PMID- 20479400
OWN - NLM
STAT- MEDLINE
DCOM- 20100706
LR  - 20220408
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 28
IP  - 18
DP  - 2010 Jun 20
TI  - Evaluation of the value of attribution in the interpretation of adverse event 
      data: a North Central Cancer Treatment Group and American College of Surgeons 
      Oncology Group investigation.
PG  - 3002-7
LID - 10.1200/JCO.2009.27.4282 [doi]
AB  - PURPOSE: In March 1998, Common Toxicity Criteria (CTC) version 2.0 introduced the 
      collection of attribution of adverse events (AEs) to study drug. We investigate 
      whether attribution adds value to the interpretation of AE data. PATIENTS AND 
      METHODS: Patients in the placebo arm of two phase III trials-North Central Cancer 
      Treatment Group Trial 97-24-51 (carboxyamino-triazole v placebo in advanced 
      non-small-cell lung cancer) and American College of Surgeons Oncology Group Trial 
      Z9001 (imatinib mesylate v placebo after resection of primary gastrointestinal 
      stromal tumors)-were studied. Attribution was categorized as unrelated (not 
      related or unlikely) and related (possible, probable, or definite). RESULTS: In 
      total, 398 patients (84 from Trial 97-24-51 and 314 from Trial Z9001) and 7,736 
      AEs were included; 47% and 50% of the placebo-arm AEs, respectively, were 
      reported as related. When the same AE was reported in the same patient on 
      multiple visits, the attribution category changed at least once 36% and 31% of 
      the time. AE type and sex (Trial Z9001) and AE type and performance status (Trial 
      97-24-51) were associated with a higher likelihood of AEs being deemed related. 
      CONCLUSION: Nearly 50% of AEs were reported as attributed to study drug on the 
      placebo arm of two randomized clinical trials. These data provide strong evidence 
      that AE attribution is difficult to determine, unreliable, and of questionable 
      value in interpreting AE data in randomized clinical trials.
FAU - Hillman, Shauna L
AU  - Hillman SL
AD  - Mayo Clinic, Rochester, MN 55905, USA. hillman.shauna@mayo.edu
FAU - Mandrekar, Sumithra J
AU  - Mandrekar SJ
FAU - Bot, Brian
AU  - Bot B
FAU - DeMatteo, Ronald P
AU  - DeMatteo RP
FAU - Perez, Edith A
AU  - Perez EA
FAU - Ballman, Karla V
AU  - Ballman KV
FAU - Nelson, Heidi
AU  - Nelson H
FAU - Buckner, Jan C
AU  - Buckner JC
FAU - Sargent, Daniel J
AU  - Sargent DJ
LA  - eng
GR  - U10 CA025224/CA/NCI NIH HHS/United States
GR  - U10 CA076001/CA/NCI NIH HHS/United States
GR  - CA-25224/CA/NCI NIH HHS/United States
GR  - CA-076001/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100517
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Placebos)
RN  - 0 (Pyrimidines)
RN  - 0 (Triazoles)
RN  - 6ST3ZF52WB (carboxyamido-triazole)
RN  - 8A1O1M485B (Imatinib Mesylate)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Adverse Drug Reaction Reporting Systems/*statistics & numerical data
MH  - Aged
MH  - Aged, 80 and over
MH  - Benzamides
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Clinical Trials, Phase III as Topic
MH  - Double-Blind Method
MH  - Female
MH  - Gastrointestinal Stromal Tumors/*drug therapy/pathology
MH  - Humans
MH  - Imatinib Mesylate
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Piperazines/*therapeutic use
MH  - Placebos
MH  - Pyrimidines/*therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Retrospective Studies
MH  - Survival Rate
MH  - Treatment Outcome
MH  - Triazoles/*therapeutic use
MH  - Young Adult
PMC - PMC2903334
COIS- Authors' disclosures of potential conflicts of interest and author contributions 
      are found at the end of this article.
EDAT- 2010/05/19 06:00
MHDA- 2010/07/07 06:00
PMCR- 2011/06/20
CRDT- 2010/05/19 06:00
PHST- 2010/05/19 06:00 [entrez]
PHST- 2010/05/19 06:00 [pubmed]
PHST- 2010/07/07 06:00 [medline]
PHST- 2011/06/20 00:00 [pmc-release]
AID - JCO.2009.27.4282 [pii]
AID - 74282 [pii]
AID - 10.1200/JCO.2009.27.4282 [doi]
PST - ppublish
SO  - J Clin Oncol. 2010 Jun 20;28(18):3002-7. doi: 10.1200/JCO.2009.27.4282. Epub 2010 
      May 17.