AI-based automation of enrollment criteria and endpoint assessment in clinical trials in liver diseases.

Journal: Nature medicine
PMID: 39112795

Abstract

Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62-0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P < 0.0001) and stage 4 (P = 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P = 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses.

Authors

  • Janani S Iyer
    PathAI Inc., Boston, Massachusetts, USA.
  • Dinkar Juyal
    PathAI, Boston, MA, USA.
  • Quang Le
    PathAI Inc., Boston, Massachusetts, USA.
  • Zahil Shanis
    PathAI, Boston, MA, USA.
  • Harsha Pokkalla
    PathAI, Boston, MA.
  • Maryam Pouryahya
    PathAI, Boston, MA, USA.
  • Aryan Pedawi
    PathAI, Boston, MA, USA.
  • S Adam Stanford-Moore
    PathAI, Boston, MA, USA.
  • Charles Biddle-Snead
    PathAI, Boston, MA, USA.
  • Oscar Carrasco-Zevallos
    PathAI, Boston, MA.
  • Mary Lin
    PathAI, Boston, MA, USA.
  • Robert Egger
    PathAI, Boston, Massachusetts.
  • Sara Hoffman
    PathAI, Boston, MA, USA.
  • Hunter Elliott
    PathAI, Boston, MA.
  • Kenneth Leidal
    PathAI, Boston, MA, USA.
  • Robert P Myers
    Gilead Sciences, Inc., Foster City, CA.
  • Chuhan Chung
    Gilead Sciences, Inc., Foster City, CA.
  • Andrew N Billin
    Gilead Sciences, Inc., Foster City, CA, USA.
  • Timothy R Watkins
    Gilead Sciences, Inc., Foster City, CA, USA.
  • Scott D Patterson
    Gilead Sciences, Inc., Foster City, CA, USA.
  • Murray Resnick
    PathAI, Boston, MA.
  • Katy Wack
    PathAI, Boston, MA, USA.
  • Jon Glickman
    PathAI, Boston, MA, USA.
  • Alastair D Burt
    Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Rohit Loomba
    From the Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering (A.H., W.D.O.), and Department of Food Science and Human Nutrition (J.W.E.), University of Illinois at Urbana-Champaign, 306 N Wright St, Urbana, IL 61801; Department of Radiology (M.B., M.P.A.), Liver Imaging Group, Department of Radiology (E.H., C.B.S.), and NAFLD Research Center, Division of Gastroenterology, Department of Medicine (R.L.), University of California, San Diego, La Jolla, Calif; and Department of Ultrasound, Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland (M.B.).
  • Arun J Sanyal
    Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
  • Ben Glass
    PathAI, Boston, MA, USA.
  • Michael C Montalto
    PathAI, Boston, MA.
  • Amaro Taylor-Weiner
    Cancer Program, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge.
  • Ilan Wapinski
    PathAI, Boston, MA.
  • Andrew H Beck

Keywords

External Resources

Popular Topics
Recent Journals