Unclear: If it was unclear whether index test results were interpreted independently of the histopathological analysis of surgical specimen.	Yes: If an appropriate training for the physicians was defined or the first patients were excluded for the learning curve. No: If physicians had no appropriate training or no patients were excluded for the learning curve. Unclear: If it was unclear whether the physicians had an appropriate training or patients were excluded for the learning curve.	Low risk: If all signaling questions answered ‘yes’. High risk: If ‘no’ was reported for at least one signaling question, or if ‘unclear was reported for more than one signaling question. Unclear risk: If ‘unclear’ was reported for one signaling question.	Low concern: If the index test was performed as described in the review question. High concern: If the index test differed from those specified in the review question. Unclear concern: If there was insufficient information available
Domain 3: Reference standard
Is the reference standard likely to correctly classify the target condition?	Were patients who did not receive the reference standard specified?	Could the reference standard, its conduct, or its interpretation have introduced bias?	Are there concerns that the target condition as defined by the reference standard does not match the review question?
Yes: All patients received histopathological analysis of surgical specimen. No: Some or all patients received any other reference standard or no reference standard. Unclear: Reference standard is not stated.	Yes: If the reference standard was recommended for all malignant lesions and High Risk lesions, but was refrained with appropriate arguments. No: If the reference standard was not offered or without appropriate arguments. Unclear: Exclusions were not stated.	Low risk: If all signaling questions answered ‘yes’. High risk: If ‘no’ was reported for at least one signaling question, or if ‘unclear was reported for more than one signaling question. Unclear risk: If ‘unclear’ was reported for one signaling question.	Low concern: If pathological analysis of surgical specimen or mammographic follow-up was used. High concern: If pathological analysis of surgical specimen or mammographic follow-up was not used. Unclear concern: If insufficient information was provided in the report.
Domain 4: Flow and timing
Did all patients receive the reference standard?	Were all patients included in the analysis?	Could the patient flow have introduced bias?
Yes: If all eligible subjects with a malignant lesion or high risk lesion received surgical biopsy. No: If not all eligible subjects received the reference standard. Unclear: If this was not clear from the report.	Yes: If all subjects recruited to the study with reference standard results were included in the analysis. No: If not all recruited subjects with reference standard results were included in the analysis. Unclear: If this was unclear from the report	Low risk: If all signaling questions answered „yes. High risk: If ‘no’ was reported for at least one signaling question, or if ‘unclear was reported for more than one signaling question. Unclear risk: If ‘unclear’ was reported for one signaling question.