Enhancing Preclinical Rigor: Evaluating Robustness and Numerical Stability in a Chronic Pancreatitis Mouse Model

Chronic pancreatitis (CP) is characterized by progressive fibrosis, inflammation, and pancreatic atrophy. Here, we evaluate a milder CP model using only 42 cerulein injections administered in both male and female C57BL/6J (BL6) and BALB/c mice. We further assess the therapeutic potential of the RORγt inhibitor GSK805. We employed a multi-tiered analytical approach, including the robustness of conclusion (RC), unit fragility index, and robustness index, to evaluate consistency and numerical stability of conclusions. The model reliably produced key hallmarks of CP: reduced pancreas-to-body weight ratio, elevated collagen I deposition, and tubular complex formation with an RC of 100%. In contrast, the induction of Tnf, Ifng, Il10, Il23r, Il6, and Il1b expression was less robust and partially strain specific. Il23r and Il10 were significantly induced during CP in female and male BL6 but not in BALB/c mice. Il6 was significantly induced in female and male BALB/c but only reached significance in BL6 when sexes were combined. Treatment with GSK805 reduced Il23r expression level significantly in BL6 mice, but no reliable improvements in other disease characteristics were observed. Overall, this study validates a simplified, robust CP model and advocates for the integration of complementary statistical metrics to strengthen the reliability of scientific conclusion.