After Approval — Conducting Human Subject Research

Using liquid chromatography and mass spectrometry instrumentation, Pacific Northwest National Laboratory scientists identified and characterized nearly twice as many proteins in blood serum than previously noted, which provides a greater library of proteins to study for potential use in disease diagnosis.

Investigators and the IRB share in the responsibility for ensuring that the rights and welfare of subjects are fully protected throughout the life of a study.

To initiate their research, investigators must be able to document that:

The protocol and all supporting documents have been fully approved by the IRB.
All primary project staff have completed human subject training.
Subjects will be fully informed and their consent obtained in accordance with the approved protocol.

Once the research is initiated, investigators must:

Comply with the terms and conditions of IRB approval throughout the life of the study, including any requirements for additional monitoring or oversight by the IRB.
Submit the protocol for continuing review as scheduled by the IRB at the time of approval.
Promptly report amendments, modifications or changes to the protocol and new findings.
Promptly report all unanticipated problems and noncompliance to the IRB.
Maintain current certification of human subject training for all primary project staff.
Submit a final report upon completion of the study.

The IRB is responsible for providing continued oversight to ensure that:

Every protocol undergoes substantive, in-depth review at least once a year.
Additional monitoring and oversight is provided where necessary.
Amendments, modifications and changes to the approved protocol are reported and reviewed.
All unanticipated problems and noncompliance are reviewed and reported, as appropriate.
A final report is submitted at completion of the study.
Investigators receive IRB guidance and support in the resolution of issues or unanticipated problems.
Investigators and research staff maintain current certification of human subject training.

Forms and Directions

The SBMS Human Subject site provides the procedures, guidelines and forms principal investigators need to conduct human subject research. The following policies and procedures are used by the IRB to continue their oversight of protocols following initial approval:

Continuing Review
Amendments, Modifications, Changes and New Findings
Unanticipated Problems and Noncompliance
Additional Monitoring and Oversight of Approved Protocols
Suspension or Termination of Previously Approved Protocols
Study Completion

See the Information Provided to IRB Members For Review sheet which lists the documents that are required for conducting the reviews contained in this section.

Please note that the IRB uses the procedures found in the "IRB Review and Approval" section for continuing review and review of modifications, including the Primary Reviewer System. General information and procedures for continuing review and for review of modifications are provided below.

Continuing Review

Federal regulations require substantive and meaningful continuing review of active human subject research protocols by the IRB at intervals appropriate to the degree of risk, but not less than once a year and has the authority to observe or have a third party observe the consent process and the research [45 CFR 46.109(e)]. The criteria for approval are the same as that for initial review (see Basic Requirements for Approval) and the requirements of 45 CFR 46 must be fulfilled.

Continuing review is conducted at the same level as initial review and is subject to the same regulations, policies and procedures, including those for IRB membership (quorum) [45 CFR 46.107]. Generally, if research did not qualify for expedited review at the time of initial review, it does not qualify for expedited review at the time of continuing review, except in limited circumstances as described by expedited review categories (8) and (9).

Under review Category (8) of 45 CFR 46.110(b) (1), expedited procedures may be used for continuing review of research previously approved by the convened IRB where:

(i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research–related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or
Where no subjects have been enrolled and no additional risks have been identified; or
Where the remaining research activities are related to data analysis.

Under Category (9) of 45 CFR 46.110, expedited procedures may be used for continuing review of research not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (8) 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. See Categories of Research that May Be Reviewed by the IRB through an Expedited Procedure (.pdf 33kb) for more detailed information. The PNNL IRB would not allow expedited review of any research involving vulnerable subjects, if that research were ever to be conducted.

Categories (8) and (9) cannot be used if:

The remaining procedures are more than minimal risk (not required for (8)(b)).
Identification of the participants or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the participants' financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are not greater than minimal (not required for category (8)(b)).
The research is classified.

It is also possible that research activities that previously qualified for expedited review have changed or will change, such that expedited review would no longer be permitted for continuing review. Also, the IRB would not approve a protocol submitted for continuing review if, due to interim changes in IRB policies and procedures, it would not have approved the protocol as a new study.

The IRB approval for protocols not approved before the original due date are considered expired and out of compliance with the terms and conditions of IRB approval. All activities involving subjects must stop until the protocol has been appropriately reinstated, unless the IRB determines that it is in the best interest of subjects to continue their participation. Enrollment of new subjects cannot occur after the expiration date. Retroactive approval is not allowed under any circumstances.

