Blum 2004b.

Study characteristics
Patient sampling	Study design: case series Data collection: prospective; dermoscopic images assessed remotely from the patient Period of data collection: 11 November 1998‐2 March 2000 Country: Germany Test set derived: for validation of a new CAD procedure the complete collection (837 melanocytic lesions) was divided into 2 equal random subgroups n1 (training set) and n2 (test set)
Patient characteristics and setting	Inclusion criteria: melanocytic skin lesions imaged prospectively at the PLC of the Department of Dermatology, University of Tuebingen, Germany Setting: specialist unit (skin cancer/PLC) Prior testing: NR Setting for prior testing: specialist unit (skin cancer/PLC) Exclusion criteria: images from mucous membrane areas were excluded Sample size (participants): NR Sample size (lesions): number eligible: 837/number included: 837 Participant characteristics: NR Lesion characteristics: median Breslow thickness for all melanomas 0.78 mm (range 0.10‐3.50)
Index tests	Dermoscopy: 7FFM; 7PCL; ABCD; Menzies criteria Method of diagnosis: dermoscopic images Prior test data: not clearly reported; results using new CAD algorithm were, "compared with established dermoscopic classification rules applied to the same image material as the diagnostic computer algorithm." Diagnostic threshold: NR; original algorithms cited, "established dermoscopic classification rules"; authored confirmed published standard thresholds of the mentioned algorithms were used Diagnosis based on: single observer; n= 1 Observer qualifications: dermatologist Experience in practice: not described Experience with dermoscopy: not described, assumed high; "lesions were prospectively classified as benign or malignant melanocytic lesions by the principal investigator (A.B.)"
Target condition and reference standard(s)	Reference standard: histological diagnosis + follow‐up Disease‐positive: 84; disease‐negative: 185 Clinical follow‐up + histology of suspicious lesions: unexcised lesions were analysed independently by 2 of the investigators 2‐3 times in 6 months on the basis of dermoscopic criteria. These lesions were classified as benign without any suspicion of malignancy by dermoscopic criteria, and follow‐up records for at least 6 months showed no evidence of malignancy; n = 568 Target condition (final diagnoses) Melanoma (invasive): 71; melanoma (in situ): 9; lentigo maligna 4 'Benign' diagnoses: 766
Flow and timing	Excluded participants: none reported Time interval to reference test: appears consecutive; "After obtaining informed written patient consent, 269 melanocytic skin lesions were excised under local anaesthesia and the diagnosis was established by histopathology"
Comparative
Notes	‐
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Are the included patients and chosen study setting appropriate?	No
Did the study avoid including participants with multiple lesions?	Unclear
		Low	High
DOMAIN 2: Index Test Dermoscopy ‐ image‐based
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Yes
For studies reporting the accuracy of multiple diagnostic thresholds, was each threshold or algorithm interpreted without knowledge of the results of the others?	Unclear
Was the test applied and interpreted in a clinically applicable manner?	Unclear
Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	Yes
Was the test interpretation carried out by an experienced examiner?	Yes
		Low	Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Expert opinion (with no histological confirmation) was not used as a reference standard	Yes
Was histology interpretation carried out by an experienced histopathologist or by a dermatopathologist?	Unclear
		High	Unclear
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	No
Were all patients included in the analysis?	Yes
If the reference standard includes clinical follow‐up of borderline/benign appearing lesions, was there a minimum follow‐up following application of index test(s) of at least: 3 months for melanoma or cSCC or 6 months for BCC?	Yes
If more than one algorithm was evaluated for the same test, was the interval between application of the different algorithms 1 month or less?	Unclear
		High