Table 6.
Updated Banff recommendations on best practice for pathology and molecular endpoints in clinical trials.
| A. Banff recommendations for use of the Banff classification in clinical trials |
| • The primary effort should focus on applying the most recent Banff classification in clinical trials |
| • Exact criteria used for inclusion in the trial, highlighting any deviations from the current official Banff Classification, should be clearly outlined in the study protocol and reporting |
| • The inclusion of biopsy-based transcript diagnostics, or not, in clinical trials should be stated in the trial protocol and in the reporting |
| • Open reporting of and public access to the granular study data (including individual Banff Lesions Scores) to allow for retrospective reassessment of study results is recommended |
| B. Banff recommendations on best practices for pathology endpoints in clinical trials |
| • Pathologists to participate in the design and choice of endpoints |
| • Panel of (central) pathologists (3 optimal to avoid a tie) |
| • Sufficient clinical information to (central) pathologists for correct diagnosis, including detailed information on DSA status for AMR diagnosis |
| • Adjudication mechanism (how discordance between pathologists is addressed) |
| • Whole slide digital images for centralized slide review |
| • Auditable assessments (scoring that can be reviewed and audited externally) |
| • Granular scoring and reporting of all Banff lesions, not only final Banff Diagnostic Category (consider using detailed phenotyping and lesion scoring for secondary endpoints) |
| • Quantitate changes (use of continuous scores and percentages rather than semiquantitative scoring) |
| • Centralized processing of ancillary testing, eg, immunohistochemistry (C4d; immunoglobulins and complement) and electron microscopy |
| C. Banff recommendations on best practices for molecular endpoints in clinical trials |
| • Molecular evaluation of kidney transplant biopsies can be considered for clinical trials, if available |
| • Large reference data sets should be well-annotated |
| • High reproducibility/replication of assays is required before use in clinical trials |
| • Pathogenesis-based transcript strategy appears useful and can be completed by classifier approaches (no single gene test is specific) |
| • Centralized testing advantageous for multicenter trials |
| • Proper methodological approaches are needed (for assay performance, data analysis, ...). This adds statistical power, potentially reducing sample size and costs |
| • Quality assurance is mandatory (interlaboratory, interplatform, and interassay reproducibility; development of standardized positive and negative controls and quantitative diagnostic reference standard) |