Continuing Review Procedures

Step 1:

Investigators submit a Continuing Review application at least 1 month before the expiration date for protocols to be reviewed by the full board; 2 weeks for expedited protocols; and 1 week for exempt protocols.

Full Board and Expedited Continuing Review requires that investigators provide a complete package to the IRB, including the Application for Continuing Review (.doc). Procedures for Full Board and Continuing Review found in “IRB Review and Approval" are followed.The PR and the IRB use the "IRB Decision Quadrant and Informed Consent Checklist" (.pdf 161kb) to conduct full board and Expedited continuing review.

Investigators are required to report:

Number of subjects accrued during the last report period.
Number of subjects withdrawn and reason for withdrawal.
Any new information that might affect a subject's willingness to continue his/her participation.
Change in funding or project management.
Any amendments or modifications that took place during the last review period.
Significant new findings, recent publications or press releases.
Summary of unanticipated problems, noncompliance, or complaints reported during the last period.
Recent literature or any other relevant information, especially about research related risks.

Exempt Continuing Review (a PNNL requirement) requires that investigators complete an Application for Continuing Review (.doc) form. Exempt continuing review is conducted to establish that the protocol is still active and maintains its exempt status.

Investigators report:

Current status - Active/Completed
Changes to the approved protocol
Expected changes to the protocol
Expected end date

Step 2:

Follow procedures found in "IRB Review and Approval."

Amendments, Modifications, Changes and New Findings

Any new findings or amendments, modifications, or changes or new findings, must be reported immediately and approved by the IRB before any work impacted by the changes or findings may be initiated – except when necessary to eliminate apparent hazards to subjects or others, and then must be reported within 5 days of the occurrence to the IRB. Possible changes might include, but are not limited to:

Change in research procedures that might impact the type and/or level of risk (unless the change is necessary to eliminate an apparent immediate hazard to the subjects, and then must be reported as soon as possible).
Personnel or job assignments that impact the protocol or alter contact with subjects.
Subject population and/or number of subjects involved.
Type of specimen or data, method for obtaining and identifying the information.
Minor changes to protocols previously reviewed by the convened IRB may be reviewed under the expedited review procedure, subject to consultation with the IRB.
Reports that indicate an increased risk to participants

Expedited review procedures may also be used to review minor changes to protocols that were initially approved by the convened IRB [45 CFR 46.110(b) (2)]. Minor changes are defined as "those which do not involve an increase in risk that is more than minimal, do not change the risk potential benefit relationship of the study, and in which all added procedures fall into categories (1)-(7) of research that can be reviewed using the expedited procedure."

Actions outside the IRB approved scope of research must not be taken without prior IRB approval, except under emergency conditions. An emergency exists only when a human subject is confronted by an exceptionally serious or life-threatening situation and when no standard, alternate, or acceptable treatment is available. In such a situation, the PI must report to the IRB as soon as possible that the conditions exist.

Procedures for Amendments, Modifications, Changes and New Findings

Step 1:

Investigators submit the Protocol Modifications, Amendments, Changes, and New Findings (.doc) form and attach all relevant information in support of the application. See the IRB Documentation Requirements Information Sheet for information provided to the IRB members for review of protocol modifications, amendments and changes.

Full Board Review requires that investigators provide a complete package to the IRB, including the Application for Protocol Modifications, Change, or New Findings (.doc) and provide a presentation at a convened meeting. The PR and the IRB use the "IRB Decision Quadrant and Informed Consent Checklist" (.pdf 161kb). If reviewed by the convened IRB, the review will proceed in the same manner as that used for full board review.

Expedited Review requires that investigators provide a complete package to the IRB, including an Application for Protocol Modifications, Change, or New Findings (.doc). The IRB PM and the PR review the application and the original application. The PR and the IRB use the "IRB Decision Quadrant and Informed Consent Checklist" (.pdf 161kb). If initially reviewed under expedited procedures and nothing has occurred to change that determination, IRB review will proceed in the same manner as that used for expedited review.

Exempt Review (a PNNL requirement) requires that investigators complete an Application for Protocol Modifications, Change, or New Findings (.doc) form. If the changes or new findings increase the level of risk, as determined by the IRB PM, the protocol will be reviewed under expedited procedures. If not, the report will be reviewed and recorded by the IRB PM.

