The Continual Reassessment Method (CRM)
was published in 1990.
It is the most frequently used
model-based design in oncology.
The assignment of doses
is very similar to the up-and-down designs,
in the sense that we can escalate,
deescalate or repeat the dose
for the next cohort of patients.
Patients can be assigned
one at a time or in groups.
We need to specify the total sample size.
It's usually 18-24,
if we have maybe four dose levels or five.
The dose assignment for the next cohort
or the next patient is determined based
on a parsimonious model.
It is also referred to as the working model.
In the initial escalation,
sometimes this working model
tells us to assign high doses right away.
However, because of ethical constraints,
we do not skip doses
in the initial escalation.
at the lowest dose level
and then it goes to dose level
2, 3, and 4, etc...