| Signalling question | Signalling question | Signalling question | Risk of bias | Applicability |
| Domain 1: participant selection |
| Participant selection | Was a consecutive or random sample of participants enrolled? | Was a case‐control design avoided? | Did a study avoid inappropriate exclusions? | Could the selection of participants have introduced bias? | Are there concerns that the included participants and setting do not match the review question? |
| Yes: all consecutive participants or random sample of participants with suspected primary biliary cholangitis. No: only selected participants were enrolled. Unclear: this was not clear from the report. | Yes: a case‐control design was avoided. No: a case‐control design was not avoided. Unclear: this was not clear from the report. | Yes: a study avoided inappropriate exclusions, e.g. it included asymptomatic people with elevated ALP or people with elevated ALP and other autoimmune diseases. No: a study excluded difficult‐to‐diagnose participants, e.g. participants with suspected primary biliary cholangitis with other autoimmune disease were excluded. Unclear: this was not clear from the report. | Low risk: 'yes' for all signalling questions. High/unclear risk: 'no' or 'unclear' for at least 1 signalling question. | Low: the selected participants and settings matched the review question. High: the selected participants and settings differed from the review question. Unclear: this was not clear from the report. |
| Domain 2: index test |
| Index test | Were the index test results interpreted without knowledge of the results of the reference standard? | If a threshold was used, was it prespecified? | ‐ | Could the conduct or interpretation of the index test have introduced bias? | Are there concerns that the index test, its conduct, or its interpretation differ from the review question? |
| Yes: index test was always conducted and interpreted before the liver biopsy. No: index test was interpreted with knowledge of results of liver biopsy. Unclear: this was not clear from the report. | Yes: a threshold was prespecified for all autoantibodies. No: a threshold was not prespecified for all autoantibodies. Unclear: this was not clear from the report. | ‐ | Low risk: 'yes' for all signalling questions. High/unclear risk: 'no' or 'unclear' for at least 1 signalling question. | Low: there are low concerns the index test conduct or interpretation differed from the review question. High: there are high concerns the index test methodology or interpretation varied from the review question. Unclear: this was not clear from the report. |
| Domain 3: reference standard |
| Reference standard | Is the reference standard likely to classify the target condition correctly? | Were the reference standard results, interpreted without knowledge of the results of the index test? | ‐ | Could the reference standard, its conduct, or its interpretation have introduced bias? | Are there concerns that the target condition as defined by the reference standard does not match the review question? |
| Low: all participants were verified by liver biopsy and histology. No: some included participants were not verified by liver biopsy and histology, and this was related to the result of the index test, i.e. participants who were AMA positive. Unclear: this was not clear from the report. | Yes: the liver biopsy results were interpreted without knowledge of index test results. No: the liver biopsy results were interpreted with knowledge of index test results. Unclear: this was not clear from the report. | ‐ | Low risk: 'yes' for all signalling questions. High/unclear risk: 'no' or 'unclear' for at least 1 signalling question. | Low: all participants underwent common techniques of liver biopsy and their histology reports were classified as compatible with primary biliary cholangitis or not. High: all participants or a proportion of them did not undergo common or generally accepted liver biopsy procedures or histology techniques used were not in line with accepted standard. |
| Domain 4: flow and timing |
| Flow and Timing | Was there an appropriate interval between index tests and the reference standard? | Did all participants receive the reference standard? | Were all participants included in the analysis? | Could the participants flow have introduced bias? | ‐ |
| Yes: the interval between index tests and the reference standard was ≤ 6 months (an arbitrary value). No: the interval between index tests and the reference standard was > 6 months. Unclear: this was not clear from the report. | Low risk: all participants received the reference standard, i.e. liver biopsy and histology. High risk: some included participants received reference standard but it was inconclusive for primary biliary cholangitis or some participants did not receive the reference standard due to AMA positivity. Unclear: this was not clear from the report. | Yes: all participants recruited into the study were included in the analysis. No: the number of participants included in the analysis differed from the number of participants enrolled in the study. Unclear: this was not clear from the report. | Low risk: 'yes' for all signalling questions. High/unclear risk: 'no' or 'unclear' for at least 1 signalling question. | ‐ |
