PMID- 36843283
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20231114
IS  - 1520-5711 (Electronic)
IS  - 1054-3406 (Linking)
VI  - 33
IP  - 6
DP  - 2023 Nov 2
TI  - Extent of safety database in pediatric drug development: types of assessment, 
      analytical precision, and pathway for extrapolation through on-target effects.
PG  - 770-785
LID - 10.1080/10543406.2023.2172425 [doi]
AB  - Pediatric patients should have access to medicines that have been appropriately 
      evaluated for safety and efficacy through revised labelling. Given this goal, the 
      adequacy of the pediatric clinical development plan and resulting safety database 
      are critical factors to inform a favorable benefit-risk assessment for the 
      intended use of the medicinal product. While extrapolation from adults can be 
      used to support efficacy of drugs in children, there may be a reluctance to use 
      the same approach in safety assessments, wiping out potential gains in trial 
      efficiency through a reduction of sample size. To address this issue, we explore 
      safety review in pediatric trials, including specific types of safety assessments 
      and precision on the estimation of event rates for specific adverse events (AEs) 
      that can be achieved. In addition, we discuss the assessments which can provide a 
      benchmark for the use of extrapolation of safety that focuses on on-target 
      effects. Finally, we explore a unified approach for understanding precision using 
      Bayesian approaches as the most appropriate methodology to describe or ascertain 
      risk in probabilistic terms for the estimate of the event rate of specific AEs.
FAU - Gamalo, Margaret
AU  - Gamalo M
AUID- ORCID: 0000-0003-2428-3298
AD  - Pfizer, Collegeville, PA, USA.
FAU - Zhao, Yihua
AU  - Zhao Y
AD  - Flatiron Health, New York, NY, USA.
FAU - Gao, Aijun
AU  - Gao A
AD  - Alexion Pharmaceuticals, Boston, MA, USA.
FAU - Ye, Jingjing
AU  - Ye J
AUID- ORCID: 0000-0003-0086-2228
AD  - BeiGene, Cambridge, MA, USA.
FAU - Lin, Junjing
AU  - Lin J
AUID- ORCID: 0000-0002-7448-2984
AD  - Takeda Pharmaceuticals, Cambridge, MA, USA.
FAU - Eshida, Eiji
AU  - Eshida E
AD  - Sunovion, Great Falls, VA, USA.
FAU - Choi, YounJeong
AU  - Choi Y
AD  - Roche/Genentech, San Francisco, CA, USA.
FAU - Nelson, Robert
AU  - Nelson R
AD  - Johnson & Johnson, Spring House, PA, USA.
LA  - eng
PT  - Journal Article
DEP - 20230226
PL  - England
TA  - J Biopharm Stat
JT  - Journal of biopharmaceutical statistics
JID - 9200436
SB  - IM
MH  - Adult
MH  - Humans
MH  - Child
MH  - *Bayes Theorem
MH  - Sample Size
MH  - Databases, Factual
MH  - Risk Assessment
OTO - NOTNLM
OT  - Adverse drug reactions
OT  - Bayesian methods
OT  - confidence level
OT  - hypothesis testing
OT  - on-target effects
EDAT- 2023/02/28 06:00
MHDA- 2023/11/02 12:45
CRDT- 2023/02/27 01:13
PHST- 2023/11/02 12:45 [medline]
PHST- 2023/02/28 06:00 [pubmed]
PHST- 2023/02/27 01:13 [entrez]
AID - 10.1080/10543406.2023.2172425 [doi]
PST - ppublish
SO  - J Biopharm Stat. 2023 Nov 2;33(6):770-785. doi: 10.1080/10543406.2023.2172425. 
      Epub 2023 Feb 26.