scholarly journals 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

2010 ◽  
Vol 28 (18) ◽  
pp. 3002-3007 ◽  
Author(s):  
Shauna L. Hillman ◽  
Sumithra J. Mandrekar ◽  
Brian Bot ◽  
Ronald P. DeMatteo ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Group ◽  
Cancer Treatment ◽  
Randomized Clinical Trials ◽  
Study Drug ◽  
Phase Iii ◽  
Oncology Group ◽  
North Central ◽  
American College Of Surgeons ◽  
Group Trial

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.

Dealing With a Deluge of Data: An Assessment of Adverse Event Data on North Central Cancer Treatment Group Trials

2005 ◽  
Vol 23 (36) ◽  
pp. 9275-9281 ◽  
Author(s):  
Michelle R. Mahoney ◽  
Daniel J. Sargent ◽  
Michael J. O'Connell ◽  
Richard M. Goldberg ◽  
Paul Schaefer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Patient Safety ◽  
Treatment Group ◽  
Cancer Treatment ◽  
Phase Iii ◽  
Small Subset ◽  
North Central ◽  
Normal Limits ◽  
Life Threatening

Purpose Adverse events (AEs) are monitored in clinical trials for patient safety, to satisfy reporting requirements, and develop safety profiles. Recently, much attention has been placed on the reporting of serious AEs (SAEs) that are either life threatening or lethal in clinical trials. However, SAEs comprise a small subset of all AE data collected for trials; the majority of AE data collected are routine AEs (RAEs) regarding non–life-threatening events. We assessed the utility of the RAE data collected, relative to the volume. Patients and Methods We surveyed the RAE data from 26 North Central Cancer Treatment Group coordinated trials. Results A total of 8,318 (11%) of 75,598 of RAEs required queries. Of these, 86% were protocol-required RAEs, 83% of RAEs required per protocol were within normal limits (eg, platelets) or not present, and 61% of extra AEs were mild. One fifth of RAEs were considered unlikely to be related or unrelated to treatment. Overall, 3% of events were severe, life threatening, or caused death. Only 1% of RAE data reported required expedited reporting (eg, via Adverse Event Expedited Reporting System). Results indicate that 72% of RAEs would be eliminated if only the maximum severity per patient and type were required. These results were validated in a large phase III trial. Conclusion The majority of RAEs identified, transcribed, and entered are not clinically important. Our data suggest that reducing the number of AEs monitored will affect substantially neither overall patient safety nor compromise evaluation of regimens undergoing testing. We present several considerations for such a reduction in data collection, as well as a policy that we have used to address the deluge of RAE data.

Questionable value of attribution when interpreting adverse event data: A joint evaluation by North Central Cancer Treatment Group (NCCTG) and American College of Surgeons Oncology Group (ACOSOG)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6511-6511
Author(s):  
S. L. Hillman ◽  
D. J. Sargent ◽  
B. M. Bot ◽  
R. P. DeMatteo ◽  
E. A. Perez ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Controlled Trial ◽  
Study Drug ◽  
Phase Iii ◽  
North Central ◽  
Adverse Event Data ◽  
American College Of Surgeons ◽  
Version 2.0 ◽  
Asco 2006 ◽  
Joint Evaluation

6511 Background: In March 1998, the Common Toxicity Criteria (CTC) version 2.0 introduced the collection of attribution of adverse events (AE) to study drug. Collection of attribution adds time and cost to the clinical trial process, and reporting in the literature has varied. At ASCO 2006 results were presented from NCCTG trial 97–24–51 that showed ∼ 50% of events on the placebo arm were reported as attributed to study drug and 25% of the time the same event was not consistently attributed. We sought to validate these results in a second placebo controlled trial. Methods: Patients on the placebo arm of the phase III ACOSOG trial Z9001 (imatinib mesylate vs. placebo after resection of primary gastrointestinal stromal tumors) were evaluated since the reported AEs could not be due to study drug. Attribution was collected per CTCv3.0 as not related, unlikely, possibly, probably, or definitely related, and categorized as “unrelated” (not related or unlikely) and “related” (possible, probable, or definite). Patterns were evaluated using generalized estimating equations adjusting for multiple events per patient. Results: 202 patients and 2871 AEs were included. 52% of AEs were reported as “related”. Known imatinib AEs were more likely to be reported as “related”. The reported rate of AE relatedness varied by AE type. No patterns were observed by gender, age, PS, severity or visit of AE. When the same event was reported on the same patient on multiple visits, the attribution category changed at least once 33% of the time with 19% changing from “related” to “unrelated” or vice versa. Conclusion: 52% of events on the placebo arm of Z9001 were reported as attributed to study drug and 19% of the time the same event was not consistently attributed. These data provide further evidence that attribution is difficult to determine, unreliable, and of questionable value in interpreting randomized clinical trials. No significant financial relationships to disclose. [Table: see text]

