Kanellos 2006a.

Study characteristics
Patient sampling	Country Greece Study design Prospective Setting Hospital Dates of data collection 1991 ‐ 1999 Population (n) N/R Inclusion criteria Histologically proven colorectal cancer, no detectable liver metastasis, curative surgery for colorectal cancer Exclusion criteria Confirmed liver metastasis, peritoneal carcinomatosis, ascites, emergency surgery for obstruction or perforation, smokers, obstructive biliary disease or biliary surgery, or refused consent Participants Included (n) 73
Patient characteristics and setting	Age range 64.2 (SD: 9.7) Smoking status Non‐smokers Site of primary tumour Colorectal Stage of primary tumour Stage I 14, II 37, III 22 Perioperative investigations done to ensure no residual disease Pre‐op abdominal CT, intraoperative liver palpation to exclude liver metastases Chemotherapy/radiotherapy? 22 patients with stage III cancer had adjuvant chemo Recurrences (n) 10 Site of recurrences N/R
Index tests	CEA timing 3‐monthly to 3 yrs, the 6‐monthly to 5 yrs CEA technique Monoclonal antibody technique, using a solid‐phase 2‐site mouse monoclonal antibody radioimmunoassay kit CEA threshold 5 µg/L Definition of positive 1 elevated value Which CEA value (s) used? At time of recurrence
Target condition and reference standard(s)	Follow‐up schedule Every 3 months for the first 3 years and every 6 months thereafter: clinical examination routine biochemical analysis, CXR, and CT.
Flow and timing	Timing of CEA vs reference standard (days) Simultaneous, per protocol.
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?	Unclear
Did the study avoid inappropriate exclusions?	No
		High	Low
DOMAIN 2: Index Test All CEA thresholds
If a threshold was used, was it pre‐specified?	Yes
Is the same method and instrument used for all CEA measurements?	Yes
Is there an estimation of reproducibility of the method, for example the % coefficient of variation at specific concentrations?	No
Is there an indication of method accuracy, for example, is there evidence of participation in an external quality assessment and proficiency testing scheme?	No
		Low	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?	No
		Low	Low
DOMAIN 4: Flow and Timing
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Was the index test repeated prior to the reference standard?	No
Was the the timing between index test(s) and reference standard ascertainable?	Yes
Did all patients receive a reference standard?	Yes
		Low