Study-Specific Adverse Event(AE) Reporting Plans
There are two types of studies for which the principal investigator should consider using a study-specific AE reporting plan in order to reduce or streamline the reporting burden on the study team:
- Sponsored studies that include a detailed AE reporting plan for submitting adverse events to a sponsor and/or a data safety committee.
- Minimal to moderate risk studies that do not fall under FDA oversight.
Sponsored Studies
The first type benefits from using a study-specific plan because the sponsor's plan can be followed for both the sponsor and the IRB, thus allowing the study team to streamline their efforts. Instead of referring to multiple documents to determine when an event must be reported the study team simply looks to the protocol. The IRB does not have to be named explicitly-the IRB guidance states that the report to the IRB is due concurrently with the report to the named oversight entity.
In order for the sponsor's AE reporting plan to be acceptable, it must describe the types of AEs to be reported and specify the timeframe for reporting them. For example, "Hospitalizations must be reported within three days." A sponsor plan that states, "All AEs will be reported in a timely manner" would not be acceptable.
Urgent Reports
Since many sponsored plans require the study team report to the sponsor within 24 hours, the investigator may choose to request approval of a modification to the 'concurrent' IRB report by stating in the free-text box of question 32-1.2.1 in the eResearch application that "wherever the protocol indicates reports to the sponsor will be made within 24 hours, the corresponding report to the IRB will be made within 7 days." An investigator could also delinate a more detailed exception plan. These requests may be made for studies using the UM Standard AE Timetable as well as those choosing a Study Specific Timetable.
Minimal to Moderate Risk Studies
The UM Standard Timetable for reporting adverse events adheres to the most stringent federal requirements for reporting. For studies that are lower risk and do not involve FDA oversight* a less rigorous plan can still provide subject protections while reducing study team burden by eliminating the requirement to report AEs that are not attributable to the research (i.e. unrelated AEs or expected AEs attributable to the subjects' underlying condition).
The suggestions below typically apply to human subject research that is lower risk such as studies involving:
- observation
- limited interaction with subjects (e.g. interview then prospective collection of clinically collected data for two years; fMRI)
- 'minimal' to 'minor over minimal' risk procedures (e.g. cheek swabs, blood draws, punch biopsies, surplus tissue collection).
- interventions that differ significantly from standard clinical trials of FDA-regulated drugs or devices (e.g. focus groups)
- longitudinal study
- survey
Suggestions for Writing a Study Specific Adverse Event Reporting Plan
A study-specific AE Reporting plan should describe which AEs will be reported. AEs may be described in a very specific list that relates to the research. For other projects it may be more appropriate to describe the AEs in a general, rather than a specific way.
Make sure the AE Reporting is explicit in stating that any AEs with a causal relation to the research will be reported and adopt the timing on the IRBMED Standard Timetable for those AEs.
It is often helpful to also indicate AEs or types of AEs that will not be reported. For example, designate predictable events for the population being studied that are not attributable to the research as events that will not be reported as AEs, even if the data is collected for study purposes (e.g. death in a elderly population with a history of stroke and diabetes; incarceration in a longitudinal study of drug abusers).
Separate aspects of the AE reporting plan into categories when appropriate (e.g. separate descriptions or tables for different cohorts). Designate what will and will not be reported using terminology as general or as specific as is appropriate.
The AE reporting plan may be submitted as a standalone document, as part of a data and safety monitoring plan (DSMP) , or as part of a protocol.
Example #1
The example that follows is for a (hypothetical) study of parents with a history of violence and their infants where the research itself involves a cheek swab for genetic testing, review of criminal records, and 12 interviews conducted at six-month intervals after birth of the firstborn child.
