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)
Reportable Problems
UAB policy requires that "unanticipated problems involving risks to research subjects or others" be promptly reported to the IRB, the Institutional Official, the sponsor, and appropriate federal agencies. Others, in "research subjects or others," includes investigators, research staff, or other individuals affected by the research project.
In accord with that policy, the IRB has published a list of problems (below) that investigators must report to the IRB. The Principal Investigator must report the problems listed to the IRB within the timeframes indicated. The IRB may request further information as necessary and will determine whether any research project that has been associated with unexpected serious harm to the participants must be terminated.
Investigators are responsible for meeting all reporting requirements that apply to their projects. For example, investigators have reporting responsibilities to sponsors of FDA-regulated research. Investigators serving as sponsors of FDA-regulated research have additional reporting responsibilities (see FDA-Regulated Research).
Investigator Reports to the IRB
Adverse events and safety reports that require prompt reporting should be submitted to the IRB using the Problem Report form. If the event being reported leads to a change in the informed consent document, see "Changes in the Informed Consent Document" in Revisions & Amendments.
Within 5 Working Days
As soon as possible but in all cases within 5 working days, the investigator must report to the IRB:
- Any changes to the protocol that were taken to eliminate an apparent hazard to a participant in an emergency.
- 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.
- Any emergency use of an FDA-regulated test article or Humanitarian Use Device prior to IRB approval.
Within 10 Working Days
As soon as possible but in all cases within 10 working days, the investigator must report to the IRB:
- Any adverse event occurring at a performance site under UAB IRB oversight that, in the opinion of the principal investigator, is both unexpected and related or possibly related to the research.
- Information that indicates a change to the risks or potential benefits of the research. For example:
- An interim analysis or safety monitoring report indicates that frequency or magnitude of harms or benefits may be different from those initially presented to the IRB.
- A paper is published from another study that shows the risks or potential benefits of the research might be different from those initially presented to the IRB.
- A breach of confidentiality.
- Change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol.
- Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a research subject.
- Incarceration of a subject enrolled in a protocol not approved to enroll prisoners.
- Event that requires prompt reporting to the sponsor.
- Sponsor-imposed suspension for risk.
- Complaint of a subject when the complaint indicates unexpected risks or cannot be resolved by the research team.
- 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.
- Safety monitoring reports and DSMB reports from the sponsor.
At the Time of Continuing Review
Along with the Investigator's Progress Report and other materials described in the section on Continuing Review & Approval, the investigator must report to the IRB:
- Summary on the Problem Summary Sheet of all adverse events at performance sites under UAB IRB oversight.
- Summary on the Problem Summary Sheet of all problems reported to the UAB IRB, including serious adverse events.
- Safety monitoring or DSMB reports received from sponsor and not previously forwarded to the IRB, if any. The investigator will be notified in writing if the IRB requires that all such reports be submitted for continuing review.
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.
Definitions Related to Research-Related Problems
The "correct" terminology for an event can vary because different agencies use different terms. For example, a "serious adverse drug experience" under FDA regulations may or may not be an "unanticipated problem involving risks to subjects or others" under DHHS regulations. To help investigators plan their strategies for reporting, this section defines these terms in relation to UAB requirements. Unanticipated problems involving risks to research subjects or others includes any incident, experience, or outcome that meets all of the criteria below:
- Is unexpected in terms of nature, severity, or frequency given
- the research procedures that are described in the protocol-related documents, such as the IRB-approved Human Subjects Protocol and informed consent documents; and
- the characteristics of the subject population being studied; and
- 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
- Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
Adverse event is 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 (includes serious adverse drug or biological experience and unanticipated adverse device experiences under FDA regulations) is any adverse event temporally associated with the subject's participation in research that meets any of the following criteria:
- Results in death
- Is life-threatening (places the subject at immediate risk of death from the event as it occurred)
- Requires inpatient hospitalization or prolongation of existing hospitalization
- Results in a persistent or significant disability/incapacity
- Results in a congenital anomaly/birth defect
- 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 listed in this definition. Examples include allergic bronchospasm requiring intensive treatment in the emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, and the development of drug dependency or drug abuse.
Forms
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.