IRB Review and Approval

Research involving human subject-related activities must be reviewed by the IRB at the following times

Before research activities may be initiated
Before changes to the approved protocol may be initiated
At the time of continuing review
When problems or Noncompliance are reported

This section provides IRB policies and procedures for reviewing human subject research. See the PNNL Human Subject Review Process (.pdf 89kb) for a description of the process. Detailed procedures and forms for investigators are provided in SBMS Human Subject Research.

IRB review may be delayed until project funding is assured but must be completed prior to the initiation of any human subject activity. PIs should be aware that some clients, such as the National Institute of Health, require documentation of IRB approval to conduct scientific review or authorize funding and should plan accordingly.

Evaluating Human Exposure to Volatile Organic Compounds in Residential Water

Proposal Development

PIs are encouraged to consult with the IRB early in the development of their proposals to ensure that: 1) their studies are scientifically sound (worthy of involving human subjects); 2) the rights and welfare of subjects are fully considered in the study design, and 3) the study has a high likelihood of meeting the criteria for IRB approval. Sections, "Selecting, Recruiting and Consenting Subjects" and "Items for Consideration" in this website provide guidance on good research design. Early planning is also beneficial when dealing with complicated protocols, collaborative research, or foreign countries where multiple IRB reviews may be required. It is also helpful when a protocol needs to be initiated immediately upon receipt of funding.

In general, based on an assessment of the risks and benefits, complexity of the protocol, and quality and completeness of the information provided, IRB review may be accomplished in as little as a day for exempt protocols or from 4-8 weeks for full board review.

Initiating IRB Review

PIs are responsible for notifying the IRB of their intent to conduct human subject research and may do so either by personal contact or through the Electronic Prep and Risk (EPR) or Environmental Molecular Science Laboratory (EMSL) proposal systems. The IRB PM works with the DOE PNSO Office, ES&H, the PNNL Materials Transfer Agreement Office and the Institutional Biosafety Committee to identify human subject activities.

Criteria for IRB Approval of Research [45CFR 46.111]

To approve research involving human subjects, the IRB must confirm that the following are accomplished.

Risks to subjects are minimized
Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.
The selection of subjects is equitable.
Informed consent will be sought from each prospective subject or the subject's legally authorized representative.
When appropriate, there are adequate protections to protect the privacy of subjects and to maintain the confidentiality of data.
When some or all of the subjects are likely to be vulnerable to coercion or undue influence, additional safeguards have been included in the study to protect their rights and welfare. Note: PNNL does not currently conduct research using vulnerable subjects. Formal policies must be established by the IRB before activities involving these subjects can be reviewed or conducted.

Levels of IRB Review

Federal regulations allow for three levels of review: Exempt Expedited and Full Board. While the requirements of 45 CFR 46 and many underlying issues must be considered. The appropriate level of review is generally based on the nature and magnitude of risk posed by the research.

At PNNL, the IRB Administrative Team determines the appropriate level of review. To establish the appropriate level of review, the IRB Administrative Team uses the OHRP Human Subject Regulations Decision Charts 2 through 9, the IRB Decision Quadrant and Informed Consent Checklist (.pdf 161kb), and the application package submitted by investigators.

At any time during the course of a study, the IRB may change the level of review if it determines that oversight is warranted, risks to subjects or to others has increased, or the assigned level of review is no longer appropriate. PNNL requires that studies qualifying as exempt must be reviewed on an annual basis and tracked to completion in much the same manner as full board and expedited studies.

Procedures for Conducting Exempt, Expedited and Full Board Review

1. Exempt Review

Certain research activities are considered exempt from rigorous IRB review when they meet one or more of the categories of exemption as stated in the Federal criteria for exemption (.pdf 56kb) [45 CFR 46.101], as determined by the IRB. Note that the PI cannot make this determination themselves. At PNNL, the IRB determines which studies qualify for exemption.

A determination of exemption does not necessarily preclude the need for consent, or other supporting documentation such as IRB review from collaborating institutions. Research that has been determined to be exempt must be conducted according to the principals in the Belmont Report and professional principles and standards such as those adhered to by the Oral History Society

To initiate an exempt review, the PI must complete the "Request for Administrative Review form and submit it to the IRB.

