De Placido 1998.

Study characteristics
Patient sampling	Primary objective: to verify whether sHLA‐I and sICAM‐1 serum concentrations are related to the various stages of pelvic endometriosis, which is an immune‐related disorder associated with impaired in‐vitro NK cell activity Participants: women undergoing laparoscopy for various indications Selection criteria: not reported Study design: cross‐sectional, two‐gate design, prospective collection of samples
Patient characteristics and setting	Clinical presentation: indications for surgery: endometriosis group ‐ infertility, pelvic pain, adnexal mass; controls ‐ infertility, tubal ligation, mullerian malformation; none of the subjects was affected by any systemic or pelvic disease other than endometriosis Age: mean age 25.6 years, range 22‐33 years (endometriosis group), 25.4 years, range 20‐31 (controls) Number of participants enrolled: 30 women Number of participants available for analysis: 30 women (16 in follicular, 14 in luteal cycle phase) Setting: University Hospital: Department O&G, Universita degli studi di Napoli Place of study: Naples, Italy Period of study: not stated Language: English
Index tests	Index test: sICAM‐1, sHLA‐I Details of the index test procedure as stated: serum levels of sICAM‐1 and sHLA‐I were measured by using commercial ELISA kits (CD‐54 ICAM‐1: EIA PAC, Ancell Corp, Bayport, USA and sHLA‐STAT Class I: SangStat Medical Corp, Menlo Park, USA); assay sensitivity for sICAM‐1 5 ng/l, for sHLA‐I CA‐125 3 ng/ml Threshold for positive result: not reported Examiners: no information provided; unclear if were blinded to the results of reference standard Interobserver variability: Intra‐ and interassay CVs < 12% for both assays
Target condition and reference standard(s)	Target condition: endometriosis Prevalence of target condition in the sample: n = 15/30 (50%): stage I‐II 5, stage III‐IV 10; controls n = 15 Reference standard: laparoscopy N = 30 (100%) + histology Description of positive case definition by reference standard test as reported: visualisation at surgery with subsequent histological confirmation; staging according to the rAFS classification Examiners: no information provided
Flow and timing	Time interval between index test and reference standard: blood samples were collected at surgery Withdrawals: none reported
Comparative
Key conclusions by the authors	Studies on sHLA‐I and sICAM‐1 may help to clarify the pathogenic mechanisms of endometriosis, and their serum concentrations may serve as additional markers for the early detection of recurrence of the disease during the monitoring of treatment outcome
Conflict of interest	Not reported
Notes	For sHLA‐I and sICAM‐1 there was no difference between the groups ‐ no data available for meta‐analysis
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Was a 'two‐gate' design avoided?	No
		High	High
DOMAIN 2: Index Test All tests
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?	No
Was a cycle phase considered in interpretation of the result of index test?	Yes
		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