Step 2:

Follow procedures found in "IRB Review and Approval."

Additional Monitoring and Oversight of Approved Protocols

Federal regulations authorize the IRB to monitor human subject research to ensure that protection of human subjects is implemented and enforced. Continuing review is one monitoring tool. Another is to have the IRB or a third-party observe the research, particularly the consent process [45 CFR 46.109(e)].

The underlying purpose for additional monitoring and oversight of a protocol is to assess the general approach, attitude and priority toward the protection of human subjects. Observing the consent process and auditing records, for instance, should indicate how well an investigator and project staff understand and implement their individual responsibilities for protecting the rights and welfare of research subjects.

The IRB may determine that additional monitoring and oversight is required during initial approval or at any other time during the conduct of the study. Refer to IRB Review and Approval for procedures related to this requirement: Determining the Frequency of Review and Additional Monitoring or Oversight.

Policies and procedures to perform monitoring and oversight are contained in the "Project Compliance Review Plan and Check List" (.doc), which explains the method for determining which projects require additional review and provides the procedures used to conduct the review and report the findings.

Reporting Problems, Unanticipated Problems, Noncompliance, and Allegations of Noncompliance

Federal regulation [45 CFR 46.103(b)(5)(i)] requires the organization to have written procedures that ensure prompt reporting to the IRB, appropriate institutional officials, and the Department or Agency head of (i) any unanticipated problems involving risks to subjects or to others or any noncompliance or allegation of noncompliance with the regulations or the requirements or determinations of the IRB; and (ii) any suspension or termination of IRB approval. Investigators should contact the IRB if they are unsure of when to report a problem, unanticipated problem, noncompliance or allegation of noncompliance. The definition for an Unanticipated Problem is located at the bottom of this section.

Reporting Problems and Unanticipated Problems

Investigators are responsible for immediately reporting the following problems that occur during the study, after subject withdrawal or after the study has concluded to the IRB for review. Problems include incidents, experiences, outcomes and new information. Reported problems and unanticipated problems are reviewed by the IRB using the procedures found below. Investigators use the Problems and Noncompliance Report Form (HS-8) (.doc) and guidance in SBMS to report problems and unanticipated problems.

Reportable Problems

Any harm experienced by a subject or by others involved in the study that was not previously identified in the protocol.
New information that alters or changes the risk/benefit ratio.
Breaches of confidentiality. Misuse of private information or records.
Protocol change without IRB review to eliminate apparent immediate hazards to subjects.
Incarceration of a subject in a protocol not approved to enroll prisoners.
Any problem that requires reporting according to the protocol or the sponsor.
Publication in the literature, safety monitoring report, interim result, or other finding that indicates an unexpected change to the risks or potential benefits of the research
Complaints by a subject or a subject’s representative that indicate unexpected risks or that cannot be resolved by the research team.
Protocol violation (meaning an accidental or unintentional change to the IRB-approved protocol) that harmed subjects or others or that indicates subjects or others might be at increased risk of harm.

IRB Procedures for Reviewing Problems and Unanticipated Problems

Please note that a principal investigator's (PI) first responsibility is to secure the safety and well being of the subjects. The PI is authorized to take whatever steps are necessary to eliminate apparent immediate harm to subjects or to others.

