Principal Investigator Manual

IRB Required Reports

The UCF Protocol Application Form is required to submit a new study to the IRB for initial review. Once a study has been approved, federal regulations require that the principal investigator keep the IRB informed of the progress of the study, new information learned, complaints from participants or others, changes to be made, deviations from the protocol, and adverse events or unanticipated problems.

Addendum/Modification Request Form-To Request Changes

When protocol or study changes are proposed, a written description of the proposed changes to the protocol, informed consent process and/or research instruments must be submitted to the IRB office using the Addendum/Modification Request Form within the iRIST system for review and approval prior to implementation. Only in the rare circumstance when it is necessary to eliminate apparent immediate hazards to the research participants, as noted in federal regulations, is a researcher permitted to modify an approved protocol without the prior review and approval of the IRB. In this case, the IRB must be informed within five (5) days of the change following its implementation. The change will be reviewed to determine that it is consistent with protection of human participants regulations. Minor modifications proposed for previously approved protocols (e.g., number of participants, venue of the data collection, the addition or removal of key study personnel, etc.) must be reviewed by the IRB chair or other designated reviewer and may be done by expedited review regardless of whether the study was initially reviewed and approved by expedited or full board review. If the study was initially approved by the full board at a convened meeting, major modifications must be reviewed by the full board at a convened meeting.

Serious Adverse Event Report Form

An adverse event is an undesirable and unintended incident which may affect the safety of research participants or others. Adverse events which are not serious, unanticipated and related or possibly related do not have to be reported to the IRB as a serious adverse event except in the case of a death which should be reported regardless of cause. In medical research an unanticipated adverse event is one that was not described in the protocol or the investigator's brochure and, therefore, was not listed in the consent form. Events which are related or possibly related are those in which there is a reasonable possibility the adverse event may have been caused by the experimental intervention portion of the study, the drug or the medical device. The principal investigator should report the serious adverse event, explain if there is not enough information to determine if it is related, and note if additional information will be forthcoming after investigation.

The principal investigator is responsible for reporting serious adverse events to the IRB using the Serious Adverse Event Report Form within the iRIST system within 5 working days of gaining knowledge of the event. The form requires that the PI state whether the adverse event is internal or external. Serious adverse events which occur at sites other than UCF in large multicenter drug trials with multiple sites should be reported to the IRB when the Data Safety and Monitoring Board (DSMB) has determined that changes should be made to the consent form or that participants should be reconsented to advise them of increased risks. If the adverse event occurs at one of the local hospitals in a study that has been reviewed by both IRBs, the principal investigator should first report the serious adverse event to the hospital IRB and secondly report it to the IRB.

A serious adverse event is described as one or more of the following:

• Results in death, or
• is life threatening, or
• requires inpatient hospitalization or prolongation of existing hospitalization, or
• results in serious, persistent, or significant disability or incapacity, or
• results in a congenital anomaly or birth defect, or
• is an overdose, or
• is any medical event which requires treatment to prevent one of the medical outcomes listed previously (based on 21 CFR 312.32(a).

OHRP requires investigators to report serious adverse events promptly (within 5 working days) and in writing to the IRB. The principal investigator must provide a description of the adverse event and state whether or not changes are needed in the protocol and the informed consent process, and whether or not research participants must be notified regarding the event. These revisions must be reviewed by the full board. If the events are deemed to place participants at increased risk, the chair may temporarily stop the research and suspend additional enrollment until the full board has reviewed the serious adverse event report at a convened meeting. In a circumstance in which the board perceives that the research participants may be placed at significant risk or the research is not being conducted in accordance with the IRB's requirements , the IRB has the authority to suspend or terminate approval of a protocol, 45 CFR 46.113, requiring at a minimum the immediate cessation of data collection from research participants. Any such action shall include a statement of the reasons for the IRB action, and the chair will contact the appropriate university officials, sponsors, and/or OHRP as required in the Federalwide Assurance agreement with OHRP. Investigators may view OHRP updated information dated January 15, 2007 entitled, "Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events" on the OHRP Web site at http://www.hhs.gov/ohrp/policy/AdvEvntGuid.htm for additional clarification and samples.

Unanticipated Problem/Notable Event Report Form

The IRB, per federal regulations, also requires that unanticipated problems involving risk to research participants or others be reported to the IRB in a timely manner. An example of a reportable unanticipated risk to others would be a research technician being inadvertently exposed to a low level of radiation during a study. It is not necessary that a participant has been harmed for the problem to be reportable, but that the potential for harm has increased. For example, a reportable unanticipated problem would be an incident where a laptop computer which contained identifiable information for participants was stolen. It is not necessary that someone's identity be stolen or the information be used fraudulently, only that it was taken and could be used for such purposes. Report unanticipated problems that do not fit the description of an serious adverse event to the IRB using the Unanticipated Problem Report Form within iRIST. This form should also be used by a PI to report a complaint that he/she has received regarding the study. Investigators may view OHRP updated information dated January 15, 2007 entitled, "Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events" on the OHRP Web site at http://www.hhs.gov/ohrp/policy/AdvEvntGuid.htm for additional clarification and samples.

Protocol Violation Reporting Form-To Report a Deviation from Protocol

In clinical trials a protocol which details the formal design or plan of an experiment or research activity; specifically, the plan submitted to an IRB for review and to an agency for research support.

The protocol includes a description of the research design or methodology to be employed, the eligibility requirements for prospective subjects and controls, the treatment regimens, the proposed methods of analysis, the data management and monitoring plan, confidentiality protections and expected side effects. A protocol violation is any exception or deviation involving a single subject that is not approved by the IRB prior to its initiation or implementation. These protocol violations may be major or minor violations. A major violation is one that may impact subject safety, make a substantial alteration to risks to subjects, or any factor determined by IRB chair or IRB member as warranting review of the violation by the convened IRB. Examples of major violations may include:

• Failure to obtain informed consent, i.e., there is no documentation of informed consent, or informed consent is obtained after initiation of study procedures;
• Enrollment of a subject who did not meet all inclusion/exclusion criteria;
• Performing study procedure not approved by the IRB;
• Failure to report serious unanticipated problems/adverse events involving risks to subjects to the IRB and (if applicable), to the sponsor;
• Failure to perform a required lab test that, in the opinion of the PI, may affect subject safety or data integrity;
• Drug/study medication dispensing or dosing error;
• Study visit conducted outside of required time frame that, in the opinion of the PI or IRB, may affect subject safety;
• Failure to follow safety monitoring plan.

A minor violation is one that does not impact subject safety or does not substantially alter risks to subjects. Examples of minor violations may include, but are not limited to:

• Implementation of unapproved recruitment procedures;
• Missing original signed and dated consent form (only a photocopy available);
• Missing pages of executed consent form;
• Inappropriate documentation of informed consent, including:
  

a. Missing subject signature;
b. Missing investigator signature;
c. Copy not given to the person signing the form;
d. Someone other than the subject dated the consent form;
e. Individual obtaining informed consent not listed on the IRB approved study personnel list.

• Use of invalid consent form, i.e., consent form without IRB approval stamp or outdated or expired consent form;
• Failure to follow the approved study procedure that, in the opinion of the PI, does not affect subject safety or data integrity including:

a. Study procedure conducted out of sequence;
b. Omitting an approved portion of the protocol;
c. Failure to perform a required lab test;
d. Missing lab results;
e. Enrollment of ineligible subject (e.g., subject's age was 6 months above age limit);
f. Study visit conducted outside of required timeframe.
g. Over-enrollment beyond what was approved by the IRB;
h. Enrollment of subjects after IRB-approval of study expired or lapsed;
i. Failure to submit continuing review application to the IRB before study expiration.

If either a protocol deviation or protocol exception occurs without prior IRB review and approval, the principal investigator is responsible for completing a Protocol Violation Reporting Form within fourteen (14) days of the occurrence and submitting it to the IRB for review within iRIST . If applicable, the principal investigator is responsible for reporting protocol violations to the sponsor, and/or FDA.

Continuing Review Form-To Renew a Study

Projects are re-reviewed when the use of human participants is expected to continue beyond the original IRB approval period. All protocols approved by the IRB are subject to continuing review at intervals appropriate to the degree of risk, but not less than once in the twelve (12) months following approval. The iRIST system will automatically send out four e-mail notifications starting forty-five (45) days prior to the study expiration date. The principal investigator is ultimately responsible for submitting the Continuing Review Form through the iRIST system regardless of whether he/she received the e-mail notification. It is the principal investigator's responsibility to notify the IRB office if his/her e-mail address changes so that the iRIST system user account can be updated. If a study was approved by full board review initially, the Continuing Review Form should be submitted within iRIST about sixty (60) days prior to expiration in order to have it pre-reviewed and added to the meeting agenda in a timely manner so that the study does not expire. In some situations a study that was approved by full board review may be renewed by expedited review (see the two situations below). The allowable 365 day approval period starts with the date of the meeting at which contingent approval was granted, not the date the final approval was granted after corrections were made. This is mandated by federal regulations. The IRB has the option of approving a study for a shorter time period if it determines that this is warranted because of risk or other issues. The approval letter will state the expiration date. Investigators should continue to submit the Continuing Review form and renew the study until data analysis has ended.

