Gopal 2014.

Study characteristics
Patient Sampling	This study was reported as a retrospective case‐control study of cirrhotic patients with and without HCC. They included all patients diagnosed with HCC at Parkland Hospital between January 2005 and June 2012. Patients were identified by a combination of International Classification of Diseases, 9th revision, codes for HCC (155.0 or 155.2), a prospectively maintained list of patients seen in a multidisciplinary liver tumour clinic, and tumour conference presentation lists. In the HCC group, they excluded patients who did not have an AFP level before HCC diagnosis, and in the control group (patients with cirrhosis), they excluded patients with any suspicious liver mass on imaging and those who did not have an AFP test during the study period (January 2010–July 2011). Age range: 49‐61. Males 71%
Patient characteristics and setting
Index tests	AFP. Quote: "We dichotomized AFP at a cut‐off value of 20 ng/mL because this is the most commonly reported and used cut‐off value in clinical practice."
Target condition and reference standard(s)	HCC: Quote: "Two authors (A.G.S. andA.C.Y.) adjudicated all HCC cases to confirm that they met diagnostic criteria, based on AASLD guidelines". Cirrhosis: "Patients initially were identified using a previously validated combination of International Classification of Diseases, 9th revision, codes. Patients were required to have at least 6 months of follow‐up evaluation to confirm the absence of HCC."
Flow and timing	No data on interval between index test and reference standard. Quote: "Between January 2005 and June 2012, there were 457 patients with cirrhosis who were diagnosed with HCC. We excluded 5 patients who did not have an AFP level before HCC diagnosis. Between January 2010 and July 2011, there were 914 patients with cirrhosis who were seen in an outpatient setting at Parkland Hospital, of whom 238 patients were excluded for a lack of AFP level or insufficient follow‐up duration."
Comparative
Notes	Conflicts of interest: the authors disclosed no conflicts.
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	No
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?	No
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		High 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?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear 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?	Unclear
Were all patients included in the analysis?	No
Could the patient flow have introduced bias?		High risk