Szubert 2016a.

Study characteristics
Patient Sampling	Country: Poland Centres: single Study design: non‐comparative Recruitment: retrospective Method of patient selection: unclear Inappropriate exclusions: (quote) "no specific exclusion criteria"
Patient characteristics and setting	Clinical setting: unclear, probably tertiary Study entry criteria: women needing surgery for an ovarian tumour Sample size: 204 Age range: 15–84 years Mean age: not reported Median age: 46 years Percentage postmenopausal (n): 54% (66)
Index tests	Test: ADNEX Prior test: not reported Threshold for test positivity predefined: yes Threshold for test positivity: 2000 IOTA criteria 10% Type of ultrasound (TAS, TVS or both): both Operator experience of sonographer (generalist, specialist or trainee): specialist Type of technology or manufacturer of biomarker test: tumours evaluated using Aloka Alpha 10 with 3.75–7.5 MHz endovaginal probe and Aloka 3500 with a 7.5 MHz endovaginal probe (Hitach Aloka, Tokyo, Japan). A transabdominal probe was used in case of large tumours.
Target condition and reference standard(s)	Only surgical patients included Histology (n): benign 134, borderline 12, malignant 58, metastatic and others not reported
Flow and timing
Comparative	N/A
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?	Yes
A) Includes all ages regardless of menopausal status or justify restrictions	Yes
B) Includes all stages and types of ovarian cancer	Yes
C) Includes comorbidities such as infertility and endometriosis	Yes
Could the selection of patients have introduced bias?		Unclear risk
A) All patients are symptomatic or symptomatic and asymptomatic can be disaggregated
B) Prior test in primary care: self‐reported symptoms
C) Prior test secondary care: self‐reported symptoms or self‐reported symptoms plus one or more biochemical markers and ultrasound
Are there concerns that the included patients and setting do not match the review question?			Unclear
DOMAIN 2: Index Test (ADNEX)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	Yes
Were all components and thresholds of composite index test (including multivariable model) prespecified before their application?	Yes
If a composite index test was used, were components of a composite index test/model defined and assessed in a similar way (e.g. in the same healthcare setting) for all participants?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
A) Was ultrasound performed in all patients by non‐specialised sonographers
B) i. Were symptoms interpreted without the knowledge of ultrasound and biomarkers; ii: was ultrasound interpreted without the knowledge of biomarkers
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			High
DOMAIN 2: Index Test (RMI)
Were the index test results interpreted without knowledge of the results of the reference standard?
If a threshold was used, was it pre‐specified?
Were all components and thresholds of composite index test (including multivariable model) prespecified before their application?
If a composite index test was used, were components of a composite index test/model defined and assessed in a similar way (e.g. in the same healthcare setting) for all participants?
Could the conduct or interpretation of the index test have introduced bias?
A) Was ultrasound performed in all patients by non‐specialised sonographers
B) i. Were symptoms interpreted without the knowledge of ultrasound and biomarkers; ii: was ultrasound interpreted without the knowledge of biomarkers
Are there concerns that the index test, its conduct, or interpretation differ from the review question?
DOMAIN 2: Index Test (ACOG)
Were the index test results interpreted without knowledge of the results of the reference standard?
If a threshold was used, was it pre‐specified?
Were all components and thresholds of composite index test (including multivariable model) prespecified before their application?
If a composite index test was used, were components of a composite index test/model defined and assessed in a similar way (e.g. in the same healthcare setting) for all participants?
Could the conduct or interpretation of the index test have introduced bias?
A) Was ultrasound performed in all patients by non‐specialised sonographers
B) i. Were symptoms interpreted without the knowledge of ultrasound and biomarkers; ii: was ultrasound interpreted without the knowledge of biomarkers
Are there concerns that the index test, its conduct, or interpretation differ from the review question?
DOMAIN 2: Index Test (ROMA)
Were the index test results interpreted without knowledge of the results of the reference standard?
If a threshold was used, was it pre‐specified?
Were all components and thresholds of composite index test (including multivariable model) prespecified before their application?
If a composite index test was used, were components of a composite index test/model defined and assessed in a similar way (e.g. in the same healthcare setting) for all participants?
Could the conduct or interpretation of the index test have introduced bias?
A) Was ultrasound performed in all patients by non‐specialised sonographers
B) i. Were symptoms interpreted without the knowledge of ultrasound and biomarkers; ii: was ultrasound interpreted without the knowledge of biomarkers
Are there concerns that the index test, its conduct, or interpretation differ from the review question?
DOMAIN 2: Index Test (LR2)
Were the index test results interpreted without knowledge of the results of the reference standard?
If a threshold was used, was it pre‐specified?
Were all components and thresholds of composite index test (including multivariable model) prespecified before their application?
If a composite index test was used, were components of a composite index test/model defined and assessed in a similar way (e.g. in the same healthcare setting) for all participants?
Could the conduct or interpretation of the index test have introduced bias?
A) Was ultrasound performed in all patients by non‐specialised sonographers
B) i. Were symptoms interpreted without the knowledge of ultrasound and biomarkers; ii: was ultrasound interpreted without the knowledge of biomarkers
Are there concerns that the index test, its conduct, or interpretation differ from the review question?
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
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Can borderline tumours be grouped with primary ovarian cancer for the purposes of analysis?
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
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
Could the patient flow have introduced bias?		Unclear risk
DOMAIN 5: Comparative
For studies comparing two or more index tests or testing strategies in different populations, were the selection criteria for participants receiving one or other index test or testing strategy the same?
For within‐study comparisons of index tests: was the interval between application of index test less than 3 months?
For within‐study comparison of individual index tests: were index tests interpreted blind to the results of other index test results?
Could the conduct of the comparative studies have introduced bias?
Is there concern that included patients have been selected in a different way to participants in non‐comparative studies?