Exempt Review Procedures

Step 1:	The investigator contacts the IRB PM and submits the appropriate "Request for Administrative Review" form and appropriate supporting documentation as noted in the "Information Provided to IRB Members for Review sheet". Information might include consent or IRB approval from a collaborating institution.
Step 2:	The IRB Administrative Team uses the OHRP Decision Charts 2-7 to determine if the research qualifies for exemption under 45 CFR 46.101 and if so, which exemption applies.
Step 3:	The IRB Administrative Team reviews the application and requests any additional materials required to complete the review. If required, the IRB Chair will determine if additional expertise is required to conduct the review.
Step 4:	If approved, the IRB PM assigns a number to the protocol and documents the exemption to the PI stating the regulation(s) by which the determination was made and providing the expiration date of the IRB approval.
Step 5:	When required, the PI or contract representative documents the exemption to the client. Proposals to DHHS and other federal agencies typically require notification of exemption on the cover page. The IRB will provide an HHS 310 Form to document a review at the PI's request.
Step 6:	Exempt studies are reviewed annually (a PNNL requirement), using the Exempt Continuing Review form (.doc). Final reports are not required for exempt protocols.

2. Expedited Review

Activities that meet the federal definition of "minimal risk" and fit into one or more of the research categories listed in Federal regulation 45 CFR 46.110, Categories of Research that May Be Reviewed by the IRB through an Expedited Procedure (.pdf 33kb) may qualify for expedited review.

Minimal Risk means that "the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests." Special restrictions apply to vulnerable subjects.

Expedited Review may not be used:

Where identification of subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subject's 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 no greater than minimal.
For classified research involving human subjects.

The IRB Administrative Team may approve a protocol, ask for modifications to achieve approval, or refer the protocol to the full board. Proposed research may not be "disapproved" under expedited review but may be referred to the full board for further consideration. Contingent approval is not granted under expedited review.

Expedited Review Procedures

Step 1:	The IRB PM reviews the application for completeness (see "Information Provided to the IRB for Review" sheet), requests additional information, and confers with the IRB Administrative Team to determine if additional expertise is required. The IRB PM helps develop the consent process and other supporting documents such as those required when other institutions or IRBs are involved.
Step 2:	The IRB Chair appoints one or more experienced members of the IRB Administrative Team (those with sufficient prior experience as an IRB member knowledgeable of regulatory requirements for approval) as Primary Reviewers (PR). The IRB Chair may confer with the IRB Administrative Team and, if needed, obtain additional expertise from the IRB or elsewhere (generally within PNNL) to assist the PRs. The PR(s) receive and reviews all materials the convened IRB would have been provided.
Step 3:	If reviewed by more than one PR, consensus is reached by meeting, phone or email and a meeting with the PI may be called by any of the reviewers. Conflicts of interest are addressed throughout the process and disputes are handled in accordance with procedures noted in The Institutional Review Board section of this web site.
Step 4:	The PR(s) review(s) the application package and determine(s) the category under which the protocol will be reviewed using 45 CFR 46.110, Categories of Research that May Be Reviewed by the IRB through an Expedited Procedure (.pdf 33kb), and also uses OHRP Chart 8, "May the IRB Review be Done by Expedited Procedures Under 45 CFR 46.110?" and Chart 9, "Can Continuing Review be Done by Expedited Procedures under 45 CFR 46.110?" in its deliberations.
Step 5:	The PR uses the IRB Decision Quadrant and Informed Consent Checklist (.pdf 161kb) to review expedited protocols and assess the consent process. If solicited, any information provided by consultants will be included in the documentation, reported to the IRB, and recorded in the minutes and project file. If additional information is needed, the PR will contact the PM or the PI.
Step 6:	If not approved, the PR will confer with the IRB Administrative Team, the IRB PM will document any changes required to achieve full approval to the PI, and the process will repeat.
Step 7:	If the PR determines the protocol and consent process meet the basic requirements for approval [45 CFR 46.111], the PR will recommend the IRB Chair sign the approval.
Step 8:	The IRB PM will provide a Notice of Approval (.pdf) to the PI within 5 days. The notice will document the regulation(s) and conditions under which the approval was granted and the expiration date of IRB approval. The PI will receive copies of the PNNL Human Subject Bill of Rights and Responsibilities (.pdf) and PNNL Principal Investigator Roles and Responsibilities (.pdf). The IRB PM documents approval to sponsors or others, as needed.
Step 9:	The IRB PM documents approval to sponsors or others, as needed and records the approval in the project files and IRB data base.
Step 10:	IRB members are provided with a list of expedited protocols on a monthly basis.

