What are some examples of successful mathematical attempts in clinical setting, specifically at the patient-disease-drug level?
To clarify, by patient-disease-drug level, I mean the mathematical work is approved to be used as part of a decision making process to prescribe a specific treatment for a specific patient?
I do not mean general modeling attempts that study and simulate on a more or less theoretical level.
Additionally, are these mathematical work have to be approved by the regulators like the FDA or a national board of physicians?
Best Answer
An example of a simple mathematical/evolutionary game theory model used to determine treatment scheduling in clinical treatment of metastic and castrate resistant prostate cancer can be found at https://www.nature.com/articles/s41467-017-01968-5. While the clinical trial is on-going, initial results show that the model derived treatment schedule offers significant improvement in time to treatment failure when compared to the standard-of-care.
In short, the authors use a 3 population evolutionary game theory model to study the interplay between androgen dependent, androgen independent and androgen producing cancerous cells. They use this model to determine an "adaptive therapy" dosing strategy for abiraterone, a drug that strongly effects androgen dependent cancer cells.Typically, prostate cancer cells develop resistance to abiraterone. Consequently, disease progression and treatment failure is observed in roughly a year (11 months for Prostate Specific Antigen [a biomarker] increase and 16 months for radiographic progression). While small, the study shows that the median time to PSA and radiographic progression is at least 27 months when patients follow the model derived treatment schedule.
Adaptive therapy is designed to take advantage of the "cost of resistance." When abiraterone concentrations are high, it is hypothesized that the relative cost of resistance is lower than the fitness benefit, so cancerous cells are likely to evolve into abiraterone resistant strains. Adaptive therapy aims to use treatment holidays to protect against the development of these resistant strains. In general, treatment is suspended when PSA reaches half of pre-treatment levels, and only restarts once pre-treatment PSA levels have been reached.