If the IRB approval of a study expires before the renewal process is complete, study enrollment is suspended and the status will be marked "expired". While suspended, no new participants may be enrolled. Interactions with participants, including but not limited to surveys and focus group meetings, must stop. Interventions under the research protocol must be halted except when over-riding concerns for the safety or well being of the subjects, or other ethical issues, are involved. In such cases, the investigator must contact the IRB immediately if there is a need to continue study medications or other procedures to protect subjects. The IRB chair will make a determination whether or not the study medications or other procedures shall proceed. The suspension will be lifted if the study is re-approved by the IRB. The principal investigator should contact the IRB office if a study has expired and it needs to be re-opened. The approval letter will note the lapse in IRB approval and will generally state that any data collected during the time period may not be used and should be destroyed. The IRB chair may make a determination to allow the use of the data in extenuating circumstances. Collection of data after notification that the study has been suspended or expired to constitutes noncompliance with the federal regulations. If the IRB has not re-approved the protocol before the expiration date, approval expires and data collection must cease. The board and the institutional officials will be notified of the expiration or suspension. If the IRB office determines that a new protocol application submission form is be required within the iRIST system, the PI should note that it is a resubmission and give the IRB number it replaces. No two titles of studies should be the same, therefore, add a roman numeral "II" at the end of the title.

It is the principal investigator's responsibility to apply for renewal before the expiration date allowing a minimum of three (3) weeks for review if the study can be reviewed by expedited review. E-mail notifications will automatically be sent to the PI through iRIST starting at forty-five (45) days before the continuing review due date. Researchers have the responsibility to submit the Continuing Review Form in a timely manner to ensure enough time to make requested changes so that IRB approval does not expire. An updated consent form must be uploaded and submitted with the Continuing Review Form so that it can be stamped with the new expiration date. Changes to the study may be requested by the PI at the time of continuing review instead of submitting an Addendum/Modification Request Form at the same time, but it must be clear from the description what was previously approved and what change is being requested. If a pharmaceutical company sponsored study addendum is being submitted, it must be submitted separately with the Addendum/Modification Request Form as required by the sponsor for tracking purposes. Any changes to the protocol that need to be made throughout the year, must be submitted via submission of the Addendum/Modification Request Form within the iRIST system at the time the change is needed as it must be approved prior to implementation. If the IRB has not re-approved the study before the expiration date, approval expires and data collection must cease. The board and the institutional officials will be notified of the expiration as well as the funding source, in some situations, which could jeopardize funding.

The principal investigator will receive e-mail notification to log into iRIS when the approval process is complete. The approval letter will be available for printing within the iRIST system.

If the study was approved initially by full board review, and the IRB did not state in its minutes for the meeting that an expedited continuing review will be allowed in the future, the principal investigator must submit the Continuing Review Form sixty (60) days before the continuing review due date in order to allow time to put the study on the IRB meeting agenda for full board review. Expedited review and approval is allowable for continuing review even if a study was initially approved by full board review when one of the two following situations exist and, if applicable, the PI may submit the form 2-3 weeks before the continuing review date:

• Continuing review of research previously approved by the convened IRB as follows:

a. Where
      the research is permanently closed to the enrollment of new subjects;
      all subjects have completed all research-related interventions; and
      the research remains active only for long-term follow-up of subjects; or

b. Where no subjects have been enrolled and no additional risks have been identified; or

c. Where the remaining research activities are limited to data analysis.

• Continuing review of research, not conducted under an investigational new drug application or investigational device exemption where expedite categories two (2) through (8) noted in the previous section do not apply, but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

Termination/Final Report Form-To Terminate a Study

The principal investigator is responsible for notifying the IRB of changes to the research including completion of the research. If there is a funding source, the IRB approval for the study should remain in force until the account has been closed out. It is best to keep the IRB in force until the analysis is finished or there are no longer any identifiers because the IRB is responsible for the oversight of the confidentiality issues. By notifying the IRB through use of the Termination/Final Report Form within iRIST, the IRB's database is kept current. Technically per federal regulations, exempt studies do not require a termination report, but the IRB requests that investigators submit the report so that there are no misconceptions about which research studies are still being conducted on campus.

If a graduate student or a faculty member is the principal investigator and he/she leaves UCF, it is his/her responsibility to submit an Addendum/Modification Request form appointing someone else as principal investigator if the study is to continue at UCF or a Termination/Final Report form if the study is complete. A faculty advisor listed on the study will be able to submit a Continuing Review or Termination/Final Report form. A person listed only as a "contact" will receive all the e-mail notifications but will not be able to submit a Continuing Review or Termination/Final Report form. That person must be added manually as a Faculty Advisor or co-PI by the IRB staff in order to have the ability to submit for that particular study. There have been some problems in this area due to the migrated studies that were already active when the IRB converted to the electronic iRIST system. Contact the IRB office for assistance as needed. Investigators should not just ignore the notifications because he/she will continue to receive them multiple times.

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