Study Endpoints
For efficacy endpoints, trials in 30 WRs used a response rate, a binary
endpoint, as the primary endpoint. This includes trials in 25 WRs used
overall response rate (ORR) assessed by investigators, 2 used overall
response rate assessed by independent review committees (IRC), 5 used a
complete response (CR) rate assessed by investigators and 1 used a
complete response rate assessed by an IRC. Some trials have both ORR and
CR rates evaluations. Pediatric trials in 5 WRs used the time to event
as efficacy endpoint, with 2 using event-free survival (EFS), 1
progression-free survival (PFS) assessed by investigators, and 2 used
progression-free survival (PFS) assessed by an IRC.
Within one WR, typically a dose-escalation/dose-determination
phase/study is required to evaluate the PK, safety, and preliminary
activity of the drug to establish the MTD and/or RP2D in pediatric
patients. For programs where the extrapolation from adult efficacy was
feasible, the dose-finding phase/study was to identify the optimal safe
and tolerable dose in pediatrics that achieves similar exposures to
those achieved in adults. Other studies require different primary
endpoints: 18 pediatric trials included PK/PD endpoints, 14 pediatric
trials used safety related primary endpoint and 11 used other primary
endpoints include clinical activity such as a change from baseline or
other unspecified efficacy or activity endpoints.
Commonly used secondary endpoints include response rate, time to event
endpoints, PK/PD endpoints, safety endpoints, and many other endpoints
such as palatability and electrocardiogram measures.