PMID- 31108240
OWN - NLM
STAT- MEDLINE
DCOM- 20190625
LR  - 20190625
IS  - 1532-1967 (Electronic)
IS  - 0305-7372 (Linking)
VI  - 76
DP  - 2019 Jun
TI  - Improving attribution of adverse events in oncology clinical trials.
PG  - 33-40
LID - S0305-7372(19)30062-3 [pii]
LID - 10.1016/j.ctrv.2019.04.004 [doi]
AB  - Attribution of adverse events (AEs) is critical to oncology drug development and 
      the regulatory process. However, processes for determining the causality of AEs 
      are often sub-optimal, unreliable, and inefficient. Thus, we conducted a 
      toxicity-attribution workshop in Silver Springs MD to develop guidance for 
      improving attribution of AEs in oncology clinical trials. Attribution stakeholder 
      experts from regulatory agencies, sponsors and contract research organizations, 
      clinical trial principal investigators, pre-clinical translational scientists, 
      and research staff involved in capturing attribution information participated. We 
      also included patients treated in oncology clinical trials and academic 
      researchers with expertise in attribution. We identified numerous challenges with 
      AE attribution, including the non-informative nature of and burdens associated 
      with the 5-tier system of attribution, increased complexity of trial logistics, 
      costs and time associated with AE attribution data collection, lack of training 
      in attribution for early-career investigators, insufficient baseline assessments, 
      and lack of consistency in the reporting of treatment-related and 
      treatment-emergent AEs in publications and clinical scientific reports. We 
      developed recommendations to improve attribution: we propose transitioning from 
      the present 5-tier system to a 2-3 tier system for attribution, more complete 
      baseline information on patients' clinical status at trial entry, and mechanisms 
      for more rapid sharing of AE information during trials. Oncology societies should 
      develop recommendations and training in attribution of toxicities. We call for 
      further harmonization and synchronization of recommendations regarding causality 
      safety reporting between FDA, EMA and other regulatory agencies. Finally, we 
      suggest that journals maintain or develop standardized requirements for reporting 
      attribution in oncology clinical trials.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - George, Goldy C
AU  - George GC
AD  - The University of Texas MD Anderson Cancer Center (MD Anderson), Houston, TX, 
      United States.
FAU - Barata, Pedro C
AU  - Barata PC
AD  - Tulane University, New Orleans, LA, United States.
FAU - Campbell, Alicyn
AU  - Campbell A
AD  - Genentech, South San Francisco CA.
FAU - Chen, Alice
AU  - Chen A
AD  - National Cancer Institute (NCI), Bethesda, MD, United States.
FAU - Cortes, Jorge E
AU  - Cortes JE
AD  - MD Anderson, Houston, TX, United States.
FAU - Hyman, David M
AU  - Hyman DM
AD  - Memorial Sloan Kettering Cancer Center, New York, NY, United States.
FAU - Jones, Lee
AU  - Jones L
FAU - Karagiannis, Thomas
AU  - Karagiannis T
AD  - Genentech, Chicago, IL, United States.
FAU - Klaar, Sigrid
AU  - Klaar S
AD  - Swedish Medical Products Agency, Uppsala, Sweden.
FAU - Le-Rademacher, Jennifer G
AU  - Le-Rademacher JG
AD  - Mayo Clinic, Rochester, MN, United States.
FAU - LoRusso, Patricia
AU  - LoRusso P
AD  - Yale University Cancer Center, New Haven, CT, United States.
FAU - Mandrekar, Sumithra J
AU  - Mandrekar SJ
AD  - Mayo Clinic, Rochester, MN, United States.
FAU - Merino, Diana M
AU  - Merino DM
AD  - Friends of Cancer Research, Washington, DC, United States.
FAU - Minasian, Lori M
AU  - Minasian LM
AD  - NCI, Bethesda, MD, United States.
FAU - Mitchell, Sandra A
AU  - Mitchell SA
AD  - NCI, Rockville, MD, United States.
FAU - Montez, Sandra
AU  - Montez S
AD  - MD Anderson, Houston, TX, United States.
FAU - O'Connor, Daniel J
AU  - O'Connor DJ
AD  - Medicines and Healthcare Products Regulatory Agency, London, United Kingdom.
FAU - Pettit, Syril
AU  - Pettit S
AD  - Health and Environmental Sciences Institute, Washington DC, United States.
FAU - Silk, Elaine
AU  - Silk E
FAU - Sloan, Jeff A
AU  - Sloan JA
AD  - Mayo Clinic, Rochester, MN, United States.
FAU - Stewart, Mark
AU  - Stewart M
AD  - NCI, Bethesda, MD, United States.
FAU - Takimoto, Chris H
AU  - Takimoto CH
AD  - Forty Seven, Inc., Menlo Park, CA, United States.
FAU - Wong, Gilbert Y
AU  - Wong GY
AD  - Pfizer, New York NY, United States.
FAU - Yap, Timothy A
AU  - Yap TA
AD  - MD Anderson, Houston, TX, United States.
FAU - Cleeland, Charles S
AU  - Cleeland CS
AD  - MD Anderson, Houston, TX, United States. Electronic address: 
      ccleeland@mdanderson.org.
FAU - Hong, David S
AU  - Hong DS
AD  - MD Anderson, Houston, TX, United States. Electronic address: 
      dshong@mdanderson.org.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190425
PL  - Netherlands
TA  - Cancer Treat Rev
JT  - Cancer treatment reviews
JID - 7502030
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - *Adverse Drug Reaction Reporting Systems
MH  - Antineoplastic Agents/*adverse effects
MH  - Clinical Trials, Phase III as Topic/methods
MH  - Drug Development/methods
MH  - Humans
MH  - Randomized Controlled Trials as Topic/methods
OTO - NOTNLM
OT  - Adverse event
OT  - Attribution
OT  - Cancer treatment
OT  - Clinical trial
OT  - Symptom
OT  - Toxicity
EDAT- 2019/05/21 06:00
MHDA- 2019/06/27 06:00
CRDT- 2019/05/21 06:00
PHST- 2019/04/23 00:00 [received]
PHST- 2019/04/24 00:00 [accepted]
PHST- 2019/05/21 06:00 [pubmed]
PHST- 2019/06/27 06:00 [medline]
PHST- 2019/05/21 06:00 [entrez]
AID - S0305-7372(19)30062-3 [pii]
AID - 10.1016/j.ctrv.2019.04.004 [doi]
PST - ppublish
SO  - Cancer Treat Rev. 2019 Jun;76:33-40. doi: 10.1016/j.ctrv.2019.04.004. Epub 2019 
      Apr 25.