Validation of Digital Pathology Platform for Metabolic-Associated Steatohepatitis for Clinical Trials

Aims Determine if pathologic assessment of disease activity in steatohepatitis, performed using Whole Slide Images (WSIs) on the AISight Clinical Trials platform, yields results that are comparable to those obtained from the analysis performed using glass slides. Methods and Results The accuracy of scoring for steatohepatitis (NAS ≥4 with ≥1 for each feature and absence of atypical features suggestive of other liver disease) performed on the WSI viewing platform was evaluated against scoring conducted on glass slides. Both methods were assessed for overall percent agreement (OPA) with a consensus ‘ground truth’ (GT) score, defined as the median score of a panel of 3 expert pathologists on glass slides. Each case was also read by 3 different pathologists, once on glass and once using WSIs with a minimum 2-week washout period between glass and WSI reads. It was demonstrated that the average OPA across 3 pathologists of WSI scoring with GT was non-inferior to the average OPA of glass scoring with GT (non-inferiority margin of -0.05, difference of -0.001, 95% CI of (−0.027,0.026), and p<0.0001). For each pathologist, there was a similar average OPA of WSI and glass reads with glass GT (pathologist A 0.843 and 0.849, pathologist B 0.633 and 0.605 and pathologist C 0.755 and 0.780), with intra-reader, inter-modality agreements per histologic feature being greater than published intra-reader agreements. Conclusion Accuracy of digital reads for steatohepatitis using WSIs is equivalent to glass reads in the context of a clinical trial for scoring using the Clinical Research Network scoring system. ### Competing Interest Statement Hanna Pulaski Employee of PathAI, Inc Shraddha S. Mehta Employee of PathAI, Inc Laryssa C. Manigat Former employee of PathAI, Inc Stephanie Kaufman Former employee of PathAI, Inc Hypatia Hou Employee of PathAI, Inc ILKe Nalbantoglu Contractor of PathAI, Inc Xuchen Zhang Contractor of PathAI, Inc, Emily Curl Contractor of PathAI, Inc, Ross Taliano Contractor of PathAI, Inc, Tae Hun Kim Contractor of PathAI, Inc, Michael Torbenson Contractor of PathAI, Inc, Jonathan Glickman Employee of PathAI, Inc Murray Resnick Employee of PathAI, Inc Neel Patel Employee of PathAI, Inc Cristin E. Taylor Former employee of PathAI, Inc Pierre Bedossa no conflict Michael C Montalto Employee of PathAI, Inc Andrew H Beck Employee of PathAI, Inc Katy Wack Employee of PathAI, Inc ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: WGC IRB gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors