Research

Human Research Protection Program Policy and Procedure Manual - Section 3

3 IRB Review Process
3.1 Purpose
3.2 Definitions
3.3 Human Participants Research Determination
3.4 Exempt Studies

3.4.1 Limitations on Research Participants
3.4.2  Categories of Exempt Research
3.4.3 FDA Exemptions
3.4.4 Additional Protections
3.4.5 Exemption Request Procedures

3.5 Expedited Review
3.5.1 Categories of Research Eligible for Expedited Review
3.5.2 Expedited Review Procedures
3.5.3 Informing the IRB
3.6 Convened IRB Meetings

3.6.1  IRB Meeting Schedule
3.6.2 Preliminary Review
3.6.3 Primary Reviewers
3.6.4 Pre-Meeting Distribution of Documents
3.6.5 Materials Received by the IRB
3.6.6 Quorum
3.6.7 Meeting Procedures
3.6.8 Guests
3.6.9 IRB Member Conflicts of Interest

3.7 Criteria for IRB Approval of Research

3.7.1 Risk/Benefit Assessment
3.7.1.1  Scientific Merit
3.7.2 Selection of Participants is Equitable
3.7.2.1 Recruitment of Participants
3.7.3 Informed Consent
3.7.4 Data Safety Monitoring
3.7.5 Privacy and Confidentiality
3.7.6 Vulnerable Populations

3.8 Additional Considerations during IRB Review and Approval of Research

3.8.1 Determination of Risk
3.8.2 Period of Approval
3.8.2.1 Review More Often Than Annually
3.8.3 Independent Verification That No Material Changes Have Occurred
3.8.4 Consent Monitoring
3.8.5 Investigator Conflicts of Interest
3.8.6 Significant New Findings
3.8.7 Advertisements
3.8.8 Payment to Research Participants
3.8.9 Recruitment Incentives
3.8.10 Certificates of Confidentiality (CoC)
3.8.11 Compliance with all Applicable State and Local Laws

3.9 Possible IRB Actions
3.10 Study Suspension and Termination
3.10.1 Suspension/Termination

3.11 Continuing Review

3.11.1 Approval Period
3.11.2 Continuing Review Process
3.11.3 Expedited Review of Continuing Review
3.11.4 Lapse in Continuing Review

3.12 Amendment to an Approved Protocol

3.12.1 Expedited review of Protocol Amendments
3.12.2 Full Board Review of Protocol Amendments

3.13 Reporting IRB Actions
3.14 Appeal of IRB Decisions

 

3 IRB Review Process

3.1 Purpose

The following describe the procedures required for the review of research by the IRB.

 

3.2 Definitions

Minimal risk.  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.


Minor change.  A minor change is one which, in the judgment of the IRB reviewer, makes no substantial alteration in:

  1. the level of risks to participants
  2. the research design or methodology (adding procedures that are not eligible for expedited review [See Section 3.5] would not be considered a minor change)
  3. the qualifications of the research team
  4. the facilities available to support safe conduct of the research 
  5. any other factor which would warrant review of the proposed changes by the convened IRB. 

 

Quorum. A quorum of the IRB consists of a simple majority of the voting membership, including at least one member whose primary concern is in a non-scientific area.  If research involving an FDA-regulated article is involved, a licensed physician must be included in the quorum.


Suspension of IRB approval. A suspension is a directive of the convened IRB or other authorized individual (See Section 3.10) to temporarily stop short some or all previously approved research activities.  Suspended protocols remain open and require continuing review.


Termination of IRB approval. A directive of the convened IRB to stop permanently all activities in a previously approved research protocol. Terminated protocols are considered closed and no longer require continuing review.

 

3.3 Human Research Determination

The responsibility for initial determination as to whether an activity constitutes human  research rests with the investigator.  The investigator should make this determination based on the definitions of “human participant” and “research” in Section 1.4.  Since the University will hold them responsible if the determination is not correct, investigators may request a confirmation that an activity does not constitute human research from RPO. The request may be made verbally, by phone contact, by email, or through a formal written communication.  All requests must include sufficient documentation of the activity to support the determination. 


Determinations as to whether an activity constitutes human research will be made according to the definitions in Section 1.4.  Determinations regarding activities that either clearly are, or clearly are not, human research, may be made by the IRB Manager.  Determinations regarding less clear-cut activities will be referred to the IRB Chair, who may make the determination or refer the matter to the full IRB.


