Alexander 1978.

Study characteristics
Patient Sampling	Patients who attended the Liver Clinic at Groote Schuur Hospital (South Africa) over the 2‐year period 1975 ‐ 1976: 35 HCC; 8 chronic hepatitis B; 12 chronic active hepatitis; 43 alcoholic cirrhosis Age range and % of males not reported
Patient characteristics and setting
Index tests	AFP was measured by radio‐immunoassay as described by Purves and Purves; the assay is sensitive in the nanogram range and the upper limit of normal is 30 ng/mL.
Target condition and reference standard(s)	The clinical diagnosis of hepatoma was always supported by arteriography, liver scanning and histological examination. Alcoholic cirrhosis was diagnosed if the history indicated prolonged alcohol abuse, and if clinical evidence of cirrhosis and portal hypertension was found on examination. Histological confirmation was obtained when the prothrombin index and platelet count permitted biopsy. The 'diagnosis of chronic active hepatitis was confirmed histologically in every case.
Flow and timing	No information on interval between index test and reference standard
Comparative
Notes	No information on conflicts of interest or funding
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Unclear
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?	Unclear
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?	No
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?		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