AE Reporting to the IRB
Infant Subjects |
|
Reportable Events |
Timing of Report to IRBMED |
Serious-within 7 days Non-Serious-with scheduled continuation |
|
Any physical, social, economic, or psychological harm attributable to participation in this research study (e.g. an injury occurring during a study visit, breech of confidentiality, auto accident en route to or from research visit) |
Serious-within 7 days
Non-Serious-with scheduled continuation |
Documented** physical injury caused by parental abuse |
With SCR* |
Unrelated death while on study |
With SCR |
| Non-Reportable Events | |
|
|
Adult Subjects |
|
Reportable Events |
Timing of Report to IRBMED |
Unanticipated problem involving risks to subjects or others |
Serious-within 7 days Non-Serious-with scheduled continuation |
Any physical, social, or psychological harm attributable to participation in this research study (e.g. an injury occurring during a study visit, infection at the site of a blood draw if antibiotics are required) |
Serious-within 7 days
Non-Serious-with scheduled continuation |
Documented** physical injury caused by spousal abuse |
With SCR |
Death while on study |
With SCR |
Loss of job or insurability due to breach or revelation of research records or participation |
Within 7 days of notification |
Related separation or divorce |
Within 14 days of notification |
| Non-Reportable Events | |
|
|
- *Scheduled continuation review (renewal application)
- **'Documented' means that the information is verified by a physician, hospital, police, or Child Protective Services report.
- Serious = an event requiring hospitalization, permanent disability, incarceration, significant familial disruption (e.g. separation, divorce), job loss
- Non-Serious = an event requiring some medical, psychological, psychiatric or similar attention to resolve.
Example #2
This example is for a study that involves surveys of adult subjects and their caretakers. This AE reporting plan is part of the study's data and safety monitoring plan (DSMP) rather than a stand alone document.
Data and Safety Monitoring Plan
Risks
The foreseeable risks and their likelihood include:
- Inappropriate invasion of privacy (rare)
- Data loss or breach of confidentiality (rare)
- Emotional upset
Steps to Reduce and Monitor Risks
- All study team members will be trained in privacy, confidentiality, and security measures including but not necessarily limited to:
- PEERRS Human Subject Module
- UMHS HIPAA training
- Data will not be stored outside of the principal investigator's office
- Data will not be transferred to PDAs, laptops, CDs, flash drives, etc.
- Laboratory will be locked when vacant
- Computers and all storage devices will be password-protected
- MSIS and/or MCIT will provide security consultation and support
- Surveys will provide a 24/7 phone number whereby members of the study team can be paged for emotional upset
- Study team members who serve on-call will be trained in crisis management and have the skills to assess suicidality or other need for professional intervention.
- Study team will keep a list of agencies and services for subject referral
Plan for Reporting Adverse or Other Reportable Events or Information
Only related adverse events will be reported. " Related means events that are caused by the research itself, not the disease or population under study. Reports will be sent to the IRB as follows:
- Adverse event is defined as "serious"-- report to the IRB within 7 days
- Non-serious adverse events grade 2 or higher (emotional upset not requiring intervention) report to IRB prior to SCR
- Any unanticipated problems that are related to the study and indicate risks to subjects-serious problems within 7 days, non-serious problems within 14 days
- Privacy violation or breech of confidentiality-report to IRB within 7 days, within 24 hours to the UMHS Privacy Office
- Protocol deviations-report with SCR
FAQs
Q: The Standard Timetable for reporting adverse events requires us to report adverse events that are not related to the research we are conducting. Do we still have to follow it?
A: Yes, unless the study includes or is amended to include an AE reporting plan that is approved by the IRBMED for that study. Studies that do not involve drugs or devices subject to FDA oversight may be appropriate for a different reporting scheme, but only after the IRBMED has given its approval.
Q: How do we amend the study to include an AE reporting plan?
A: Write an AE reporting plan appropriate for your study.
For older studies using the IRBMED Legacy (paper) application, submit the AE reporting plan with a Previously Approved Project Application sections 1-3 and 8.
For studies in eResearch, in the amendment cover sheet indicate that an AE reporting plan is being added to the study. In the application, section 32-1.2, toggle the 'study specific guidelines' radio button and complete the questions as indicated. In 32-1.2.2 upload the AE reporting you wrote for the study.
You should only implement the plan AFTER receipt of a 'Notice of Outcome' indicating IRB approval.
Updated 10/2/07