3.4 Exempt Studies

All research using human participants must be approved by the institution.  Certain categories of research (i.e., “exempt research”) do not require convened IRB review and approval.  Exempt research is subject to institutional review and must be determined by the IRB Chair, Vice Chair, or the Director of RPO or designee.

The exemption is good for three years. If the research extends beyond that date, the researcher has to request another exemption.

 

3.4.1 Limitations on Research Participants

Vulnerable Populations:

  • Children: Exemptions for research do not apply, except for use of exempt category (4)[see 46.101(b)(4)] for secondary data analysis of data about children.
  • Children:  All research involving an interaction or intervention with children requires full board review.  
  • Prisoners: exemptions do NOT apply. IRB review is required.

 

3.4.2 Categories of Exempt Research

With the above exceptions, research activities not regulated by the FDA (see Section 3.4.3 for FDA Exemptions) in which the only involvement of human participants will be in one or more of the following categories are exempt from IRB review, but require institutional review and determination:

  1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as
    • research on regular and special education instructional strategies, or
    • research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
  2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless:
    • information obtained is recorded in such a manner that human participants can be identified, directly or through identifiers linked to the participants; and 
    • any disclosure of the human participants' responses outside the research could reasonably place the participants at risk of criminal or civil liability or be damaging to the participant’s financial standing, employability, or reputation.
  3. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (2), if:
    • the human participants are elected or appointed public officials or candidates for public office; or 
    • Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.
  4. Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that participants cannot be identified, directly or through identifiers linked to the participants. NOTE: In order to be eligible for this exemption, all of the materials have to exist at the time the research is proposed.
  5. Research and demonstration projects which are conducted by or subject to the approval of federal Department or Agency heads, and which are designed to study, evaluate, or otherwise examine:
    • Public benefit or service programs; 
    • Procedures for obtaining benefits or services under those programs; 
    • Possible changes in or alternatives to those programs or procedures; or 
    • Possible changes in methods or levels of payment for benefits or services under those programs.
      Such projects must be conducted pursuant to specific federal statutory authority, there must be no statutory requirements for IRB review, the research must not involve significant physical invasions or intrusions upon the privacy of participants, and the exemption must be invoked only with authorization or concurrence by the funding agency.
  6. Taste and food quality evaluation and consumer acceptance studies,
    • If wholesome foods without additives are consumed; or 
    • If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

 

3.4.3 FDA Exemptions

The following categories of clinical investigations are exempt from the requirements of IRB review:

  1. Emergency use of a test article, provided that such emergency use is reported to the IRB within 5 working days. Any subsequent use of the test article at the institution is subject to IRB review. [21 CFR 56.104(c)]
  2. Taste and food quality evaluations and consumer acceptance studies, if wholesome foods without additives are consumed or if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural, chemical, or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture. [21 CFR 56.104(d)]

 

3.4.4 Additional Protections

Although exempt research is not covered by the federal regulations, this research is not exempt from the ethical guidelines of the Belmont Report. The individual making the determination of exemption will determine whether to require additional protections for participants in keeping with the guidelines of the Belmont Report. 


3.4.5 Exemption Request Procedures

Investigators must submit “IRB Form #1” including, but not limited to, the following documentation:

  1. a summary of the research
  2. a description of the research procedures
  3. consent documents
  4. plan for privacy and confidentiality
  5. plan for dissemination of findings
  6. a copy of the proposal if the research is externally funded
  7. expected date of completion


The application must be signed and dated by the responsible Principal Investigator.

Investigators will be given feedback either by phone or email as to the qualification of the application for exempt status. Once institutional review is completed, IRB staff will send an email and paper notification to the PI of the results of the review.


3.5 Expedited Review

An IRB may use the expedited review procedure to review either or both of the following:

  1. some or all of the research appearing on the list of categories of research eligible for expedited review and found by the reviewer(s) to involve no more than minimal risk,
  2. minor changes in previously approved research during the period (of one year or less) for which approval is authorized


At Brown University expedited categories of review cannot be used for the initial review of research involving children, except for use of expedited category (5) for secondary data analysis of data about children.  Initial review of all research involving an interaction or intervention with children requires full board review.


