Accelerated Predictive Healthcare Analytics with Pumas, A High Performance Pharmaceutical Modeling and Simulation Platform [article]

Christopher Vincent Rackauckas, Yingbo Ma, Andreas Noack, Vaibhav Dixit, Patrick Mogensen, Simon Byrne, Shubham Maddhashiya, José Bayoán Santiago Calderón, Joakim Nyberg, Joga Gobburu, Vijay Ivaturi
2020 bioRxiv   pre-print
Pharmacometric modeling establishes causal quantitative relationship between administered dose, tissue exposures, desired and undesired effects and patient's risk factors. These models are employed to de-risk drug development and guide precision medicine decisions. Recent technological advances rendered collecting real-time and detailed data easy. However, the pharmacometric tools have not been designed to handle heterogeneous, big data and complex models. The estimation methods are outdated to
more » ... solve modern healthcare challenges. We set out to design a platform that facilitates domain specific modeling and its integration with modern analytics to foster innovation and readiness to data deluge in healthcare. New specialized estimation methodologies have been developed that allow dramatic performance advances in areas that have not seen major improvements in decades. New ODE solver algorithms, such as coefficient-optimized higher order integrators and new automatic stiffness detecting algorithms which are robust to frequent discontinuities, give rise to up to 4x performance improvements across a wide range of stiff and non-stiff systems seen in pharmacometric applications. These methods combine with JIT compiler techniques and further specialize the solution process on the individual systems, allowing statically-sized optimizations and discrete sensitivity analysis via forward-mode automatic differentiation, to further enhance the accuracy and performance of the solving and parameter estimation process. We demonstrate that when all of these techniques are combined with a validated clinical trial dosing mechanism and non-compartmental analysis (NCA) suite, real applications like NLME parameter estimation see run times halved while retaining the same accuracy. Meanwhile in areas with less prior optimization of software, like optimal experimental design, we see orders of magnitude performance enhancements. Together we show a fast and modern domain specific modeling framework which lays a platform for innovation via upcoming integrations with modern analytics.
doi:10.1101/2020.11.28.402297 fatcat:th4l5p2r4nfitgwncnvuqimaua