Glud 2009.

Study characteristics
Patient sampling	Study design: Case series Data collection: Prospective Period of data collection: January to April 2007 Country: Denmark
Patient characteristics and setting	Inclusion criteria: Patients referred for excision biopsy of pigmented lesions where the diagnosis of melanoma could not be excluded on clinical investigation Setting: Secondary (other); Dept Plastic Surgery and Burn Unit Prior testing: Clinical suspicion of malignancy without dermatoscopic suspicion Setting for prior testing: Secondary (not further specified); Department of Plastic Surgery and Burn Unit Exclusion criteria: None reported Sample size (participants): N included: 65 Sample size (lesions): N included: 83 Participant characteristics: Median age 47 years (18 ‐ 90); Male ‐ 29 (45%) Lesion characteristics: Melanoma thickness 0.29 mm to 2.18 mm
Index tests	Dermoscopy: No algorithm Method of diagnosis: Dermoscopic images Prior test data: No further information used Diagnostic threshold: NR "dermoscopic images were examined by an experienced dermatologist" Diagnosis based on: Single observer (n = 1) Observer qualifications: Dermatologist Experience in practice: High experience or ‘Expert’ Experience with index test: High experience/‘Expert’ users The dermoscopic and SIAgraphic images were obtained by SIAscope II (Amon Clinica, Cambridge, UK) and stored using the proprietary Dermetrics software (Astron Clinica) Computer‐assisted diagnosis ‐ Spectroscopy‐based MSI‐CAD system: SIAscope II (Astron Clinica, UK )(classifier NR) System details: Skin lesion is interrogated with light of different wavelengths and the reflection spectra are analyzed by proprietary algorithms showing distribution, position and quantity of melanin, blood, and collagen within the papillary dermis (the SIAgraphs) No derivation aspect (external validation) Derivation described in prior study – See Moncrieff 2002; Govindan 2007 Lesion characteristics assessed: Analysis of dermal melanin, erythem­atous blush, lesion asymmetry, collagen 'holes', blood commas, or irregularities in the collagen Additional predictors included: None Method of diagnosis: Spectroscopic images, SIAgraphic images CAD‐based diagnosis Prior/other test data: Unclear CAD output: Binary (based on Australian Scoring System): ‘strong chance of melanoma' or 'low risk of melanoma' Diagnostic threshold: Australian Scoring System; Threshold not reported
Target condition and reference standard(s)	Reference standard Histological diagnosis alone (excision biopsy) Breslow thickness and Clark level were determined by standard histopathologic examination. Tumour staging was performed as described by Balch 2001 according to the 2001 melanoma staging system Disease‐positive: 12; Disease‐negative: 71 Target condition (Final diagnoses) Melanoma (invasive): 7; Melanoma (in situ): 5; 1 melanoma metastasis (incl as benign) Sebhorrheic keratosis: 1; Benign naevus: 57; 'Benign' diagnoses: Bowens 1; haemangioma 1; lentigo simplex 2; epidermal naevi 2; DF 6
Flow and timing	Participant excluded from analysis: None reported Interval between tests: NR Interval to reference standard: Images taken prior to biopsy
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?	No
Was an adequate spectrum of cases used to train the algorithm?
		Low	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?	Yes
Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	Yes
Was the test interpretation carried out by an experienced examiner?
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?	Yes
		Low	Low
DOMAIN 2: Index Test Dermoscopy
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?	Unclear
Were thresholds or criteria for diagnosis reported in sufficient detail to allow replication?	No
Was the test interpretation carried out by an experienced examiner?	Yes
Was the CAD model evaluated in an independent study population?
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?
		Unclear	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?	Unclear
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?	Yes
Were the reference standard results likely to correctly classify the target condition (disease negative)?	Yes
		Unclear	Low
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?	Yes
		Unclear