Pellacani 2014a (cons).

Study characteristics
Patient sampling	Study design: case series (consultation group documented here) Data collection: prospective Period of data collection: January 2010 to December 2010 Country: Italy
Patient characteristics and setting	Inclusion criteria: people requesting a mole check or with suspicion of melanoma who were referred to PLC and who were then found to have atypical lesions on dermoscopy. Those in whom diagnosis could not be determined on dermoscopy were referred for an 'outcome decision' (consultation group). Participants were referred on the basis of both urgent access (melanoma suspected in a single lesion by GP or other dermatologist) and scheduled access (referred for dermoscopy and total body examination). Setting: specialist unit (skin cancer/pigmented lesions clinic) Prior testing: dermatoscopic suspicion in all cases. All participants underwent dermoscopy in the PLC; those with dermoscopically atypical lesions were referred for RCM, either to document a lesion already selected for excision (documentation group, reported in Pellacani 2014b (doc)) or for an 'outcome decision' (consultation group), i.e. diagnosis could not be determined on dermoscopy. Setting for prior testing: specialist unit (skin cancer/pigmented lesions clinic) Exclusion criteria: clinically or dermatoscopically clear‐cut epithelial tumours, or both, were not enrolled; poor‐quality index test image. In 9 cases, RCM could not be performed (5 RCM documentation and 4 RCM consultation) due to the presence of artefacts, hyperkeratosis, or ulcerations, impeding imaging. Sample size (participants): number eligible: 1005 examined with dermoscopy; number included: 252 referred for RCM consultation Sample size (lesions): number eligible: NR; number included: 308 for RCM documentation Participant characteristics: median age 41.7 years (IQR 31.9 to 52.1 years); for all 1005 referred participants: 443 male (44%); consultation group only: history of melanoma/skin cancer 23 (7%); family history of melanoma 30 (10%). Fitzpatrick phototype I to II: 150 (49%); Type III to IV 116 (38%) Lesion characteristics: lesion site (full sample) head/neck: 9%; trunk: 59%; upper limbs/shoulder: 12%; lower limbs/hip: 20%
Index tests	RCM: RCM score. Vivascope 1500 Method of diagnosis: in person Prior test data: participants were "referred to confocal unit;" confocal reader was blinded to the participant pathway and aware that lesions were dermoscopically atypical for 'RCM documentation' or for 'RCM consultation.' Diagnostic threshold: NR, Pellacani 2005 cited Diagnosis based on: single observer (n = 1) Observer qualifications: dermatologist (assumed; participants were "referred to confocal unit") Experience in practice: not described Experience with index test: not described but 'confocal unit' described Other detail: dermatoscopy examinations were conducted using the Dermlite HR (3Gen LLC, San Juan Capistrano, CA, USA). Lesions that were scheduled for digital monitoring were also acquired by means of FotoFinder (TeachScreen GmbH, Bad Birnbach, Germany) using 20‐fold magnification.
Target condition and reference standard(s)	Type of reference standard: histological diagnosis plus FU and cancer registry FU Histology (not further described): 81 (consultation group); overall dataset – 292 excised (see Pellacani 2014b (doc)) Clinical FU: 227. 28 of which were subsequently excised because of observed dermatoscopic changes (all benign). Most non‐excised lesions (178/199 (89.4%)) were followed up for 1 year; the others were lost at the 1‐year FU. Cancer registry FU: those lost to clinical FU were checked on the tumour registry; no melanomas were diagnosed in participants scheduled for FU after baseline examinations. Target condition (final diagnoses): melanoma (invasive): 13; melanoma (in situ): 9; BCC: 19; 1 melanoma metastasis; Clark naevus 71; Spitz nevus 5; solar lentigo, SK or lichen planus‐like keratosis 0; other benign 207 (8 with histological diagnosis (25 Clark naevi, 2 Spitz naevi and 1 benign non‐melanocytic lesion) and 199 benign on FU)
Flow and timing	Excluded participants: 9 excluded due to RCM failure
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?	No
Are the included participants and chosen study setting appropriate?	Unclear
Did the study avoid including participants with multiple lesions?	No
		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?	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?	Yes
		Low	Low
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
Were the reference standard results interpreted without knowledge of the referral diagnosis?	Unclear
		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?	No
Were all patients included in the analysis?	No
Was the minimum clinical follow‐up after application of index test(s) adequate?	Yes
If more than one algorithm evaluated for the same test, was the interval between application of the different algorithms 1 month or less?
		High