Choi 2019.
| Study characteristics | |||
| Patient Sampling | This was a phase 3 biomarker study based on the EDRN definition. Serum samples were collected from four previous prospective studies conducted by our group (Fig. 1): one EDRN biomarker phase 4 HCC surveillance study for cirrhosis (the PRIUS study, clinicaltrials.gov, registration no. NCT 01446666, 407 patients) and three randomised controlled trials (RCTs) to explore the optimal antiviral treatment regimen in patients with chronic hepatitis B (CHB; NCT01639066, 102 patients; NCT01639092, 90 patients; and NCT01023217, 90 patients). Age range not reported. Males 69% | ||
| Patient characteristics and setting | |||
| Index tests | AFP was measured using a chemiluminescent microparticle immunoassay (ARCHITECT i2000SR; Abbott, Chicago, IL). All clinical data, including the presence of HCC, were blinded to laboratory technicians to avoid measurement bias. Diagnosis of HCC was triggered only by suspicious nodule on surveillance images (US, CT, and/or MRI). Biomarkers were not involved in the decision making. US: no specification US + AFP: at least one positive, no other specification |
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| Target condition and reference standard(s) | Confirmation of HCC was based on the predefined criteria by study protocols, i.e. results of histologic examination and/or typical imaging features (nodule > 1 cm with arterial hypervascularity and portal/delayed‐phase washout) by CT and/or MR. | ||
| Flow and timing | No information on interval between index test and reference standard | ||
| Comparative | |||
| Notes | Supported by grants from the Korean Gastroenterology Fund for Future Development; the Korean National Health Clinical Research project, Ministry of Health & Welfare, Republic of Korea (HC15C3380); the Korean Health Technology R&D Project, Ministry of Health & Welfare (HI17C1862); the National Research Foundation of Korea (NECA‐S‐17‐008); and the Technology Innovation Program (10079271) funded by
the Ministry of Trade, Industry & Energy of the Republic of Korea. Potential conflict of interest: Dr. Lim consults, advises, is on the speakers bureau for, and receives grants from Bayer Healthcare and Gilead Sciences. |
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| 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? | 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) | |||
| 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) | |||
| 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 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? | No | ||
| Were all patients included in the analysis? | Yes | ||
| Could the patient flow have introduced bias? | Low risk | ||