Under the terms of UAB's FWA, research involving human subjects is reviewed in accordance with HHS regulations (45 CFR Part 46) and any other applicable regulations, laws, and policies. When the FDA has oversight of the research, FDA regulations (CFR Title 21) must be followed in addition to the HHS regulations.
This section of the guidebook contains many of the requirements that investigators, sponsors, and IRBs must fulfill in the conduct and review of FDA-regulated research. However, investigators on such studies should become familiar with the regulations as published (Code of Federal Regulations through Government Printing Office).
Investigational Drugs or Biologics: Investigational New Drug (IND)
INTRODUCTION/ PI RESPONSIBILITIES:
Federal Regulations [45 CFR 46.103(b)(5) and 21 CFR 56.108(b)(1)] and UAB IRB policy (POL006) requires Principal Investigators of all human subject’s research (FDA-regulated or not), and their designated study teams must report any unanticipated problems involving risks to research subjects or others be promptly reported to the IRB.
Events that meet the IRB’s reporting criteria should be promptly submitted to the IRB using the electronic Problem Report Form. See the timeline table below.
If the IRB determines that a reported event constitutes an UPIRSO, it promptly reports its determination and actions to the investigator and the Institutional Official. The Institutional Official, in turn, is responsible for promptly reporting the IRB findings to the sponsor and applicable federal agencies.
Note: Investigators serving as sponsors of FDA-regulated research have additional reporting responsibilities (see FDA-Regulated Research).
DEFINITIONS:
This section defines these terms in relation to UAB IRB requirements.
Reportable Event: A reportable event is any unanticipated problem, adverse event or other incident that has the potential to be classified by the IRB as an unanticipated problem posing risks to participants or others.
Unanticipated Problem Involving Risks to Subjects or Others (UPIRSO): An unanticipated problem is any incident, experience or outcome that meets all three of the following criteria:
- It is unexpected (in terms of nature, severity, or frequency) given (a) the research procedures described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied.
- It is related or possibly related to participation in the research (possibly related means there is some likelihood in the judgment of a reasonable investigator that the incident, experience, or outcome may have been caused by the procedures involved in the research); and
- The event suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, social, economic, legal, or informational harm) than was previously than was previously known or recognized.
NOTE: Unanticipated problems that meet the three criteria above, will often warrant consideration of substantive changes in the research protocol or informed consent process/document or other corrective actions in order to protect the safety, welfare, or rights of subjects or others.
Adverse Event: Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory findings), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subjects’ participation in research. Adverse events encompass both physical and psychological harms.
Serious Adverse Event: Any adverse event temporally associated with the subject's participation in research (including serious adverse drug or biological experience and unanticipated adverse device experiences under FDA regulations) that meets any of the following criteria:
- When the outcome results in death.
- Is life threatening (places the subject at immediate risk of death from the event as it occurred).
- Requires admission to the hospital or prolongation of existing hospitalization.
- Results in a persistent or significant disability/incapacity.
- Results in congenital anomaly or birth defect.
- For Medical Devices: requires medical or surgical intervention to prevent permanent impairment or damage.
- Event that changes the risk/benefit ratio of the study
- Any other adverse event that, based upon appropriate medical judgment, may jeopardize the subject's health, and may require medical or surgical intervention to prevent one of the other outcomes previously listed. Examples include an allergic reaction requiring treatment in an ER, seizures/convulsions, development of drug dependence or drug abuse, suicide attempt, etc.)
For more information visit: https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event
REPORTING TIMEFRAME:
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5 Working Days |
10 Working Days |
At Continuing Review |
Any changes to the protocol that were taken to eliminate an apparent hazard to a participant in an emergency |
Any adverse event occurring at a performance site under UAB IRB oversight that, in the opinion of the PI, is both unexpected and related (or possibly related) to the research |
All adverse events at performance sites under UAB IRB oversight. |
Any deviations from the investigational plan for an investigational device taken to protect the life or physical well-being of a participant in an emergency |
Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a research subject |
All problems reported to the UAB IRB, including serious adverse events. |
Any emergency use of an FDA-regulated test article or Humanitarian Use Device prior to IRB approval |
Information, including adverse events or safety reports, that indicates a change to the risks or potential benefits of the research. For example:
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Safety monitoring or DSMB reports received from sponsor and not previously forwarded to the IRB, if any. |
Change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol |
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A breach of confidentiality |
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Incarceration of a subject enrolled in a protocol not approved to enroll prisoners. |
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Event that requires prompt reporting to the sponsor. |
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Sponsor-imposed suspension for risk |
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Unresolved participant compliant |
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Protocol violation (i.e., an accidental or unintentional change to the IRB-approved protocol) that harmed subjects or others or that indicates subjects or others may be at increased risk of harm |
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Safety monitoring reports and DSMB reports from the sponsor. NOTE: These should be submitted via Amendment. |
IRB & Institutional Reporting
If the IRB determines that a reported event constitutes an unanticipated problem that alters the risk of the research, it promptly reports its determination and actions to the investigator and the Institutional Official. The Institutional Official, in turn, is responsible for promptly reporting the IRB findings to the sponsor and applicable federal agencies.
