Cho 2012.

Study characteristics
Patient sampling	Primary objectives To investigate proteins secreted in urine of women with endometriosis using proteomic techniques in order to identify potential markers for the clinical diagnosis of endometriosis; to evaluate urinary VDBP in women with endometriosis Study population Women who underwent laparoscopy for various indications including pelvic masses, pelvic pain, suspicious endometriosis, infertility and diagnostic evaluation Selection criteria Inclusion criteria: pre‐menopausal age; exclusion criteria: previous hormone or GnRH agonist use, adenomyosis, endometrial cancer, hyperplasia or endometrial polyps, infectious diseases, chronic or acute inflammatory diseases, malignancy, autoimmune disease and cardiovascular disease Study design Cross‐sectional, single‐gate design, prospective collection of samples
Patient characteristics and setting	Clinical presentation Pelvic masses, pelvic pain, suspicious endometriosis, infertility Ag: Mean age 34.22 ± 6.88 years (endometriosis group), 32.76 ± 10.26 years (control group) Number of participants enrolled 95 women Number of participants available for analysis 95 women (in follicular or luteal cycle phase, numbers not specified) Setting Gangnam Severance Hospital, Yonsei University College of Medicine Place of study Seoul, Korea Period of study January 2008 ‐ October 2010 Language English
Index tests	Index test Urinary VDBP‐Cr x serum CA‐125 Details of the index test procedure as stated Urinary VDBP was measured using specific commercial sandwich ELISA assays according to manufacturer's protocols (ALPCO Diagnostics, Salem, NH, USA); urine VDBP values were normalized to urine Cr concentrations; serum CA‐125 were measured using CA‐125 II electro chemiluminescence immunoassay with the Roche/Hitachi Modular Analytics E170 system (Roche Diagnostics, Tokyo, Japan); sample handling described Threshold for positive result Cut‐off value > 2755, not pre‐specified Examiners: No information provided; unclear if blinded to the result of reference standard Interobserver variability Not reported
Target condition and reference standard(s)	Target condition: Endometriosis Prevalence of target condition in the sample: n = 57/95 (60%): stage I‐II 5, stage III‐IV 52; controls n = 38 Reference standard: Laparoscopy and histology Description of positive case definition by reference standard as reported: Visual inspection, confirmed by histopathology; staging according to the rASRM classification Examiners: No information provided
Flow and timing	Time interval between index test and reference standard: Blood was collected preoperatively, urine was collected after induction of anaesthesia Withdrawals: None reported
Comparative
Key conclusions by the authors	Urinary VDBP levels are elevated in women with endometriosis, but they have limited value as a potential diagnostic biomarker for endometriosis (sensitivity 58%, specificity 76%)
Conflict of interest	The authors reported no conflict of interests; supported by the Basic Science Research Program of NRF of Korea by the Ministry of Education, Science and Technology (2010‐0023323)
Notes	The reported diagnostic estimates for urinary or blood test alone are presented in other reviews from this series
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Did the study avoid inappropriate exclusions?	Yes
Was a 'two‐gate' design avoided?	Yes
		Unclear	Low
DOMAIN 2: Index Test All tests
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?	No
Was a cycle phase considered in interpretation of the result of index test?	Yes
Did the study provide a clear pre‐specified definition of what was considered to be a positive result of index test?
Was the index test performed by a single operator or interpreted by consensus in a joint session?
Were the same clinical data available when the index test results were interpreted as would be available when the test is used in practice?
		High	Low
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?	Yes
		Low	Low
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?	Yes
Were all patients included in the analysis?	Yes
		Low