Johnson 1978.

Study characteristics
Patient Sampling	50 patients with histologically‐confirmed primary hepatocellular carcinoma were investigated at diagnosis. Age range: 53‐74. % of males not reported
Patient characteristics and setting	30 patients, all men, aged 53‐74 years, had developed the tumour on the basis of underlying cirrhosis. In the other 20 cases (11 men and 9 women, aged 27‐72 years), the tumour had arisen in an otherwise normal liver.
Index tests	Quote: "AFP concentrations were estimated using a sensitive radioimmunoassay technique capable of detecting concentrations of 2 IU/ml (2‐1 ng/mL). In contrast, positive results with the immunodiffusion technique may be obtained only at concentrations above about 5000 IU/mL (5250 ng/mL). All samples were run in duplicate, and in those in which the concentration was above normal (as established from 50 healthy controls from the unit staff) the assay was repeated at least once."
Target condition and reference standard(s)	50 patients with histologically‐confirmed primary hepatocellular carcinoma were investigated at diagnosis.
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	No conflicts of interest declared
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?	No
Did the study avoid inappropriate exclusions?	Yes
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?			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?	No
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?	Yes
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low 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?	Yes
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Low risk