Step 1:	The PI immediately notifies the IRB and provides regular status reports as the situation unfolds, particularly in regard to the subject's condition, if applicable.
Step 2:	The IRB Administrative Team and the PI perform an initial assessment to determine if the situation warrants an immediate suspension of IRB approval, pending receipt of further information.
Step 3:	Within no less than 5 days of the initial notification, the PI submits a Problem and Noncompliance Report (HS-8), the approved protocol, consent and all supporting documents to the IRB.
Step 4:	The IRB Administrative Team reviews the report. The IRB Administrative Team may gather additional information or consult with the PI, line management, or others to make their determination.
Step 5:	If the IRB Administrative Team determines that: A) the reported problem was not unanticipated or B) subjects or others are not at an increased risk of harm, the PI is notified that the report is not considered an unanticipated problem and that no further action is required. A) the reported problem was unanticipated and B) any increase in risk of harm to subjects or others is minimal, the report is reviewed by the IRB Administrative Team using the following steps. A) the reported problem was unanticipated and, B) represents more than minimal increased risks to subjects or others, the report is forwarded to the convened IRB and the remaining steps of this procedure are followed.
Step 6:	IRB members (or IRB Administrative Team) are provided with the Problems and Noncompliance Report, the approved protocol, consent and all supporting documents at least one week in advance of the meeting. The PI or others may be invited to the meeting but will be asked to leave the room during IRB deliberations and vote.
Step7:	The IRB (or IRB Administrative Team) considers the following actions: Accept the report with no changes. Accept the report with changes. Require further modification of the protocol, consent or other documents. Require modification of the information disclosed during the consent process. Provide additional information to past participants. Notify current subjects when such information might impact their willingness to continue participation in the research. Re-consent current subjects. Modify the continuing review schedule. Monitor the research or consent process. Refer to other organizational entities. Suspend or terminate the research.
Step 8:	The IRB Chair reports the IRB's findings to the PI, including any further requirements for approval. If approved, the report will so state.
Step 9:	If additional information is required to close out the report, the convened IRB may authorize the IRB Administrative Team to approve minor changes to the protocol, consent or supporting documents. Changes that substantially alter the protocol, consent or supporting documents or increase the risk to subjects or others must be reviewed by the convened IRB.
Step 10:	When all required information is approved by the IRB or IRB Administrative Team, the IRB Chair will issue a final report to all stakeholders in accordance with procedures found in "Reporting Unanticipated Problems, Noncompliance, Suspensions and Terminations." All correspondence related to the review is documented to the project file and in the IRB minutes as appropriate.

Unanticipated problems involving risks to participants or others mean any problem that is:

Unanticipated; and
Indicates that participants or others are at increased risk of harm.

Noncompliance and Allegations of Noncompliance

Investigators are required to report noncompliance and alleged noncompliance to the IRB immediately upon discovery. Any staff member that knows of or suspects noncompliance is responsible for reporting it to the IRB Chair or any member of the IRB Administrative Team. PIs use the guidance found in SBMS and IRB Form HS-8 to report noncompliance or allegations of noncompliance. The IRB uses the policies and procedures below to review and manage noncompliance and allegations of noncompliance.

Noncompliance is a failure to comply with regulations, policies and procedures governing human subject research or the requirements and determinations of the IRB. Examples of noncompliance include the failure to conduct research in accordance with the IRB-approved protocol or failure to obtain approval for continuation of the protocol before the IRB expiration date.

Allegations of Noncompliance are considered unproved assertions of noncompliance until determined otherwise by the IRB Administrative Team.

Once reported, the IRB Administrative Team will determine if the noncompliance or allegation of noncompliance is serious and/or continuing and should be reviewed by the convened IRB and reported as such.

Serious Noncompliance is any action or omission that any reasonable person would foresee as compromising the rights and welfare of human subjects.
Continuing Noncompliance is a pattern of actions or omissions that indicates a deficiency in the ability or willingness of an individual to comply with the federal regulations, HRRP policies and procedures, or the determinations or requirements of the IRB.