Phase I/II trial of pyrazoloacridine and carboplatin in patients with recurrent glioma: A North Central Cancer Treatment Group trial

2005 ◽  
Vol 23 (5) ◽  
pp. 495-503 ◽  
Author(s):  
Evanthia Galanis ◽  
Jan C. Buckner ◽  
Matthew J. Maurer ◽  
Joel M. Reid ◽  
Mary J. Kuffel ◽  
...  
Keyword(s):  
Treatment Group ◽  
Phase I ◽  
Cancer Treatment ◽  
Recurrent Glioma ◽  
North Central ◽  
Group Trial

Medroxyprogesterone acetate (MPA) versus venlafaxine for hot flashes: A North Central Cancer Treatment Group trial

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 8014-8014 ◽  
Author(s):  
C. L. Loprinzi ◽  
R. Levitt ◽  
J. A. Sloan ◽  
S. R. Dakhil ◽  
D. L. Barton ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cancer Treatment ◽  
Medroxyprogesterone Acetate ◽  
Hot Flashes ◽  
North Central ◽  
Group Trial

Phase III double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea during pelvic radiation therapy: Results of North Central Cancer Treatment Group protocol N00CA

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8506-8506 ◽  
Author(s):  
J. A. Martenson ◽  
J. A. Sloan ◽  
R. L. Deming ◽  
D. B. Wender ◽  
K. J. Stien ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Treatment Group ◽  
Cancer Treatment ◽  
Randomized Study ◽  
Wilcoxon Test ◽  
Phase Iii ◽  
Double Blind Study ◽  
Double Blind ◽  
North Central ◽  
Pelvic Radiation

8506 Background: A randomized study (Int J Rad Oncol Biol Phys 54:195–202, 2002) demonstrated a beneficial effect for octreotide in the treatment of diarrhea in patients receiving pelvic radiation therapy. This North Central Cancer Treatment Group study was undertaken to determine the effectiveness of depot octreotide in the prevention of diarrhea during pelvic radiation therapy. Methods: Patients receiving pelvic radiation therapy, with a planned minimum dose of 45 Gy at 1.70–2.1 Gy per day, were eligible for this study. The study was designed for a Wilcoxon test, with 112 evaluable patients, to have 85% power to detect a further one grade decrease in diarrhea over and above that experienced by patients treated with placebo. Between June 13, 2002 and October 28, 2005, 120 evaluable patients were randomly allocated, in double blind fashion, to receive octreotide (62 patients) or placebo (58 patients), prior to the fourth radiation therapy fraction. Octreotide dosing: Octreotide, 100 micrograms subcutaneously on day 1 followed by depot octreotide, 20 milligrams intramuscularly on days 2 and 29. Results: Grade 0, 1, 2 and 3 diarrhea was observed in 17%, 32%, 26% and 26% of patients treated with octreotide and 18%, 34%, 22%, and 26% of patients treated with placebo (P=0.86). Grade 0, 1, 2 and 3 tenesmus was observed in 55%, 30%, 11% and 4% of patients treated with octreotide and 76%, 16%, 4%, and 4% of patients treated with placebo (P=0.04). No other statistically significant differences in toxicity were observed. Conclusions: Octreotide, as administered in this study, did not decrease diarrhea during pelvic radiation therapy. [Table: see text]

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