Tayob 2019.

Study characteristics
Patient Sampling	"The study cohort included patients with cirrhosis of any aetiology identified in the VA corporate data warehouse (CDW), a national repository of VA clinical and administrative data from a network of 153 VA hospital facilities. Patients were eligible if they had a diagnosis of cirrhosis, evidenced by the presence of International Classification of Diseases, 9th Revision (ICD‐9) codes 571.2 or 571.5, between October 1, 1996 and May 30, 2015. In addition, the analysis cohort was restricted to include (1) HCC cases with at least 1 pre‐diagnosis AFP test and (2) controls with at least 1 AFP test and a minimum of 12 months of follow‐up to confirm no HCC. For both cases and controls, we only included AFP tests with ALT and platelet laboratory tests performed within 6 months before the AFP test." Age range not reported. Males 97%
Patient characteristics and setting
Index tests	Serum AFP measurement: no specification. Predefined cut‐off value: 400 ng/mL
Target condition and reference standard(s)	"We determined HCC diagnosis in the cirrhosis cohort by using a sequential procedure. First, we identified patients with probable HCC via ICD‐9 codes, which were defined as at least 1 inpatient or 2 outpatient 155.0 codes (but without 155.1). Next, we verified these HCC diagnoses by incorporating information from the VA Central Cancer Registry (VACCR) and the VA CDW oncology raw data files."
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	"The authors disclose no 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?	No
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
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)
Were the index test results interpreted without knowledge of the results of the reference standard?
If a threshold was used, was it pre‐specified?
Could the conduct or interpretation of the index test have introduced bias?
Are there concerns that the index test, its conduct, or interpretation differ from the review question?
DOMAIN 2: Index Test (US)
Were the index test results interpreted without knowledge of the results of the reference standard?
If a threshold was used, was it pre‐specified?
Could the conduct or interpretation of the index test have introduced bias?
Are there concerns that the index test, its conduct, or interpretation differ from the review question?
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	No
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?			High
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