1. QUADAS‐2 classification.

Domain	Signalling question	Signalling question	Signalling question	Risk of bias	Concerns for applicability
1: Patient sampling	Was a consecutive or random sample of patients enrolled?	Was a case‐control design avoided?	Did the study avoid inappropriate exclusions?	Could the selection of participants have introduced bias?	Are there concerns that the included participants and setting do not match the review question?
	Yes: all consecutive patients or random sample of patients with focal pancreatic lesions were enrolled No: selected patients were enrolled Unclear: this was not clear from the report	Yes: case‐control design was avoided No: case‐control design was not avoided Unclear: this was not clear from the report	Yes: the study avoided inappropriate exclusions (i.e. difficult‐to‐diagnose patients) No: the study excluded patients inappropriately Unclear: this was not clear from the report	Low risk: 'yes' for all signalling questions High risk: 'no' or 'unclear' for at least 1 signalling question	Low concern: the selected participants represent the patients in whom the tests will be used in clinical practice (please see diagnostic pathway (Figure 1)) High concern: there is high concern that participant selection was performed in such a way that the included participants did not represent the patients in whom the tests will be used in clinical practice
2: Index test(s)	Were the index test results interpreted without knowledge of the results of the reference standard?	If a threshold was used, was it prespecified?	—	Could the conduct or interpretation of the index test have introduced bias?	Are there concerns that the index test, its conduct, or its interpretation differ from the review question?
	Yes: index test results were interpreted without knowledge of the results of the reference standard No: index test results were interpreted with knowledge of the results of the reference standard Unclear: this was not clear from the report	Yes: if the criteria for a positive test were prespecified No: if the criteria for a positive test were not prespecified Unclear: this was not clear from the report	—	Low risk: 'yes' for all signalling questions High risk: 'no' or 'unclear' for at least 1 of the 2 signalling questions	High concern: there is high concern that the conduct or interpretation of the index test differs from the way it is likely to be used in clinical practice Low concern: there is low concern that the conduct or interpretation of the index test differs from the way it is likely to be used in clinical practice
3: Target condition and reference standard(s)	Is the reference standard likely to classify the target condition correctly?	Were the reference standard results interpreted without knowledge of the results of the index tests?	—	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: histopathological examination of the entire lesion by surgical resection No: histopathological examination (irrespective of how the tissues were obtained for histopathological examination) in patients with positive test (for cancerous or precancerous lesions) and clinical follow‐up by a doctor (with or without sequential follow‐up with imaging) of all patients with negative test for a period of at least 6 months and for a maximum period of 24 months Unclear: this was not clear from the report. Such studies will be excluded Yes: reference standard results were interpreted without knowledge of the results of the index test No: reference standard results were interpreted with knowledge of the results of the index test Unclear: this was not clear from the report	—	Low risk: 'yes' for all signalling questions High risk: 'no' or 'unclear' for at least 1 of the 2 signalling questions	Low concern: histopathological examination of the entire lesion by surgical resection High concern: histopathological examination (irrespective of how the tissues were obtained for histopathological examination) in patients with positive test (for cancerous or precancerous lesions) and clinical follow‐up by a doctor (with or without sequential follow‐up with imaging) of all patients with negative test for a period of at least 6 months and for a maximum period of 24 months	—
4: Flow and timing	Was there an appropriate interval between index test and reference standard?	Did all patients receive the same reference standard?	Were all patients included in the analysis?	Could the patient flow have introduced bias?	—
	Yes: histopathological examination of the entire lesion (gold standard) ‐ performed within 2 months (chosen arbitrarily). Histopathological examination (irrespective of how the tissues were obtained for histopathological examination) in patients with positive test (for cancerous or precancerous lesions) performed within 2 months and clinical follow‐up (including sequential follow‐up with imaging) of all patients with negative test for a period of at least 6 months No: the histopathological examination was performed beyond 2 months of the index tests. The clinical follow‐up (including sequential follow‐up imaging) was performed less than 6 months after the index test, because some tumours may be slow‐growing Unclear: this was not clear from the report	Yes: histopathological examination of the entire lesion by surgical resection No: histopathological examination (irrespective of how the tissues were obtained for histopathological examination) in patients with positive test (for cancerous or precancerous lesions) and clinical follow‐up by a doctor (with or without sequential follow‐up with imaging) of all patients with negative test for a period of at least 6 months and for a maximum period of 24 months Unclear: this was not clear from the report. Such studies will be excluded	Yes: all patients meeting the selection criteria (selected participants) were included in the analysis, or data on all of the selected participants were available so that a 2 x 2 table including all selected participants could be constructed No: not all patients meeting the selection criteria were included in the analysis, or the 2 x 2 table could not be constructed using data on all selected participants Unclear: this was not clear from the report	Low risk: 'yes' for all signalling questions High risk: 'no' or 'unclear' for at least 1 signalling question	—