Barillari 1992.

Study characteristics
Patient sampling	Country Italy Study design Prospective Setting Hospital Dates of data collection N/R Population (n) 66 Inclusion criteria Rectal cancer treated for cure Exclusion criteria N/R Participants included (n) 66
Patient characteristics and setting	Age range 62.3 yrs (mean) Smoking status N/R Site of primary tumour rectum Stage of primary tumour 6 Stage A, 32 Stage B, 28 Stage C Perioperative investigations done to ensure no residual disease N/R Chemotherapy/radiotherapy? N/R Recurrences (n) 33 Site of recurrences Local 10, Metastatic 25 (Lungs 3, peritoneum 10,bones 2,liver 21, multiple 8)
Index tests	CEA timing 3‐monthly CEA CEA technique CEA was analysed using a direct radioimmunologic method (CEA‐PR; Sorin Biomedica) CEA threshold 3 µg/L Definition of positive Any elevation of 1 of the antigen levels greater than the limit defined by the between assay coefficient of variation (calculated on the basis of 2 standard deviations) was defined as significant, and the assay was repeated after 10 days. Which CEA value (s) used? Repeated value.
Target condition and reference standard(s)	Follow‐up schedule 3‐monthly to 60 months: blood CEA, TPA, CA19.9 and clinical exam. 6, 18, 30, 42, 54 months: USS Abdomen, CXR, Barium Enema. 12, 24, 36, 48, 60 months: colonoscopy, CT body. 6, 18, 30, 42 months: Bone scan. Reference standard Abdominal or total body CT, a chest x‐ray examination, a bone scan, an endoscopy, and a clinical examination were performed. An exploratory laparotomy was performed when all three markers were elevated, even if recurrence was not confirmed by total body CT scan and clinical examinations
Flow and timing	Timing of CEA vs reference standard (days) 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?	Yes
Did the study avoid inappropriate exclusions?	Yes
		Low	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?	No
Were all patients included in the analysis?	Yes
Was the index test repeated prior to the reference standard?	Yes
Was the the timing between index test(s) and reference standard ascertainable?	Unclear
Did all patients receive a reference standard?	Yes
		Low