Walter 2012.

Study characteristics
Patient sampling	Study design: RCT (control group only included) Data collection: prospective Period of data collection: March 2008‐May 2010 Country: UK
Patient characteristics and setting	Inclusion criteria: adults with any suspicious PSL, i.e. any lesion presented by a patient, or opportunistically seen by a family doctor or practice nurse, that could not immediately be diagnosed as benign and about which the patient could not be reassured. Setting: primary. 15 general practices in eastern England Prior testing: clinical suspicion of malignancy without dermatoscopic suspicion Setting for prior testing: primary Exclusion criteria: those unable to give informed consent or considered inappropriate to include by their family doctor Sample size (participants): number eligible: 1297; number included: 1293 Sample size (lesions): number eligible: 1580; number included: 1583 Participant characteristics: mean age: 44.6 years (SD 16.8). Male: 465 (36%). Ethnicity: white 1214 (93.9%); mixed 45 (3.5%); missing: 34 (2.6%) Lesion characteristics: lesion thickness ≤ 1 mm: in 'more than half' of MM
Index tests	VI: Glasgow/MacKie revised 7‐point checklist (MacKie 1990) Method of diagnosis: in‐person diagnosis Prior test data: N/A Diagnostic threshold: NR Diagnosis based on: single observer (n = 30) Observer qualifications: 28 GPs and 2 nurse practitioners recruited as 'lead clinicians' (2 per practice); appears as though they conducted all skin examinations. Excluded GPs with known dermatological expertise, e.g. current hospital practitioners, clinical assistants in dermatology, and GPs with a special interest in dermatology Experience in practice: mixed GP experience, median of 15 years' experience (range 4‐27 years); assumed low experience with PSLs. 7 had undergone some training in dermatology: 3 had a short dermatology training post, 3 were on clinical attachment to an out‐patient clinic, and 1 was unspecified
Target condition and reference standard(s)	Reference standard: histological diagnosis plus follow‐up and expert opinion Histology (not further described) 215 (histology result missing in further 4) Disease positive: 35; disease negative: 180 Clinical follow‐up plus histology of suspicious lesions: 22 of the 411 referred patients were monitored (not further described); 566 of the 1162 not referred underwent expert review and were then re‐assessed at 3‐6 months Disease positive: 1; disease negative: 588 Expert opinion. Reviewed by 2 dermatology experts using the recorded clinical history and examination, a digital photograph, and MoleMate image where available Disease positive: 0; disease negative: 725 Target condition (final diagnoses) Melanoma (invasive): 30; melanoma (in situ): 6; BCC: 10 'Benign' diagnoses: 1306
Flow and timing	Excluded participants: 417 withdrew from control group after randomisation. 10 did not attend for dermatology assessment; 19 excluded; 1 died; 4 missing histology (in referred group; included as benign?); plus 12 with unknown outcome (in non‐referred group, assumed benign and included) Time interval to reference test: suspicious lesions referred under 2‐week wait system
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?	Yes
Did the study avoid including participants with multiple lesions?	No
		Low	High
DOMAIN 2: Index Test Visual Inspection ‐ in‐person
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?	No
		Low	High
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?	No
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
		High	High
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?	No
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?
		High