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?

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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.

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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?

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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.

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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?

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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.

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