PMID- 33930159
OWN - NLM
STAT- MEDLINE
DCOM- 20220224
LR  - 20220531
IS  - 1460-2105 (Electronic)
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 114
IP  - 1
DP  - 2022 Jan 11
TI  - Patient-Reported Outcomes in Pediatric Cancer Registration Trials: A US Food and 
      Drug Administration Perspective.
PG  - 12-19
LID - 10.1093/jnci/djab087 [doi]
AB  - Pediatric patient-reported outcome (PRO) data can help inform the US Food and 
      Drug Administration's (FDA's) benefit-risk assessment of cancer therapeutics by 
      quantifying symptom and functional outcomes from the patient's perspective. This 
      study assessed use of PROs in commercial pediatric oncology trials submitted to 
      the FDA for regulatory review. FDA databases were searched to identify pediatric 
      oncology product applications approved between 1997 and 2020. Sponsor-submitted 
      documents were reviewed to determine whether PRO data were collected, which 
      instruments were used, and the quality of collected data (ie, sample size, 
      completion rates, and use of fit-for-purpose instruments). The role of PROs in 
      each trial (endpoint hierarchy) was also recorded in addition to whether any PRO 
      endpoints were included in product labeling. We reviewed 17 pediatric oncology 
      applications, 4 of which included PRO data: denosumab, tisagenlecleucel, 
      larotrectinib, and selumetinib. In these 4 instances, PROs served as exploratory 
      endpoints and were not incorporated in product labeling. Trials that collected 
      PRO data were phase II or phase I/II single-arm studies with sample sizes of 28 
      to 88 patients. Symptomatic adverse events (AEs) were characterized using 
      clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) without 
      additional patient self-report. PROs were infrequently used in pediatric cancer 
      registration trials. When PROs were used, PRO data were limited by lack of a 
      clear research objective and corresponding prospective statistical analysis plan. 
      Contemporary PRO symptom libraries, such as the National Cancer Institute's 
      Pediatric PRO-CTCAE, may provide an opportunity to better evaluate the occurrence 
      and impact of symptomatic AEs, from the patient's perspective, in pediatric 
      oncology trials.
CI  - Published by Oxford University Press 2021. This work is written by US Government 
      employees and is in the public domain in the US.
FAU - Murugappan, Meena N
AU  - Murugappan MN
AUID- ORCID: 0000-0001-7865-3931
AD  - Office of Oncologic Diseases, Center for Drug Evaluation and Research, US Food 
      and Drug Administration, Silver Spring, MD, USA.
FAU - King-Kallimanis, Bellinda L
AU  - King-Kallimanis BL
AUID- ORCID: 0000-0001-9418-9374
AD  - Oncology Center for Excellence, US Food and Drug Administration, Silver Spring, 
      MD, USA.
FAU - Reaman, Gregory H
AU  - Reaman GH
AD  - Oncology Center for Excellence, US Food and Drug Administration, Silver Spring, 
      MD, USA.
FAU - Bhatnagar, Vishal
AU  - Bhatnagar V
AD  - Oncology Center for Excellence, US Food and Drug Administration, Silver Spring, 
      MD, USA.
FAU - Horodniceanu, Erica G
AU  - Horodniceanu EG
AD  - Oncology Center for Excellence, US Food and Drug Administration, Silver Spring, 
      MD, USA.
FAU - Bouchkouj, Najat
AU  - Bouchkouj N
AD  - Oncology Center for Excellence, US Food and Drug Administration, Silver Spring, 
      MD, USA.
FAU - Kluetz, Paul G
AU  - Kluetz PG
AD  - Oncology Center for Excellence, US Food and Drug Administration, Silver Spring, 
      MD, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - *Antineoplastic Agents/adverse effects
MH  - Child
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase II as Topic
MH  - Humans
MH  - *Neoplasms/epidemiology
MH  - Patient Reported Outcome Measures
MH  - Prospective Studies
MH  - United States/epidemiology
MH  - United States Food and Drug Administration
PMC - PMC8755487
EDAT- 2021/05/01 06:00
MHDA- 2022/02/25 06:00
PMCR- 2021/04/30
CRDT- 2021/04/30 17:44
PHST- 2021/01/28 00:00 [received]
PHST- 2021/04/10 00:00 [revised]
PHST- 2021/04/20 00:00 [accepted]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2022/02/25 06:00 [medline]
PHST- 2021/04/30 17:44 [entrez]
PHST- 2021/04/30 00:00 [pmc-release]
AID - 6261320 [pii]
AID - djab087 [pii]
AID - 10.1093/jnci/djab087 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 2022 Jan 11;114(1):12-19. doi: 10.1093/jnci/djab087.