PMID- 33616650
OWN - NLM
STAT- MEDLINE
DCOM- 20220224
LR  - 20220531
IS  - 1460-2105 (Electronic)
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 113
IP  - 8
DP  - 2021 Aug 2
TI  - Underreporting of Symptomatic Adverse Events in Phase I Clinical Trials.
PG  - 980-988
LID - 10.1093/jnci/djab015 [doi]
AB  - BACKGROUND: Clinician reporting of symptomatic adverse events (AEs) in phase I 
      trials uses the Common Terminology Criteria for Adverse Events (CTCAE). The 
      utility of the patient-reported outcomes (PROs) version of the CTCAE (PRO-CTCAE) 
      in this setting is unknown. This prospective, observational study compared 
      patient- and clinician-reported symptomatic AEs in phase I patients. METHODS: 
      Phase I study-eligible patients at Princess Margaret were surveyed with the 
      PRO-CTCAE full-item library (78 symptomatic AEs) at baseline (BL), mid-cycle 1, 
      and mid-cycle 2 (C2). Patient and trial characteristics, best response, and 
      survival data were collected. Presence or absence of patient- (PRO-CTCAE) or 
      clinician-reported symptomatic AEs were compared (kappa) at defined timepoints 
      and overall (BL+ mid-cycle 1 + C2). RESULTS: Of 292 patients approached from May 
      2017 to January 2019, a total of 265 (90.8%) were consented, with 243 (91.7%) 
      evaluable and 552 PRO-CTCAE surveys (completion rate = 98.7%) included in 
      analyses. Evaluation of overall patient-reported symptomatic AEs identified 50 
      PRO-CTCAE and 11 CTCAE items with 10% or greater reporting frequency. Nineteen 
      CTCAE items were reported as 1% or less despite matched PRO-CTCAE items reporting 
      as 10% or greater. Underreported categories included sexual health, bodily 
      emissions, and cognition. Clinician- relative to patient-reporting frequency 
      (ratio) demonstrated 9 symptomatic AEs with a 50-fold or more lower clinician 
      reporting rate. Overall patient-clinician agreement for individual symptomatic 
      AEs ranged from poor (kappa = 0.00-0.19) to moderate (kappa = 0.40-0.59), with 
      discordance driven by lack of clinician reporting. Dyspnea (kappa = 0.54) and 
      peripheral neuropathy (kappa = 0.63) at BL and limb edema (kappa = 0.55) at C2 
      demonstrated the highest patient-clinician agreement. CONCLUSIONS: Poor to 
      moderate patient-clinician agreement for symptomatic AEs suggests clinician 
      underreporting in phase I trials. Analyses of severity and interference PRO 
      categories are ongoing.
CI  - (c) The Author(s) 2021. Published by Oxford University Press. All rights reserved. 
      For permissions, please email: journals.permissions@oup.com.
FAU - Veitch, Zachary W
AU  - Veitch ZW
AUID- ORCID: 0000-0002-3223-5045
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
FAU - Shepshelovich, Daniel
AU  - Shepshelovich D
AUID- ORCID: 0000-0002-9145-618X
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
AD  - Department of Internal Medicine, Sackler School of Medicine, Tel-Aviv Sourasky 
      Medical Center, Tel-Aviv, Israel.
FAU - Gallagher, Christina
AU  - Gallagher C
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
FAU - Wang, Lisa
AU  - Wang L
AD  - Department of Biostatistics, University of Toronto, Toronto, ON, Canada.
FAU - Abdul Razak, Albiruni R
AU  - Abdul Razak AR
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
FAU - Spreafico, Anna
AU  - Spreafico A
AUID- ORCID: 0000-0002-3034-3042
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
FAU - Bedard, Philippe L
AU  - Bedard PL
AUID- ORCID: 0000-0002-6771-2999
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
FAU - Siu, Lillian L
AU  - Siu LL
AUID- ORCID: 0000-0002-3500-0540
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
FAU - Minasian, Lori
AU  - Minasian L
AUID- ORCID: 0000-0002-0472-4079
AD  - Division of Cancer Prevention, National Cancer Institute, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Hansen, Aaron R
AU  - Hansen AR
AUID- ORCID: 0000-0002-2363-8707
AD  - Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (Antineoplastic Agents)
SB  - IM
CIN - doi: 10.1093/jnci/djab017
MH  - *Antineoplastic Agents/adverse effects
MH  - Clinical Trials, Phase I as Topic
MH  - Cognition
MH  - Humans
MH  - *Neoplasms/drug therapy
MH  - *Patient Reported Outcome Measures
MH  - Prospective Studies
MH  - Surveys and Questionnaires
PMC - PMC8502480
EDAT- 2021/02/23 06:00
MHDA- 2022/02/25 06:00
PMCR- 2021/02/22
CRDT- 2021/02/22 12:14
PHST- 2020/07/31 00:00 [received]
PHST- 2020/11/04 00:00 [revised]
PHST- 2021/01/04 00:00 [accepted]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2022/02/25 06:00 [medline]
PHST- 2021/02/22 12:14 [entrez]
PHST- 2021/02/22 00:00 [pmc-release]
AID - 6146406 [pii]
AID - djab015 [pii]
AID - 10.1093/jnci/djab015 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 2021 Aug 2;113(8):980-988. doi: 10.1093/jnci/djab015.