Nori 2004.

Study characteristics
Patient sampling	Study design: case control; appears to be case‐control type design sampling BCC and non‐BCC Data collection: retrospective image selection/prospective interpretation Period of data collection: 2 years – date range not specified Country: USA and Spain
Patient characteristics and setting	Inclusion criteria: biopsy‐confirmed BCC and convenience sample of non‐BCC with 'range of common diagnoses' (only 7 of the 69 non‐BCC had BCC on the list of possible differential diagnoses); of these 105 images were selected for clinical assessment based on superior clinical image quality. Setting: secondary (general dermatology) Division of Dermatology, Loma Linda Uni Med School; Dermatology Service, Madrid, Spain; Private care (Dermatology and Dermatologic surgery private practice); Wellmann Laboratories of Photomedicine, Massachusetts General Hospital Prior testing: NR Setting for prior testing: unspecified Exclusion criteria: none reported Sample size (participants): number included: 145 Sample size (lesions): number included: 152; 105 in VI analysis Participant characteristics: male: 98; 64% Lesion characteristics: lesion site: face/ears: 35%; trunk: 13%; limbs: extremities 45%; back 7%
Index tests	VI: no algorithm Method of diagnosis: clinical photographs Prior test data: no further information used Diagnostic threshold: NR. Lesions assigned to: high probability (BCC until confirmed otherwise), medium probability (would biopsy to rule out BCC), and low probability (no biopsy needed). Diagnosis based on: single observer (n = 2) Observer qualifications: dermatologist Experience in practice: not described Experience with index test: not described RCM: Vivascope 1000 (plus prototype device built in Wellman Laboratories (n = 20)). No algorithm; selected characteristics assessed (referenced to Gonzalez 2002) Method of diagnosis: confocal images (remote) Prior test data: no further information used; images from all 152 lesions was retrospectively analysed in a blinded fashion Diagnostic threshold: ≥ 2, 3, 4 or 5 present of 5 features selected based on prior study by same authors (elongated monomorphic basaloid nuclei; polarisation of these nuclei along the same axis of orientation; prominent inflammatory infiltrate; increased dermal vasculature; pleomorphism of the overlying epidermis indicative of actinic changes) Diagnosis based on: single observer (n = 1) Observer qualifications: 'novice confocal reviewer' reviewed all images Experience in practice: not described Experience with index test: low experience/novice users; novice confocal reviewer Other detail: the images produced by Vivascope 1000 and prototype device reportedly similar, with no measurable differences between them. Derivation aspect to study: the 5 criteria were chosen as they were "easily and unambiguously detected by non dermatopathologists and our novice reviewer so that the applicability of our results would be useful to the dermatology community as a whole."
Target condition and reference standard(s)	Type of reference standard: histological diagnosis plus other Details: 15 lesions were not biopsied (e.g. lesions like SK) because the clinical diagnosis was considered diagnostic Histology: disease positive: 83; disease negative: 54 Expert opinion: disease positive: 0; disease negative: 15 Target condition (final diagnoses): BCC: 83; 58 in VI analysis; cSCC: 4; 'benign' diagnoses: 65
Flow and timing	—
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?	No
Did the study avoid inappropriate exclusions?	Unclear
Are the included participants and chosen study setting appropriate?	No
Did the study avoid including participants with multiple lesions?	Yes
		High	High
DOMAIN 2: Index Test Reflectance confocal microscopy
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?
Was the test applied and interpreted in a clinically applicable manner?	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?	No
		Low	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
Expert opinion (with no histological confirmation) was not used as a reference standard	No
Was histology interpretation carried out by an experienced histopathologist or by a dermatopathologist?	Unclear
Were the reference standard results interpreted without knowledge of the referral diagnosis?	Unclear
		High	High
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?	No
Were all patients included in the analysis?	Unclear
Was the minimum clinical follow‐up after application of index test(s) adequate?
If more than one algorithm evaluated for the same test, was the interval between application of the different algorithms 1 month or less?
		High