Current federal regulations require ongoing oversight and monitoring of adverse events in order to ensure the safety of participants and the validity and integrity of data. A description of the plan for reporting non-serious anticipated and unanticipated adverse events as well as serious adverse events to the IRB, CRC, funding and regulatory bodies, should be included in a DSMP.
Any unanticipated problem involving "risk" that ultimately results in harm to the subject's rights or well-being and that is related to a research intervention constitutes a reportable adverse event. At UTMB, all adverse events that are unanticipated and/or serious require reporting within 24 hours. All CRC investigators must follow the UTMB IRB Adverse Event Policy. In addition, serious adverse events associated with CRC protocols must be reported orally and in writing immediately by the PI (or monitor in his/her absence) to:
Dr. Don W. Powell, Program Director of the CRC
Professor of Internal Medicine and Neuroscience and Cell Biology
Telephone: (409) 772-0752
The PI and/or the Data and Safety Monitoring Board will make an assessment of the relationship between the adverse event and the protocol/intervention for each adverse event occurrence. Investigators should follow the IRB terminology if available.
An Adverse Event (AE): is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an experimental medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure. An Adverse Event is any experience that has taken place during the course of a research project, which, in the opinion of the investigators, was harmful to a participant, increased the risk of harm, or had an unfavorable impact on the risk/benefit ratio of the study.
Anticipated (Expected) Adverse Events: these are risks or events reported in the Investigator's Brochure and listed in the consent form. The UTMB IRB and the CRC will consider an adverse event as "anticipated" or "expected" only if it is discussed in the protocol and included in the Informed Consent document.
Unanticipated (Unexpected) Adverse Events: an unanticipated adverse event is any unexpected untoward event or medical occurrence in a study subject that is not consistent with the known, predicted possible effects of the research protocol. An unanticipated adverse event can therefore be any unanticipated, unfavorable, and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study that was not listed in the protocol, consent form or investigator's brochure. This includes any experience that suggests a significant hazard, contraindication, side effect, or precaution. In addition to this definition, the UTMB IRB and the CRC interpret any adverse event not included in the Informed Consent document as a risk to be "unanticipated" or "unexpected." [Adapted from HHS & FDA 21 CFR 312.62 (6), 21 CFR 50.27 (a), 21 CFR 312.32 (a), FDA Docket No. 93N-0181].
Serious Adverse Event (SAE): Serious adverse events are defined by regulatory criteria and include any of the following:
The NIH Web site detailing serious adverse events/effects
0 = No Adverse Event or within normal limits
1 = Mild Severity: Transient laboratory test alterations; discomforts noted but no disruption of daily activities; no therapy, or only symptomatic therapy required
2 = Moderate Severity: Laboratory test alterations indicating injury without long-term risk; discomfort sufficient to modify normal daily activity; specific therapy required (i.e., more than symptomatic)
3 = Serious Severity: Laboratory test indicating a serious health threat or permanent injury; incapacity, inability to work, inability to perform normal daily activity; hospitalization required or prolonged; emergency treatment required; life-threatening events; death
Note: Investigators may use other grading scales such as the National Cancer Institute Common Toxicity Criteria.
Human Subject Regulations Decision Charts (OHRP)
International Human Subjects Research:
Canadian Institute of Health Research
International Conference on Harmonization
The World Medical Association
Office for Human Research Protections
Of Interest to Human Subjects of (Participants in) Biomedical Research:
National Institutes of Health / National Library of Medicine: Information about Clinical Trials
Centerwatch Clinical Trial Listing Service
Public Responsibility in Medicine and Research
National Institutes of Health Homepage
DHHS: Office for Human Research Protections
FDA: Protection of Human Subjects
National Library of Medicine: Gateway Search Page
Annotated Compendium of NIH Resources on Informed Consent (NIH)