Table 1.

Quantitative Systems Pharmacology Model example use questions with most likely domain of interest within the pharmaceutical research and development (R&D) process

QSPM Use Questions	Where in R&D
What is the relative therapeutic potential of several competing compounds?	Research/Biology
What amount of pathway modulation is needed (aka do we need 90% coverage?)?	Research
What is the impact of pharmacologically inhibiting target “x” by “y”%	Research
In treating this disease, what combination of targets will optimize response?	Research
Which biomarker, of those that can be measured, is most indicative of hitting the target?	Research
What experiments should be done to understand the mechanism better and guide target selection (hypothesis generation)?	Research
Did the trial design (sampling scheme) allow observation of important changes (safety, efficacy)?	Research/Clinical
What clinical trial population should be studied to understand the mechanism better and guide target or dose selection (hypothesis generation)?	Research/Clinical
How reasonable are the current mechanism-of-action assumptions (impact of being wrong)?	Research/Clinical
What don't we understand about how this drug works?	Research/Clinical
What is the impact of treating with mono-therapy versus adding on to standard of care?	Clinical
What is the optimal/most efficient sampling scheme for biomarkers/clinical measures we have not previously sampled but are outputs of the QSPM?	Clinical
Is there a pharmacologic combination that would increase the therapeutic window of the candidate drug?	Clinical
What happens if a patient stops taking the drug?	Clinical
How can we answer PKPD and biomarker questions for long t1/2 drugs, where clinical studies are not practical?	Clinical
Is the proposed dose/regimen optimized (or what range of doses should be investigated)?	POC onwards
Should compound(s) be progressed/entered to new indication?	Clinical lifespan