Overriding a model

Patients from an in silico clinical trial share the same computational model (CM). They differ from each other through CM overrides, i.e. modifications of some CM constructs.

What can be overriden in a model

Constructs that can be overriden in a CM are:

• parameters: the value of any parameter can be overriden
• variables: the initial condition of any variable can be overriden
• compartments: the volume of any compartment can be overriden

What can be used to override a model

The above can be overriden with either:

• a Protocol
• a Virtual Population

Protocol overrides

A [Protocol] can override a CM construct with either a plain numerical value or with a formula (i.e. can depend on the values of other constructs)

Virtual Population overrides

Virtual Population overrides correspond to the values taken by patient-specific descriptors. Contrary to a Protocol, a Virtual Population can only override CM constructs with numerical values

Order of precedence

In case of conflicts, Protocol overrides always take precedence over Virtual Population overrides:

1. If no protocol or Virtual Population overrides a construct, the value it takes is the one defined in the CM.
2. If a Virtual Population overrides a construct, it will vary across the population, meaning each patient will be assigned with a different value
3. If a Protocol overrides a construct, the protocol override takes precedence over any existing Virtual Population override. Therefore the construct will be take a different value for each protocol arm but will be constant across the population in a given arm.