Estimation of knots using such "mixture regression with change point" versions is known to be computationally demanding (25), and even more so with discrete results, replicate observations, and numerous phases that span latent classes. Across site users, we use a grid search strategy using commercial software as an engine to extract Since no general purpose method scales to data of the sophistication used here and span both stages. Our method is generalizable and replicable, and it leverages two specific software packages to break the statistical model into two parts: creating random "nearby" candidate knot configurations (carried out in Matlab) and assessing different heterogeneity in resulting parameters (completed in Latent Gold). We use a combination of stochastic- and gradient-based procedures to iterate between estimating the latent class models and exploring the space of knots that are possible. (Details about the algorithm are available in SI Appendix, Section S1. .
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