Antivirals Detail
News and Resources
Related Products
Our Modeling and Simulation Approach in Antivirals
Our modeling and simulation approach in antivirals, as in other therapeutic domains, is to integrate relevant sub-models (e.g., PK, PD, viral dynamics, trial outcomes, adherence), estimate key parameters from trial data, and simulate candidate trial designs. Key parameters describe patient adherence or compliance to the prescribed regimen, compartmental pharmacokinetics, viral inhibition (in-vivo IC50), virus and immune cell characteristics (depending on the patient population), and trial characteristics such as dropout rates. The disease model can be complex but typically includes at a minimum uninfected cells, actively infected cells, latently infected cells, and multiple viral strains. Differential equations describe the virus-cell interaction over time, including resistance development.
Project deliverables in an HIV or HCV engagement might include:
- Design of the next trial or sequence of trials including doses, arm sizes, and patient enrollment criteria, to minimize key uncertainties or maximize the probability of meeting endpoint criteria
- Go/no-go decision recommendations
- In early phases and in preclinical research, extrapolation from in vitro, animal, and healthy volunteer data to patients, capturing uncertainties
- In later phases, refined choices of target population, regimen, and formulation, for example, finding the net effect of trading off higher adherence to a once-a-day regimen with its less favorable pharmacokinetic profile relative to twice-a-day dosing.