Terstappen 2013.

Study characteristics
Patient sampling	Study design: Case series Data collection: NR Period of data collection: NR Country: Sweden
Patient characteristics and setting	Inclusion criteria: Lesions clinically suspicious for melanoma and showing positive SIAscopic findings Setting: Secondary (general dermatology) (details from authors' institution) Prior testing: Clinical suspicion of malignancy without dermatoscopic suspicion, showing positive SIAscopic findings Setting for prior testing: Secondary (general dermatology) Exclusion criteria: Poor‐quality index test image: 9 lesions excluded due to technical problems Sample size (participants): N eligible: 69; N included: 60 Sample size (lesions): N eligible: 69; N included: 60 Participant characteristics: ≤ 1 mm thickness: 17/29 melanomas; 8/29 melanomas Breslow thickness < 0.76 mm (Clark II ‐ III) and 9/29 Breslow thickness 0.76 − ≤ 1.0 mm (Clark II ‐ III) and 12 lesions Breslow thickness ≥ 1.1 (Clark III ‐ V)
Index tests	Computer‐assisted diagnosis ‐ Spectroscopy‐based MSI‐CAD system: SIAscope (Astron Clinica, UK) (classifier NR) System details: Spectrophotometric imaging system with hand–held skin probe (SIAscope V) and integrated software (Dermetrics Version 2.0, Astron Clinica Ltd., Great Britain) No derivation aspect (external validation study) Lesion characteristics assessed: Dermal melanin, blood displacement, collagen holes, erythematous blush Additional predictors included: No further information used Method of diagnosis: In‐person spectroscopic images (SIAgraphs) CAD‐based diagnosis Prior/other test data: None reported CAD output: The instrument generates 4 images depicting the concentration of haemoglobin, melanin, collagen and dermal melanin Diagnostic threshold: "SIAscopic findings indicating melanoma were applied using the method described by Moncrieff (2002)" Results described for: "the combined features (presence of blood displacement with erythematous blush, collagen holes and presence of dermal melanin)". NB Moncrieff 2002 is a derivation study for SIAscope and suggests a number of combinations of features indicative of melanoma, the same features investigated here
Target condition and reference standard(s)	Reference standard: Histological diagnosis alone The excised specimens were routinely processed and the histological sections, 4 μm thick, were stained with haematoxylin and eosin. Before cutting the specimen in slices, the lesion was oriented and the positions of the SIAscopic areas of interest were outlined by comparisons with the overview clinical photo of the lesion N participants/lesions: 60 Disease‐positive: 29; Disease‐negative: 31 Target condition (Final diagnoses) Melanoma: invasive 29, in situ 13 (included as D‐) BCC: 2 Benign diagnoses: 2 sebhorrheic keratosis; 4 melanocytic lesions; 10 dysplastic naevi
Flow and timing	Exclusions from analysis: 9/69 lesions (2 invasive melanoma, 2 melanoma in situ, and 5 benign lesions) had to be excluded due to technical problems Time interval to reference test: NR
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?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Are the included patients and chosen study setting appropriate?	No
Did the study avoid including participants with multiple lesions?	Unclear
Was an adequate spectrum of cases used to train the algorithm?
		Unclear	High
DOMAIN 2: Index Test Computer‐assisted diagnosis
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?	No
Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	Yes
Was the test interpretation carried out by an experienced examiner?	Unclear
Was the CAD model evaluated in an independent study population?	Yes
Was model overfitting accounted for during model development?
Was the diagnostic threshold to determine presence or absence of disease established in a previously published study?	No
		High	High
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	No
Was the use of expert opinion (with no histological confirmation) avoided as the reference standard?	Yes
Was histology interpretation carried out by an experienced histopathologist or by a dermatopathologist?	Unclear
Were the reference standard results likely to correctly classify the target condition (disease negative)?	Yes
		High	Unclear
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	No
		High