3.5.1 Categories of Research Eligible for Expedited Review

[63 FR 60364-60367, November 9, 1998]
The activities listed below should not be deemed to be of minimal risk simply because they are included on this list. Inclusion on this list merely means that the activity is eligible for review through the expedited review procedure when the specific circumstances of the proposed research involve no more than minimal risk to human participants.

  • The categories in this list apply regardless of the age of participants, except as noted.
  • The expedited review procedure may not be used where identification of the participants and/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 no greater than minimal.
  • The expedited review procedure may not be used for classified research involving human participants.
  • The standard requirements for informed consent (or its waiver, alteration, or exception) apply regardless of the type of review--expedited or convened--utilized by the IRB.


Research Categories one (1) through seven (7) pertain to both initial and continuing IRB review:

(1) Clinical studies of drugs and medical devices only when condition (a) or (b) is met.

(a) Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the acceptability of the risks associated with the use of the product is not eligible for expedited review.)

(b) Research on medical devices for which (i) an investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.

 

(2) Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:

(a) from healthy, nonpregnant adults who weigh at least 110 pounds. For these participants, the amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more frequently than 2 times per week; or

(b) from other adults and children1, considering the age, weight, and health of the participants, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected. For these participants, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection may not occur more frequently than 2 times per week. [1Children are defined in the DHHS regulations as "persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted."][45 CFR 46.402(a)]

 

(3) Prospective collection of biological specimens for research purposes by noninvasive means. Examples:

(a) hair and nail clippings in a nondisfiguring manner;

(b) deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction;

(c) permanent teeth if routine patient care indicates a need for extraction;

(d) excreta and external secretions (including sweat);

(e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gum base or wax or by applying a dilute citric solution to the tongue;

(f) placenta removed at delivery;

(g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor;

(h) supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic techniques;

(i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings;

(j) sputum collected after saline mist nebulization.

 

(4) Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where medical devices are employed, they must be cleared/approved for marketing. (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.) Examples:

(a) physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the participant or an invasion of the participant’s privacy;

(b) weighing or testing sensory acuity;

(c) magnetic resonance imaging;

(d) electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and echocardiography;

(e) moderate exercise, muscular strength testing, body composition assessment, and flexibility testing where appropriate given the age, weight, and health of the individual.


(5) Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for nonresearch purposes (such as medical treatment or diagnosis). [NOTE: Some research in this category may be exempt from the DHHS regulations for the protection of human subjects. See Exempt Categories and 45 CFR 46 101(b)(4). This listing refers only to research that is not exempt.]

(6) Collection of data from voice, video, digital, or image recordings made for research purposes.

(7) Research on individual or group characteristics or behavior (including, but not limited to, research on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies. [NOTE: Some research in this category may be exempt from the DHHS regulations for the protection of human subjects. See Exempt Categories and 45 CFR 46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.]

(8) Continuing review of research previously approved by the convened IRB as follows:

(a) where (i) the research is permanently closed to the enrollment of new participants; (ii) all participants have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of participants; or

(b) where no participants have been enrolled and no additional risks have been identified; or

(c) where the remaining research activities are limited to data analysis.
[Of note, category (8) identifies three situations in which research that is greater than minimal risk and has been initially reviewed by a convened IRB may undergo subsequent continuing review by the expedited review procedure.

 

For a multi-center protocol, an expedited review procedure may be used by the IRB at a particular site whenever the conditions of category (8)(a), (b), or (c) are satisfied for that site. However, with respect to category 8(b), while the criterion that "no participants have been enrolled" is interpreted to mean that no participants have ever been enrolled at a particular site, the criterion that "no additional risks have been identified" is interpreted to mean that neither the investigator nor the IRB at a particular site has identified any additional risks from any site or other relevant source.]

(9) 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.

[Under Category (9), an expedited review procedure may be used for continuing review of research not conducted under an investigational new drug application or investigational device exemption where categories (2) through (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. The determination that "no additional risks have been identified" does not need to be made by the convened IRB.]


3.5.2 Expedited Review Procedures

Investigators must submit “IRB Form #1” including, but not limited to, the following documentation:

  1. a summary of the research;
  2. a description of the research procedures
  3. consent documents
  4. plan for privacy and confidentiality
  5. plan for dissemination of findings
  6. a copy of the proposal if the research is externally funded
  7. expected date of completion


The application must be signed and dated by the responsible Principal Investigator.

