Ohtsuka 2008.

Study characteristics
Patient sampling	Country Japan Study design Retrospective Setting Hospital Dates of data collection 2002 ‐ 2005 Population (n) 138 Inclusion criteria Curative resection, stage 0 – III according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum, and Anus, 7th edition, 2006, no residuals Exclusion criteria History of another malignancy before or after the operation, lost to follow‐up Participants Included (n) 97
Patient characteristics and setting	Age range 70 (37 ‐ 86) Smoking status Chronic benign disease or smoking in 46 cases Site of primary tumour 32 right colon, 32 left colon, 30 rectum, 3 multiple Stage of primary tumour 0 in 8, I in 12, II in 37, and III in 40 Perioperative investigations done to ensure no residual disease N/R Chemotherapy/radiotherapy? Yes, but not described Recurrences (n) 22 Site of recurrences
Index tests	CEA timing Every 1 – 3 months during the initial 6 months after the operation, every 3 – 6 months from 6 months to 2 years, and every 6 – 12 months during 2 – 5 years after the operation CEA technique CEA, a latex immunoassay, Mitsubishi Chemical Ltd., Japan CEA threshold 5 µg/L Definition of positive N/R Which CEA value (s) used? N/R
Target condition and reference standard(s)	Follow‐up schedule the follow‐up schedule of the tumour markers and physical examination after the operation were: every 1 – 3 months during the initial 6 months after the operation, every 3 – 6 months from 6 months to 2 years, and every 6 – 12 months during 2 – 5 years after the operation. Radiological examinations including abdominal ultrasonography, computed tomography (CT), chest X‐ray, gastrointestinal series, and/or endoscopic evaluation were performed every 6 – 12 months during the follow‐up period. Marker evaluations and physical/radiological examinations were performed at shorter‐term intervals than those described above in patients with suspected recurrence, those undergoing chemotherapy, or in those demonstrating marker elevations. Reference standard radiological examinations / histology
Flow and timing	Timing of CEA vs reference standard (days) per protocol or reference standard triggered by rise in CEA
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?	Unclear
Did all patients receive a reference standard?	Yes
		Low