No protocol, informed consent process, or informed consent document may be modified without prior approval from the IRB unless it is necessary to eliminate an apparent and immediate hazard to one or more of the participants.
Modification means any change. It encompasses two commonly used terms: A revision is a change in something that exists, such as increasing the number of participants. An amendment adds something new, such as a person who will obtain informed consent.
Commonly Reviewed Modifications
The list below includes some common modifications that the UAB IRB reviews:
- A change in the procedures of the protocol, such as
- when the inclusion/exclusion criteria change
- when a genetic or sample-storage component is added or changed
- when the protocol is no longer open for enrollment of new participants
- when a sponsor temporarily suspends enrollment
- when the protocol ends
- A change in the procedures used to recruit or enroll participants, such as
- New or newly revised advertisements
- New or newly revised script or questionnaire for screening
- A change in the circumstances under which informed consent is discussed or obtained
- A change in the wording or format of the informed consent document
- Changes in study personnel, such as
- Adding or removing an investigator
- Adding or removing key personnel
- Adding or removing persons who are involved in the informed consent process
- Changing the Principal Investigator.
Application Procedures
Any planned modification must be submitted to the IRB for review and approval before being implemented or used with participants. In the rare cases where a change is necessary to eliminate a hazard, the investigator has 5 working days in which to report the modification to the IRB.
Investigators submit a Revision/Amendment using the e-Portfolio or the standalone Revision Amendment e-form in IRAP to review any protocol change—including changes undertaken as necessary to eliminate a hazard. Some modifications require that the investigator include materials in addition to the Revision Amendment e-form. For example, sponsors often initiate improvements in procedures or documents used with participants. In these cases, the investigator also provides the IRB with a copy of all investigator-sponsor correspondence and other documents related to the change.
Change in Principal Investigator
The outgoing investigator submits the Personnel Amendment e-form. In addition, the following written and signed notifications must be submitted:
- The current Principal Investigator notifies the IRB that they have relinquished the responsibilities of Principal Investigator to the person named or will do so on a specified date.
- The newly named Principal Investigator notifies the IRB that they have read the protocol and agree to accept the responsibilities of the Principal Investigator.
Changes in the Informed Consent Document
When a modification makes it necessary to change the informed consent document, regardless of whether any participants are enrolled, include two copies of the revised consent form:
- One “track changes” copy shows all previous versions’ changes. The track change function is available in most word-processing software. You may “markup” copy showing all changes by highlighting all additions and striking through all the deletions.
- One “clean” copy for the IRB-approval stamp, without tracked, highlighting, or outdated text.
Addendum Informed Consent Documents
If participants have already signed a consent document and it becomes necessary to inform them of modifications or new information, an addendum informed consent document may be necessary when:
- The protocol is open for recruitment and enrollment
- Some participants are already enrolled and
- The change might be related to the participants’ willingness to continue their participation in the study;
OR
- The protocol is closed to enrollment and
- The change might be related to the participants’ willingness to allow the continued use of data from their participation.
The FDA does not require re-consenting of participants who have completed their active participation in the study, or who are still actively participating when the change will not affect their participation, for example when the change will be implemented only for subsequently enrolled participants.
Further Information
Please direct any questions about modifications to the protocol, informed consent process, or informed consent document to the OIRB (934-3789,
Investigators submit all applications for initial review to the OIRB. Depending upon the type of sponsor and type of review, the OIRB may coordinate review by one of the other IRBs that UAB is authorized to use (a commercial IRB such as WIRB, or Advarra).
Industry-sponsored protocols are typically reviewed by a commercial unless the protocol:
- Is eligible for NHSR, Exempt, or Expedited review
- Is sponsor-investigator (i.e., investigator-initiated) research or
- Involves gene transfer or other types of novel, high-risk research.
Note: Investigators whose protocols are sent to a commercial will have conflict of interest review by both the UAB CIRB and the commercial IRB.
WIRB Fees
The WIRB fee schedule should be treated as confidential. It is available from the UAB single IRB Liaison, Ms. Vanessa Champigny, by calling the OIRB at (205) 934-3789.
UAB Study Management Fees
Industry-funded clinical trials are subject to the UAB study management fees. Investigators should inform potential sponsors of this fee during contract negotiations.
Please refer to the following web address for additional information: https://www.uab.edu/research/home/osp-industry-projects/clinical-trials/fees.
Please direct questions about WIRB review and industry sponsors to the UAB single IRB Liaison: Ms. Vanessa Champigny (
Forms
See the IRB Meeting Schedule for submission deadlines of materials for continuing review.
- one copy of the consent with tracked changes, if applicable, and
- one "clean" copy of the consent with changes accepted. Leave ample space in the upper left-hand corner of the consent for the IRB approval stamp.
- The Investigator’s Progress Report
- If the protocol is open to enrollment of new participants or participants are being "re-consented" with an addendum form, submit:
- A copy of the revised consent document with tracked changes (document name: consent.tracked.yymmdd) and
- A "clean" copy for the IRB approval stamp (document name: consent.clean.yymmdd).
- The Problem Summary Sheet, if applicable.
- Any reports not previously submitted for IRB review, if applicable.