Under an expedited review procedure, the review may be carried out by the IRB Chair or by one or more reviewers designated by the Chair from among members of the IRB.  

The designees must be experienced (having served on the IRB for at least one year) voting members of the IRB.  Selected reviewers will be knowledgeable of the requirements to approve research under expedited review.  IRB members with a conflict of interest in the research (see Section 3.6.9) will not be selected.

When reviewing research under an expedited review procedure, the IRB Chair, or designated IRB member(s), should receive and review all documentation that would normally be submitted for a full-board review including the complete protocol, a progress report form summarizing the research since the previous review (including adverse events), notes from the pre-screening conducted by the RPO staff, the current consent documentation and determine the regulatory criteria for use of such a review procedure.

The reviewer(s) conducting initial or continuing review determine whether the research meets the criteria allowing review using the expedited procedure and if so, whether the research meets the regulatory criteria for approval.  If the research does not meet the criteria for expedited review, the reviewer will indicate that the research requires full review by the IRB; and the protocol will be placed on the agenda for an upcoming IRB meeting.

In reviewing the research, the reviewers will follow the Review Procedures described in Sections 3.8 & 3.9 and may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. A research activity may be disapproved only after review in accordance with the non-expedited procedure set forth below.

Reviewers will indicate approval, required modifications, or disapproval in writing, i.e. via email. If modifications are required, RPO staff will inform the investigator by e-mail. If the modifications are minor, the RPO staff may determine if the investigator has sufficiently addressed the modifications. If the modifications are major, or if the reviewer(s) request it, the modified protocol will be sent back to the IRB member(s) for further review.

In the event that expedited review is carried out by more than one IRB member and the expedited reviewers disagree, the RPO Director and/or IRB Chair may make a final determination. Upon the discretion of the RPO Director or IRB Chair, the protocol will be submitted to the IRB for review.

 

3.5.3 Informing the IRB

IRB members will be apprised of all expedited review approvals by means of a list in the meeting agenda.  Any IRB member can request to review the full protocol by contacting RPO.


3.6 Convened IRB Meetings

Except when an expedited review procedure is used, the IRB will conduct initial and continuing reviews of all research at convened meetings at which a quorum of the members is present.


3.6.1 IRB Meeting Schedule

The IRB meets on a regular basis throughout the year.  The schedule for the IRB may vary due to holidays or lack of quorum.  The schedule for IRB meetings be found on the RPO website.  Special meetings may be called at anytime by the Chair or the Director.


3.6.2 Preliminary Review

Investigators must submit “IRB Form #1” including, but not limited to, the following documentation:

  1. a summary of the research;
  2. a description of the research procedures
  3. consent documents
  4. plan for privacy and confidentiality
  5. plan for dissemination of findings
  6. a copy of the proposal if the research is externally funded.
  7. expected date of completion.


RPO staff will perform a preliminary review of all protocol materials submitted for determination of completeness and accuracy.  Only complete submissions will be placed on the IRB agenda for review.  The investigator will be informed either by e-mail, phone, or in person of missing materials and the necessary date of receipt for inclusion on that month’s agenda. In the case of a PI who is submitting a protocol for the first time or an investigator who may not be well-versed in the protocol submission procedures, individualized IRB consultations can be arranged.  Specific questions about the IRB policies and procedures, assistance with the determination of whether a particular protocol is human research or not and what particular forms are required can be submitted to RPO staff for information and/or clarification.  Individual appointments with RPO staff can also be arranged and are strongly recommended for first-time submissions.


3.6.3 Primary and Secondary Reviewers

After it has been determined that the protocol submission is complete, RPO staff, with the assistance of the IRB Chair, as necessary, will assign protocols for review paying close attention to the scientific content of the protocol and the potential reviewer’s area of expertise.  At least one reviewer will be assigned to each protocol and a reviewer may be assigned several protocols or other research items for review.  Reviewers are assigned to all protocols requiring initial review and to all modifications.  When the IRB is presented with a protocol which may be outside of the knowledge base of any of the IRB members, an outside consultant will be sought.


The primary reviewers are responsible for:

  1. having a thorough knowledge of all of the details of the proposed research.
  2. performing an in-depth review of the proposed research.
  3. leading the discussion of the proposed research at the convened meeting, presenting both positive and negative aspects of the research, and leading the IRB through the regulatory criteria for approval (See Section 3.8). 
  4. making suggestions for changes to the proposed research, where applicable.

