Figure 6
Between-model comparisons of distress after pooling the experimental subgroups. (A) The distress of the carbon tetrachloride (CCl4), pancreatitis (Panc), pancreatic cancer (PDA), and the cholestasis (BDL) model was evaluated using the RELSAmax values, with the reference built from data of laboratory A (transmitter implantation model, measured variables: body weight, burrowing activity as well as the distress score, the red line denotes the maximally experienced severity in the telemetry experiment). A Kruskal–Wallis test shows significant differences between the RELSAmax estimates of the animal models in panel (A) (χ2 = 54.86, df = 3, p < 0.0001). Differences were observed between CCl4 and PDA (**padj < 0.01), CCl4 and BDL (****padj < 0.0001), pancreatitis and BDL (***padj < 0.001) as well as between PDA and BDL (****padj < 0.0001). The following order of model severity can be seen by ordering the RELSAmax estimates: \({\widehat{\text{R}}}_{{\text{CCl}}_{4}}\) = 0.40, CI95% [0.29; 0.52]) < PDA (\({\widehat{\text{R}}}_{\text{PDA}}\) = 0.61, CI95% [0.50; 0.71]) < Pancreatitis (\({\widehat{\text{R}}}_{\text{Panc}}\) = 0.70, CI95% [0.56; 0.83]) < BDL (\({\widehat{\text{R}}}_{\text{BDL}}\) = 1.10, CI95% [1.00; 1.20]). (B) Testing the robustness of the procedure by implementing a different reference set from laboratory B with the variables body weight and burrowing activity. The treatment groups also showed significant differences using the Kruskal–Wallis test (χ2 = 53.15, df = 3, p < 0.0001). Pairwise differences were observed between CCl4 and PDA (***padj < 0.001), CCl4 and Pancreatitis (****padj < 0.0001), CCl4 and BDL (****padj < 0.0001), Pancreatitis and BDL (**padj < 0.01) as well as between PDA and BDL (****padj < 0.0001). Here, the order of RELSAmax estimates showed as follows: \({\widehat{\text{R}}}_{{\text{CCl}}_{4}}\) = 0.31, CI95% [0.22; 0.40]) < PDA (\({\widehat{\text{R}}}_{\text{PDA}}\) = 0.58, CI95% [0.50; 0.67]) < Pancreatitis (\({\widehat{\text{R}}}_{\text{Panc}}\) = 0.65, CI95% [0.54; 0.76]) < BDL (\({\widehat{\text{R}}}_{\text{BDL}}\)= 0.89, CI95% [0.81; 0.96]). The graphs depict the RELSAmax values obtained from individual RELSA analyses (pooled subgroups for each animal model) and the bootstrapped median estimator together with the 95% confidence intervals. Data of vehicle and drug-treated groups were pooled. (A,B) CCl4 n = 22, PDA n = 26, Pancreatitis n = 16, BDL n = 30.