Procedures for Reviewing Noncompliance and Allegations of Noncompliance

Step 1:	The PI reporting noncompliance or person reporting an allegation of noncompliance immediately notifies the IRB by phone, fax, e-mail, or in person.
Step 2:	The IRB Administrative Team performs an initial assessment to determine if the situation warrants an immediate suspension of IRB approval, pending further information. If reviewed by the IRB Administrative Team under emergency conditions, the IRB Administrative Team is provided with the approved protocol, consent and all supporting documents.
Step 3:	Within no more than 5 days of the initial notification, the PI or person reporting the noncompliance submits a Problems and Noncompliance Report form (.doc), approved protocol, consent and other supporting documentation to the IRB.
Step 4:	The IRB Administrative Team reviews the report to determine if: The noncompliance is serious or continuing. The alleged noncompliance: Has a basis in fact and should be treated as a finding and, if so, Is serious or continuing Further information or a meeting with the PI or person reporting the noncompliance, or others is required.
Step 5:	If the IRB Administrative Team determines there is no credible basis in fact to the alleged noncompliance, the IRB Administrative Team notifies the person providing the report and the issue is closed. If the IRB Administrative Team determines the noncompliance or allegation of noncompliance is neither serious nor continuing, it is managed by the IRB Administrative Team. If the IRB Administrative Team determines the noncompliance or allegation of noncompliance is serious and/or continuing, the report is forwarded to the convened IRB and is reviewed using the following procedures.
Step 6:	When serious and continuing noncompliance is reviewed by the convened IRB, all members are provided with the Problems and Noncompliance Report, the approved protocol, consent and appropriate supporting documents. The PI or person making the allegation of noncompliance may be asked to attend the meeting, but will not be allowed to stay in the room during the discussion or the vote. Possible actions that might be considered include: Suspension or termination of the research. Modification of the protocol. Modification of the information disclosed during the consent process. Providing additional information to past participants. Notification to current subjects when such information might impact to their willingness to continue participation in the research. Re-consent by current subjects. Modification of the continuing review schedule. Monitoring of the research or consent process. Referral to other organizational entities.
Step 7:	The IRB Chair reports the IRB's findings to the PI or person alleging the noncompliance including any further requirements for approval or continuation or the protocol. If approved, the report will so state. The IRB may vote to allow the IRB Administrative Team to approve minor changes required to achieve final approval.
Step 8:	When all required information is approved by the IRB or IRB Administrative Team, the IRB Chair issues a final report to all stakeholders in accordance with procedures found in "Reporting Unanticipated Problems, Noncompliance, Terminations and Suspensions." All correspondence related to the review is documented in the project file and in the IRB minutes as appropriate.

Suspension or Termination of IRB Approval

In accordance with federal regulations 45 CFR 46.113, the IRB has the authority to place administrative hold, suspend or terminate approval of research that:

Is not being conducted in accordance with the terms and conditions of IRB approval (including the requirements for continuing review).
Has been associated with unexpected or serious harm to subjects.

Suspension of IRB approval is "a temporary withdrawal of IRB approval for some or all research procedures or, a permanent withdrawal of approval for some research procedures." Studies that have been suspended still require continuing review. A suspended study may be re-opened after the unanticipated problem triggering the suspension has been resolved.

Termination of IRB approval is defined as "a permanent withdrawal of IRB approval for all research procedures." Terminated protocols are considered closed and no longer require continuing review.

The IRB Chair is designated to suspend or terminate IRB approval on an urgent basis. Any suspensions and terminations made by the IRB Chair on an urgent basis must be reported to and reviewed by the convened IRB. Individuals or bodies other than the convened IRB that suspend or terminate research (for other reasons) must report that action to the IRB for its review.

When study approval is suspended or terminated, the IRB will:

Consider actions that should be taken to protect the rights and welfare of currently enrolled subjects.
Consider whether procedures for withdrawal of enrolled participants considered their rights and welfare.
Consider whether participants should be informed of the termination or suspension.
Require any unanticipated problems or outcomes be reported to the IRB.

Any suspension or termination of IRB approval will be reported promptly to the PI and to their line management via a letter that will clearly describe the action and the reasons for the action taken by the IRB. If issues leading up to the suspension or termination of IRB approval are not resolved within 30 working days, the IO, Battelle Office of Research Administration, the Department or agency head and the research sponsor will be notified, as appropriate and any other necessary action will be determined at that time.

Procedures to Suspend or Terminate IRB-Approved Research:

The IRB or IRB Chair (designee) uses the following procedures to suspend or terminate IRB-approved research.

Step 1:	The IRB (or IRB Chair – designee under urgent circumstances) considers whether any actions need to be implemented immediately to protect the rights and welfare of current participants as described in "Protection of currently enrolled participants" below and orders any actions that need to be taken prior to review by the convened IRB in order to eliminate apparent immediate hazards.
Step 2:	The IRB documents in the IRB record the reasons for the suspension of IRB approval and if applicable, any actions ordered to take place.
Step 3:	The IRB notifies IRB staff of the suspension or termination of IRB approval and actions ordered.
Step 4:	IRB staff communicates the IRB's actions to the investigator.
Step 5:	IRB staff place the suspension or termination of IRB approval on the agenda of the next available IRB meeting. IRB staff distributes to all IRB members a copy of the current protocol, the current consent documents, and any supporting information relevant to the suspension or termination of IRB approval. Whenever possible the IRB designee who ordered the suspension or termination of IRB approval attends the meeting. If the designee cannot attend the meeting, the designee must provide a written report. The IRB votes to continue, reverse or modify the suspension or termination of IRB approval. If the IRB votes to continue or modify the suspension or termination of IRB approval, the procedures in "Suspension or termination of IRB approval by the convened IRB" are followed. The IRB considers whether any actions need to be implemented to protect the rights and welfare of current participants and votes on the actions to be taken. The IRB documents in the IRB minutes the reasons for the suspension or termination of IRB approval and if applicable, any actions ordered to take place.
Step 6:	All suspensions and terminations are reported in accordance with the procedures found in "Reporting Problems, Unanticipated Problems, Noncompliance, Terminations and Suspensions." All correspondence related to the review will be documented in the project file.