 

If the primary reviewer is absent from the meeting, a new reviewer may be assigned, providing the new reviewer has reviewed the materials prior to the meeting.  Additionally, an absent reviewer can submit their written comments for presentation at the convened meeting, as long as there is another reviewer present at the convened meeting, who can serve as the primary reviewer.  It should be noted that IRB members receive, and are expected to review, the entire protocol package for all studies, not just the ones to which they are assigned as reviewers.


3.6.4 Pre-Meeting Distribution of Documents

All required materials need to be submitted (in full) by the last day of the month in order to be included on the IRB agenda of the following month.  Deadline dates can vary occasionally, and the RPO web page should be checked for the latest information.


The meeting agenda will be distributed to the IRB members prior to the meeting.  The agenda packet includes the IRB agenda, prior month’s meeting minutes, applicable business items, appropriate continuing education materials, and protocol review materials.  IRB members receive their review materials one week before the scheduled meeting, whenever possible, to allow sufficient time for the review process.


3.6.5 Materials received by the IRB

Each IRB member receives the following documentation, as applicable:
 
1.    complete protocol application form
2.    project description (complete protocol description)
3.    proposed consent /parental permission /assent form(s)
4.    recruitment materials /participant information
5.    data collection documents (including surveys and questionnaires)
6.    other related documents, as necessary

At least one reviewer must receive and review:  relevant grant applications; the sponsor’s protocol (when one exists); the investigator’s brochure (when one exists); the DHHS-approved sample informed consent document (when one exists); the complete DHHS-approved protocol (when one exists).

Any IRB member may request any of the material provided to the primary and secondary reviewers by contacting RPO.

If an IRB member requires additional information to complete the review, they may contact the investigator directly or RPO to make the request of the investigator.


3.6.6 Quorum

A quorum consists of a simple majority of the voting membership, including at least one member whose primary concern is in a non-scientific area.  If research involving an FDA-regulated article is involved, a licensed physician must be included in the quorum.    The IRB Chair, with the assistance of the IRB staff, will confirm that an appropriate quorum is present before calling the meeting to order. The IRB Chair will be responsible to ensure that the meetings remain appropriately convened. 

A quorum must be maintained for each vote to occur.  RPO staff takes note of arrivals and departures of all members and notifies the chair if a quorum is not present.  If a quorum is not maintained, the protocol must be deferred or the meeting must be terminated.

Members are considered present and counted towards the quorum if participating through teleconferencing or videoconferencing.  In this case the member must have received all pertinent material prior to the meeting and must be able to participate actively and equally in all discussions.

Opinions of absent members that are transmitted by mail, telephone, facsimile or e-mail may be considered by the attending IRB members but may not be counted as votes or to satisfy the quorum for convened meetings.


3.6.7 Meeting Procedures

The IRB Chair, or Vice Chair in the event that the IRB Chair is absent, will call the meeting to order, once it has been determined that a quorum is in place.  The Chair or Vice Chair will remind IRB members to recuse themselves from the discussion and vote by leaving the room where there is a conflict.  The IRB will review and discuss the IRB minutes from the prior meeting and determine if there are any revisions/corrections to be made.  If there are no changes to be made, the minutes will be accepted as presented and considered final.  If it is determined that revisions/corrections are necessary, the minutes will be amended and presented at the following IRB meeting, if requested by the IRB.

The IRB reviews all submissions for initial and continuing review, as well as requests for amendments.  The reviewer(s) presents an overview of the research and leads the IRB through the completion of the regulatory criteria.  All members present at a convened meeting have full voting rights, except in the case of a conflict of interest.  In order for the research to be approved, it must receive the approval of a majority of those voting members present at the meeting.  

It is the responsibility of the RPO staff to record the proceedings of the session and to take minutes at each IRB meeting.


3.6.8 Guests

At the discretion of the IRB, the PI may be invited to the IRB meeting to answer questions about their proposed or ongoing research.  The PI may not be present for the discussion or vote on their research.

Other guests may be permitted to attend IRB meetings at the discretion of the IRB Chair and the RPO Director.  Guests may not speak unless requested by the IRB and may be required to sign a confidentiality agreement.


