University of New Mexico Health Sciences Center
The HRRC monitors ongoing research through numerous mechanisms including prospective review of changes to the research, review of unanticipated problems, adverse events and safety reports, review of protocol violations/deviations and investigator non-compliance. The HRRC may also choose to observe the consent process and/or audit the research records.
The HRRCs review requests for amendments to previously approved projects during their meetings. Investigators are not permitted to implement any amendments without approval by an HRRC except to eliminate apparent immediate hazard to the subjects. 45 C.F.R. 46.103(b) (4); 21 C.F.R. 56.108(a)(4). Such actions must be reported so the HRRC may review them to determine whether the changes were consistent with ensuring participants’ continued welfare as well as approve the amendment for the future. These actions must be reported by submitting an amendment/change form and memo (if necessary), proposed consent form, any supporting documents that will assist the HRRC in understanding the revision as well as an event/unanticipated problem reporting form describing the protocol deviation. Investigators should be aware that a change in risks and benefits may require a change in the consent form and re-consenting of subjects. If any revisions or addenda require changes to a consent form, investigators are required to update the version date on the revised consent form, under the HRRC number.
Because only minor changes that do not affect the degree of risk, and that do not raise any other concerns, may be approved by the HRRC through the expedited review procedure, investigators should submit the number of copies required for initial review.
The date of approval of an amendment does not change the date by which the regularly scheduled continuing review of the project is to be completed.
Data already collected for research may be useful in answering new questions that are generated during the course of data analysis. If new/different objectives (use of data) are identified from that which was originally approved, it is required that the newly defined research question(s) be submitted to the HRRC. This can be done by completing an Amendment/Change form and a revised protocol, if appropriate. HRRC review of new research questions is required for several reasons, including assuring 1) that proper informed consent was obtained, 2) that publications will not result in stigmatization of a subject population, and 3) that the research is consistent with the ethical principles of human subject research.
The DHHS and FDA regulations require prompt reporting of unanticipated problems involving risks to subjects or others. However the regulations do not specifically define unanticipated problems involving risks to participants or others.
The following are examples of unanticipated problems involving risks to subjects or others and therefore require reporting to the HRRC and may require reporting to FDA or OHRP/DHHS. The investigator should report in writing:
Definitions
Harm: The infliction of anything detrimental to one’s privacy, rights, comfort, health, property or success resulting in pain, suffering, or loss. Harms may include death and injury or damage to one's psychological, social, economic or legal status. Harms may affect individuals as well as specific population subgroups.
Unanticipated: An event is “unanticipated” when it was unforeseeable at the time of its occurrence. The word unanticipated, is not a synonym for unexpected. A research protocol can monitor for an unexpected event, but cannot monitor for an unanticipated event. All unanticipated events are unexpected, but not vice versa.
Unanticipated Problem Involving Risks to Participants or Others: Any event that (1) is unanticipated, (2) caused harm or placed a person at increased risk of harm, and (3) is related to the research procedures.
Reporting a Reportable Event - Events that require reporting to the HRRC (as per section 8.2.1) should be reported using the Event Form. This form must be compleely filled out and signed/dated by the principal investigator. A co-investigator may sign in the PI's absence so as not to delay reporting. Supporting documentation should be attached to the event form. A copy of the applicable pages(s) of the current informed consent document should also accompany the event packet.
Reporting a Non-Reportable Event - Investigators must assess all events that occur during the course of the research to determine if they meet reporting criteria (1. Unanticipated, 2. Caused harm or placed a person at increased risk of harm, AND 3. Was more likely than not related to the research). If the three criteria are not met, Investigators should keep a copy of the completed Tracking Log for Non Reportable Events (attached to supporting documentation in their regulatory binder as part of Good Clinical Practice (GCP). This will provide documentation that all events were assessed and did not meet reporting criteria. If the three criteria are met, then an Event Form should be completed and submitted to the HRRC.
The HRRC no longer accepts IND safety reports that do not meet all three reporting criteria..
Investigators must report events to the HRRC as soon as possible but no later than 5 days from the event date or “site awareness date”
All events received by HRRC are reviewed by a Human Protections Specialist (HPS). Those events that meet the criteria of an unanticipated problem involving risks to subjects or others will then be reviewed by an HRRC Chair who will determine whether it must be presented to a fully convened committee. HRRC review of events focuses on whether risks to human subjects may have changed. HRRC also determines if changes to the protocol are required, how research participants' will be informed of a newly identified risk, if the consent document requires revisions, if there is a need to increase safety monitoring of the project, or if the study should be terminated.
The HRRC may require that the investigator notify subjects of unanticipated findings or risks. If this is a directive, the PI will be notified in writing. Subject notification may be required to be in the form of a letter sent to all subjects and/or as part of a revised informed consent document to be signed by all current and new subjects.