Administrative Hold

An administrative hold is a voluntary action by an investigator to temporarily or permanently stop some or all approved research activities in response to a request by the convened IRB or IRB designee to take such action. Administrative holds are not suspensions or terminations and are not subject to the same reporting requirements. An administrative hold may be placed when an investigator is unable to complete continuing review on the due date.

Procedures for Placing an Administrative Hold

The convened IRB or IRB designee may request that an investigator place a research study on administrative hold by the following procedures:

Step 1:	The IRB or person requesting the administrative hold in consultation with the investigators determines whether any additional procedures need to be followed to protect the rights and welfare of currently enrolled participants.
Step 2:	The IRB or person requesting the administrative hold, in consultation with the investigators, determine how and when currently enrolled participants will be notified of the administrative hold.
Step 3:	Investigators must notify the IRB in writing that: They are voluntarily placing a study on administrative hold in response to a request by the convened IRB or IRB designee. A description of the research activities that will be stopped. Proposed actions to be taken to protect current participants. Actions that will be taken prior to IRB approval of proposed changes in order to eliminate apparent immediate harm.
Step 4:	Upon receipt of written notification of the investigator the IRB staff places the research on the agenda for IRB review.
Step 5:	Investigators may request a modification of the administrative hold by submitting a request for a modification to previously approved research.

Reporting Unanticipated Problems, Serious and Continuing Non-Compliance, and Suspensions and Terminations to Regulatory Agencies and Institutional Officials

Note: See the section on “Accreditation” for all AAHRPP reporting requirements.

The policy for reporting unanticipated problems, serious and continuing non-compliance, and suspensions or terminations is invoked whenever:

A unanticipated problem is determined to involve risks to participants or others.
Non-compliance is determined to be serious or continuing.
The IRB or the organization suspends or terminates IRB approval of research.

Step 1:	The IRB Program manager will prepare the report which will contain: The nature and type of event Name of the institution conducting the research. Title of the research project and/or grant proposal in which the unanticipated problem occurred. Name of the principal investigator on the protocol. Name of the person who reported the incident or initiated the action. Number of the research project assigned by the IRB and the number of any applicable federal award(s) (grant, contract, or cooperative agreement). A detailed description of the unanticipated problem including the findings of the organization and the reasons for the IRB's decision. Actions the institution is taking or plans to take to address the unanticipated problem (e.g., revise the protocol, suspend subject enrollment, terminate the research, revise the informed consent document, inform enrolled subjects, increase monitoring of subjects, etc.). Plans, if any, to send a follow-up or final report by the earlier of: A specific date. When an investigation has been completed or a corrective action plan has been implemented.
Step 2:	The Chair will approve and sign the report.
Step 3:	The report will be sent to: The IRB The Signatory Official of the Battelle Federalwide Assurance Director of the Pacific Northwest National Laboratory/Institutional Official The following agencies: (reporting is not required if the agency has been notified of the event by other mechanism or by another site.) OHRP DOE Office of Human Research Protection Any other Common Rule agency involved in the conduct, support, or oversight of the research when that agency requires reporting separate from reporting to OHRP FDA, if the research is FDA-related Principal investigator. Study sponsor. Contract research organization, if the study is overseen by a contract research organization. Direct manager of the principal investigator.
Step 4:	Reporting of the event, under normal circumstances should be no more than 30 day from the time the incident is reported to the IRB. For more serious actions, the IRB manager will expedite reporting as much as possible.

Study Completion

When a study is completed or terminated before completion, the investigator is required to submit a final report (.doc) to the IRB. A copy of any summary reports and final publications must be provided with the report, which will be distributed to the IRB and the project file. The project completion will be documented in the IRB database and the file will be closed.