Generalizations of the 'Linear Chain Trick': incorporating more flexible dwell time distributions into mean field ODE models

In this paper we generalize the Linear Chain Trick (LCT; aka the Gamma Chain Trick) to help provide modelers more flexibility to incorporate appropriate dwell time assumptions into mean field ODEs, and help clarify connections between individual-level stochastic model assumptions and the structure of corresponding mean field ODEs. The LCT is a technique used to construct mean field ODE models from continuous-time stochastic state transition models where the time an individual spends in a given state (i.e., the dwell time) is Erlang distributed (i.e., gamma distributed with integer shape parameter). Despite the LCT's widespread use, we lack general theory to facilitate the easy application of this technique, especially for complex models. Modelers must therefore choose between constructing ODE models using heuristics with oversimplified dwell time assumptions, using time consuming derivations from first principles, or to instead use non-ODE models (like integro-differential or delay differential equations) which can be cumbersome to derive and analyze. Here, we provide analytical results that enable modelers to more efficiently construct ODE models using the LCT or related extensions. Specifically, we provide (1) novel LCT extensions for various scenarios found in applications, including conditional dwell time distributions; (2) formulations of these LCT extensions that bypass the need to derive ODEs from integral equations; and (3) a novel Generalized Linear Chain Trick (GLCT) framework that extends the LCT to a much broader set of possible dwell time distribution assumptions, including the flexible phase-type distributions which can approximate distributions on R+ and can be fit to data.