  When the early stopping parameter n.earlystop is relatively small or the
cohortsize value is not optimized via simulation, it may be better to use p.tox
< 1.4 * target.DLT.rate, or try out different cohort sizes, or increase
n.earlystop, whichever is both feasible and provides better operating
characteristics. This is because if the cohortsize was not optimized via
simulation, even when n.earlystop = 12, the BOIN escalation/de-escalation rules
generated using p.tox = 1.4 * target.DLT.rate could be exactly the same as
those calculated using p.tox > 3 * target.DLT.rate, which might not be
acceptable for some pediatric trials targeting 10% DLT rate. The traditional
3+3 design stops the dose finding process when 3 patients have been treated at
the current dose level, 0 DLT has been observed, and the next higher dose has
already been eliminated. If additional 3 patients were required to be treated
at the current dose in the situation described above, the corresponding
boundary table could be generated using BOIN design with target DLT rates
ranging from 18% to 29%, p.saf ranging from 8% to 26%, and p.tox ranging from
39% to 99%. To generate the boundary table of this 3+3 design variant, BOIN
parameters also need to satisfy a set of conditions.