3. Full Board Review

Research activities that do not meet the definition of "minimal risk" must be reviewed by the convened IRB. A legal quorum must be established and conflicts of interest discussed and resolved before review of a protocol may be initiated, including those of any consultants that participate in the review. See "The Institutional Review Board" for additional information regarding requirements for full board review.

Full Board Review Procedures

Step 1:	The IRB PM reviews the application for completeness, (see "Information Provided to the IRB for Review" sheet), requests additional information, and confers with the IRB Administrative Team to determine if additional expertise is required to complete the review.
Step 2:	The IRB Chair appoints a Primary Reviewer (PR) from the IRB members and, if needed, obtains additional expertise from the IRB or elsewhere (generally within PNNL) to assist in the review.
Step 3:	IRB Members and invited consultants are provided with a complete review package at least one week in advance of the convened meeting. Each package includes an IRB Decision Quadrant and Informed Consent Checklist (.pdf 141kb) to assist the IRB in its review and to determine if the basic requirements for approval and consent are met.
Step 3:	The PI meets with the IRB to present and discuss the protocol. The PI leaves the room before final IRB discussion and vote. Consultants may not vote and may be asked to leave the room before the final discussion.
Step 4:	If the protocol and consent process meet the basic Criteria for Approval, the IRB may vote to authorize one of the following: Full Approval: Approved without contingencies. The continuing review schedule, which will be determined during the vote, will commence on the date of approval by the convened IRB. Contingent Approval: Contingent approval requires that minor modifications or additional information be provided by the PI before full approval can be granted. The reasons for contingent approval will be communicated to the PI by email or memo. When substantive clarification or modifications regarding the protocol or consent are required, IRB approval will be deferred until the materials are resubmitted for review by the convened Board. The IRB may authorize the IRB Administrative Team to expedite final approval of specific revisions that require simple concurrence or minor changes. Notification of final approval will be reported to the PI and the IRB. The continuing review schedule, which will be determined during the meeting, will commence on the date contingent approval was originally granted by the convened Board. If the protocol and consent process do not meet the IRB Criteria for Approval, the IRB may vote to authorize one of the following: Table: The IRB may table a protocol that needs major work or lacks sufficient information for the IRB to complete its review. When the IRB tables a protocol, it will document the reasons for doing so to the PI. Until the PI provides the required information and/or revises the materials, the board can take no further action, and no activity may begin on the study. Disapprove: The IRB will specify the reasons for disapproval to give the PI directions and an opportunity to appeal the decision, which must be presented in writing or in person to the IRB Chair. Protocols that are disapproved by the PNNL IRB cannot be submitted to any other IRB and the use of human subjects for the same purpose cannot be approved by any other PNNL entity.
Step 5:	If approved by the convened IRB, the IRB PM issues a Notice of Approval to the PI specifying the regulation(s) and conditions under which approval was granted, including the continuing review schedule and expiration date of approval. The consent form and supporting documents are stamped with the project identifier and expiration date of approval. Copies of the PNNL Bill of Rights and Responsibilities for Human Subjects (.pdf) and PNNL Principal Investigator Roles and Responsibilities (.pdf) are provided to the PI for review and distribution to subjects and project staff.
Step 6:	If not approved by the convened IRB: The IRB may authorize final approval of minor changes to the IRB Administrative Team. The IRB PM will notify the PI of the IRB"s findings and requirements for approval. If the PI responds with the appropriate or revised documents required by the IRB, one of two things will happen: If authorized to do so, The IRB Administrative Team, will review and approve the documentation under expedited review, or The IRB will convene to review the revised documentation and the process will repeat until the IRB has received the documentation it needs to approve the protocol.
Step 8:	The IRB PM documents approval to sponsors or others and records the approval in the IRB minutes, project files and IRB data base. Meeting minutes include information described in "The Institutional Review Board – Meeting Minutes" section of this web site.

Reviewing the Consent Process

The IRB uses the IRB Decision Quadrant and Consent Check List to review the consent process. Refer to "The Informed Consent Process – Selecting, Recruiting, and Consenting Subjects" for guidance.