In its discretion, and dependent upon the perceived risk of the research, an HRRC may require more active monitoring of a research project (e.g. by requiring a data monitoring committee to review the research project). Human research conducted in the GCRC requires a Data Safety Monitoring Plan (DSMP). Final DSMPs are submitted by the GCRC to the HRRC for review.
In addition, any research being conducted under an FDA/OHRP waiver of informed consent for acute care research requires the establishment of an independent data monitoring committee. 21 C.F.R. Section 50.24.
To remain active, all protocols must be reviewed no less than annually. The HRRC may require more frequent reviews if it considers that more oversight is necessary due to the nature of the study, vulnerability of the population, or degree of risk. The investigator will be informed upon approval of when the next review must be obtained, and will be reminded prior to expiration of the approval period. However, it is the investigator’s responsibility for ensuring his/her project is reviewed on time.
The principal investigator should submit a completed Progress/Closure Report not later than 30 days prior to the expiration date. The purpose of continuing review is to determine the appropriateness of permitting the project to continue, not solely to review any new developments, and therefore the same general criteria set forth in Section 6 are applicable. To make this determination, the HRRC requires information on, among other things, summaries of adverse events or unanticipated problems involving risks to subjects or others or withdrawals, a current risk-benefit assessment based on study results, and a summary of any changes that may affect the study. To allow for substantive and meaningful continuing review by the HRRC, the PI is required to submit an electronic copy of the current protocol to the HRRC. The protocol should reflect any amendments and changes previously approved by the HRRC. The current protocol and Progress/Closure Report from the investigator provide the HRRC with relevant information to determine whether the proposed research continues to fulfill approval criteria. The current protocol should be sent to HRRC@salud.unm.edu. Enter HRRC# in e-mail “subject” line as follows: i.e. HRRC# 04-001 Smith.
Projects that required full board review generally require full board continuing review unless the projects have changed such they now fall within the categories permitted to be reviewed by expedited review, Section 5.2. Further, if a study is closed to accrual and intervention is completed but for the collection of follow-up data, the study may be reviewed through the expedited review process.
When continuing review of research does not occur prior to the end of the approval period specified by the HRRC, HRRC approval expires automatically. Failure to submit progress reports in a timely manner is considered non-compliance (See Section 2.6.) If an investigator has failed to provide a Progress/Closure Report to the HRRC or the HRRC has not reviewed and approved a research study by the expiration date specified by the HRRC, the research must stop, unless the HRRC finds that it is in the best interests of subjects to continue participating in the research interventions or interactions. Enrollment of new subjects cannot occur after the expiration of HRRC approval.
If HRRC approval expires the HRRC office will send a “Notice of Study Expiration” to the PI informing the investigator that all research activity must cease as of the date of expiration. The PI must immediately submit to the HRRC Chair, a list of research subjects (using subjects initials only) for whom discontinuation of the research would cause harm and state the specific reason the subject should remain on the study. The HRRC Chair (with appropriate consultation of the VAMC Chief of Staff, if applicable) will determine if the subject(s) may continue in the research.
The PI must request reactivation or closure of an expired study within 10 working days of the “Notice of Expiration”. The HRRC must review and approve the reactivation request before the research may resume.
No new study will be accepted for a PI if there is documentation deemed outstanding/pending for any expired study.
To allow for substantive and meaningful review at the close of a study, the investigator is required to submit a Progress/Closure Report. This report updates the HRRC on the conduct and outcomes of the study, including enrollment numbers, withdrawals, complaints, and any risks that arose which may need to be disclosed to the subjects who had participated.
HRRC approval must be maintained and closure of a study may not occur unless 1) local enrollment to the study is closed, 2) all local research related interventions are complete, 3) all local participant follow-up is complete and 4) all individually identifiable information has been removed from study records. If a study is only in the period of data analysis or manuscript preparation, and the data contains no individually identifiable information (and cannot be linked to identifiers), it is no longer considered human subject research, and may be closed. If study activities are limited to data analysis or manuscript preparation and any identifiers exist (and need to be maintained for any reason), the study must maintain HRRC approval until the analysis is complete and the data can be destroyed or all links to identifiers are destroyed. Documentation of the destruction of identifiers must be clearly stated on the HRRC closure report in order for the closure to be approved.
The HRRC or Division of Research Protections may select a study for Quality Improvement review based on the risk of study as assessed during initial or continuing review, adverse events/unanticipated problems or other concerns reported to or learned by the HRRC or SOM Office of Research, Division of Research Protections, or as a result of a not for cause selection for review. Such review is conducted in accordance with the Human Research Quality Improvement Review Procedures.