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Adverse Event Reporting
Session 4: Adverse Event Reporting
Deborah A. Zarin, M.D.
Adverse Events - Default
- If the Secretary fails to issue regulation by 24 months after the date of enactment [September 2009]
- SERIOUS ADVERSE EVENTS
- Table of anticipated and unanticipated serious adverse events
- Grouped by organ system
- Number and frequency of event in each arm of clinical trial
- FREQUENT ADVERSE EVENTS
- Table of anticipated and unanticipated adverse events
- Exceed a frequency of 5 percent within any arm of clinical trial
- Grouped by organ system
- Number and frequency of event in each arm of clinical trial
Published Adverse Events
Table 4: Adverse Events Occurring With a Frequency of at Least 2.0%
Esomeprazole (n = 1205) | Omeprazole (n = 1200) | |
---|---|---|
No. (%) of Patients | ||
Headache | 75 (6.5%) | 70 (5.8%) |
Diarrhea | 47 (3.9%) | 56 (4.7%) |
Nausea | 36 (3.0%) | 36 (3.0%) |
Abdominal Pain | 31 (2.6%) | 32 (2.7%) |
Results Record
Adverse Events
Esomeprazole N-1,205* | Omeprazole N=1,200 | |
---|---|---|
Serious Adverse Events | N/A | N/A |
Frequent Adverse Events (>5%) Nervous System Disorders Headache |
75 (6.2%) | 70 (58%) |
Gastrointestinal Disorders Diarrhea Nausea |
67 (5.6%) 61 (5.1%) |
66 (5.5%) 57(4.8%) |
*Of the 2.425 patients with erosive esophagitis randomized to study medication, 2,405 patients received at least one dose of either esomeprazole (n = 1,205) or omeprazole (n = 1,200)
Issues in Reporting Adverse Event Data
- Definitions: AE, serious AE
- Characteristics to consider
- Frequency (threshold)
- Attributable?
- Statistically significant?
- # assessed (and time frame)
- Systematically assessed?
- How to count and how to report
- Splitting vs. lumping
- Recurrent events in same patient
Frequency
- US Public Law 110-85 Default: Frequent AEs
- AEs that exceed a frequency of 5%
- CONSORT
- Poor reporting practice: "Reporting only the adverse events observed at a certain frequency or rate threshold (for example, >3% or >10%)."
- FDA – Adverse Reactions Section of Labeling – General Principles for Presenting Adverse Events in a Table
- The frequency cutoff for the listing of common adverse reactions identified from clinical trials (usually the adverse reactions table) must be appropriate to the safety database
- Factors that could influence selection of a frequency cut-off include the size of the safety database, the designs of the trials in the database, and the nature of the indication. The frequency cutoff should be noted in the listing or table header, in the text accompanying the listing or table, or in a footnote.
- The frequency cutoff for the listing of common adverse reactions identified from clinical trials (usually the adverse reactions table) must be appropriate to the safety database
Ann Intern Med. 2004;141:781-788
FDA Guidance for Industry - Adverse Reactions Section of Labeling for Human - Prescription Drug and Biological Products — Content and Format Proposed Approach
Key Implementation Issues
- Default v. regulation
- Default as voluntary “pilot” to inform rulemaking?
- Timing of submissions—relationship to completion date and outcome measures
Example
- A Phase III, Randomized, Open-Label, Multicenter Study Comparing GW572016 [lapatinib] and Capecitabine (Xeloda) versus Capecitabine in Women with Refractory Advanced or Metastatic Breast Cancer
- GlaxoSmithKline
- Sources:
- GSK clinical trial register
- New England Journal of Medicine
- Drugs @ FDA: Lapatinib label
GSK Clinical Trial Register
GSK Clinical Trial Register
New England Journal of Medicine
N Engl J Med 2006;355:2733-43
Table 3 shows adverse events through November 15, 2005, according to the treatment received.
FDA Approved Label
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National Institutes of Health, Health & Human Services
Freedom of Information Act, NLM Customer Support
Last reviewed: 30 December 2016
Last updated: 30 December 2016
First published: 24 March 2008
Last updated: 30 December 2016
First published: 24 March 2008