Step 1:	The IRB PM assists the PI in the development of an appropriate and effective consent process. If collaborating with other institutions responsible for consenting subjects, documentation of that institution"s IRB approval is usually required to complete the application.
Step 2:	For exempt reviews, the consent process is reviewed by the IRB Administrative Team. For expedited reviews the consent process is reviewed by the PR(s). For full board review, the consent process is reviewed by the convened Board. The IRB uses the IRB Decision Quadrant and Informed Consent Checklist (.pdf 161kb) to ensure that the consent process and form meet the criteria for approval.
Step 3:	The IRB PM will notify the PI of any required alterations or changes to the consent process. Changes to exempt or expedited protocols may be approved by the IRB Administrative Team. Changes to full board reviewed studies require approval by the convened IRB or authorization to the IRB Administrative Team by the IRB to expedite the changes.
Note: Draft solicitations, advertisements, audio/video-taped advertisements must be approved in final form before they may be used to solicit subjects. PIs use IRB form HS-6, "Protocol Modifications, Changes or New Findings to submit final copies for IRB review. Note: When reviewing consents from collaborating institutions, the IRB will convey any concerns or questions to the PI who may forward them to the collaborating PI. If serious the PNNL IRB review may be tabled until the concerns are resolved.

Determining the Frequency of Review and Additional Monitoring or Oversight

Continuing Review

Federal regulations require substantive and meaningful continuing review by the IRB at intervals appropriate to the degree of risk but not less than once a year. The IRB establishes the schedule for continuing review when it first approves the protocol. All approval dates originate on the day the protocol was first approved by the IRB even if contingencies are assigned to that approval and the actual start date of the protocol is delayed until those contingencies are met.

The expiration date is the last date the protocol is approved. For example, if originally approved on 10/15/06, the protocol must be approved for continuation by COB 10/14/07.

Continuing review has to occur as long as the research remains active for long-term follow-up of participants, even when the research is permanently closed to enrollment of new participants and all participants have completed all research-related interventions, and it has to occur as long as the research activities are limited to the collection of private identifiable information.

If a request for continuing review is not submitted or approved by the expiration date, research activities involving subjects must cease unless the IRB finds that an over-riding safety or ethical concern is involved such that it may be in the best interest of subjects to continue their participation. However, no new enrollment of subjects may take place until the project is approved for continuation.

PIs that fail to obtain approval before the expiration date of IRB approval are considered out of compliance with the terms and conditions of approval and must appeal for reinstatement. Line management will be notified, as appropriate, when projects are found out of compliance.

The continuing review schedule may be revised (required more often) at anytime during the course of a study if the IRB determines that additional oversight is warranted but, generally, the annual review date remains the same throughout the life of a study, and does not change if submitted than required. For instance, if the IRB approves a study 2 weeks prior to the actual expiration date of 10/15/06, the new review date is still 10/14/07.

Additional Monitoring or Oversight

The IRB has the right to observe or have a 3rd party observe the consent process and the research [45 CFR 46.112]. If a study involves any of the following, the IRB may seek additional monitoring (beyond reports from the PI) to verify that the approved protocol is being followed and that no material changes have occurred since the previous IRB review.

Complex projects involving unusual levels or types of risk to subjects or the use of vulnerable subjects.
PIs that previously failed to comply with the terms and conditions of IRB approval.
Concern that material changes might occur without IRB approval as based on previous experience.

Procedure to Determine the Frequency of Review, Additional Monitoring or Oversight

Annual review is generally considered sufficient for studies involving minimal risk. For those determined by the IRB to involve more than minimal risk, or where additional monitoring or oversight may be required, the following procedure is invoked.

Step 1:	The IRB Administrative Team or convened IRB determines potential risks: nature (physical, psychological, social, economic) severity (moderate, high, severe) probability (low, moderate, high) duration (temporary, permanent)
Step 2:	The IRB Administrative Team or convened IRB determines whether the following are factors in the study: health and vulnerability of subjects previously reported adverse events PI and research team prior experience PI history (previous causes for concern?)
Step 3:	The IRB Administrative Team or convened IRB assigns a review frequency that is appropriate to the risk to subjects.
Step 4:	As an alternative (or in addition) to increased review frequency, the IRB may elect to implement any of the following measures: Have an IRB member monitor the consent process. Have an IRB member or third-party observe research activities. Implement stronger controls to protect privacy and confidentiality. Interview subjects following their participation.

Reporting IRB Review and Approval to Clients (Certification)

Assuming IRB approval of the research protocol, the PI and Contracts Representative are responsible for notifying the client that the work is approved for initiation. Department of Health and Human Services (DHHS), other Federal Agencies and Industrial clients receive notification of IRB review as part of the Grant application or by way of an HHS 310 Form, which may be submitted with the proposal or after the activities have been approved by the IRB. The IRB will prepare a 310 Form at the PI's request.

All Department of Energy-related (DOE) projects are reported via the DOE IRB database on a fiscal year basis.