Tong 2001.

Study characteristics
Patient Sampling	"From 1991 to 1998, 602 patients who were referred to the Liver Center at the Huntington Memorial Hospital in Pasadena, California, USA were enrolled in the surveillance for HCC. All patients were positive for either hepatitis C virus antibodies (anti‐HCV; Ortho HCV EIA; Ortho Diagnostics, Raritan, NJ, USA), or for hepatitis B virus surface antibodies. To be included, all patients had to have at least 1 year of follow‐up in our clinic (Liver Center)." Age range not reported. Males 59%
Patient characteristics and setting
Index tests	"AFP levels were measured at two commercial laboratories. One laboratory at Huntington Memorial Hospital in Pasadena, California used the Axsym EIA (Abbott Laboratories; the upper limit of normal was 10.9 ng/mL. The second laboratory, Nichols Laboratories in Los Angeles, California, used an in‐house chemoluminescent method from 1990 to 1995 (the upper limit of normal was 18 ng/mL). For serum samples sent to Nichols Laboratories after 1995, the ACS‐180 chemoluminescent test (Chiron Diagnostics, Emeryville, CA, USA) was used (the upper limit of normal was 8.1 ng/mL.For final data presentation, ratios were reconverted to AFP values by multiplication of the AFP ratio by the upper limit of normal of the currently available test (8.1 ng/mL)."
Target condition and reference standard(s)	US, CT, and histology
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	No information on funding or conflicts of interest
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		Low risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (AFP)
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?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 2: Index Test (US+AFP)
DOMAIN 2: Index Test (US)
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
Could the reference standard, its conduct, or its interpretation have introduced bias?		High risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	No
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		High risk