3.6.9 IRB Member Conflicts of Interest

IRB members and consultants will not participate in any IRB action taken, including the initial and continuing review of any project, in which the member has a conflicting interest, except to provide information requested by the IRB.  IRB members are expected to self-identify conflicting interests.  A full board reviewer or expedited reviewer with a conflict of interest must notify the RPO staff who will re-assign the protocol.  Roles that would present a conflict of interest include, but are not limited to, principal investigator, co-investigator, and graduate student advisor.

Except when requested by the IRB to be present to provide information, IRB members will absent themselves from the meeting room when the IRB reviews research in which they have a conflicting interest.  The Chair will allow for board discussion once the conflicted member has recused him/herself.  The absent member is not counted toward quorum and his/her absence during the discussion and vote on the protocol will be noted in the IRB meeting minutes.

If the conflict of interest status of an IRB member changes during the course of a study, the IRB member is required to declare this to the IRB Chair and/or RPO Director.


3.7b Criteria for IRB Approval of Research

In order for the IRB to approve human research, it must determine that the following requirements are satisfied:

(1) Risks to participants are minimized: (i) by using procedures which are consistent with sound research design and which do not unnecessarily expose participants to risk, and (ii) whenever appropriate, by using procedures already being performed on the participants for diagnostic or treatment purposes.

(2) Risks to participants are reasonable in relation to anticipated benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies participants would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

(3) Selection of participants is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disable persons, or economically or educationally disadvantaged persons.

(4) Informed consent will be sought from each prospective participant or the participant's legally authorized representative, in accordance with, and to the extent required by §46.116.

(5) Informed consent will be appropriately documented, in accordance with, and to the extent required by §46.117.

(6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of participants.

(7) When appropriate, there are adequate provisions to protect the privacy of participants and to maintain the confidentiality of data.

(8) When some or all of the participants are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these participants.


3.7.1 Risk/Benefit Assessment

The goal of the assessment is to ensure that the risks to research participants posed by participation in the research are justified by the anticipated benefits to the participants or society. Toward that end, the IRB must:

  1. judge whether the anticipated benefit, either of new knowledge or of improved health for the research participants, justifies asking any person to undertake the risks;
  2. disapprove research in which the risks are judged unreasonable in relation to the anticipated benefits.


The assessment of the risks and benefits of proposed research - one of the major responsibilities of the IRB - involves a series of steps:

  1. identify the risks associated with the research, as distinguished from other risks, such as the risks of therapies the participants would receive even if not participating in research;
  2. determine whether the risks will be minimized to the extent possible; 
  3. identify the probable benefits to be derived from the research;
  4. determine whether the risks are reasonable in relation to the benefits to participants, if any, and assess the importance of the knowledge to be gained;
  5. ensure that potential participants will be provided with an accurate and fair description of the risks or discomforts and the anticipated benefits;


Risks to participants are minimized:

  1. by using procedures which are consistent with sound research design and which do not unnecessarily expose participants to risk; and
  2. whenever appropriate, by using procedures already being performed on the participants for diagnostic or treatment purposes.


Risks to participants are reasonable in relation to anticipated benefits, if any, and to the importance of the knowledge that may reasonably be expected to result.

  1. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research - as distinguished from risks and benefits of therapies participants would receive even if not participating in the research.
  2. The IRB should not consider possible long-range effects of applying knowledge gained in the research (e.g., the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

 

3.7.1.1 Scientific Merit

In order to assess the risks and benefits of the proposed research, the IRB must determine that:

  • The research uses procedures consistent with sound research design;
  • The research design is sound enough to reasonably expect the research to answer its proposed question; and
  • The knowledge expected to result from this research is sufficiently important to justify the risk.


In making this determination, the IRB may draw on its own knowledge and disciplinary expertise, or the IRB may draw on the knowledge and disciplinary expertise of others, such as reviews by a funding agency or departmental review.


3.7.2 Selection of participants is equitable.

The IRB determines by viewing the application, protocol, and other research project materials that the selection of participants is equitable with respect to gender, age, class, etc. The IRB will not approve a study that does not provide adequately for the equitable selection of participants or has not provided an appropriate scientific and ethical justification for excluding classes of persons who might benefit from the research. In making this determination, the IRB evaluates: the purposes of the research; the setting in which the research occurs; scientific and ethical justification for including vulnerable populations such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons; the scientific and ethical justification for excluding classes of persons who might benefit from the research; and the inclusion/exclusion criteria.


At the time of the continuing review the IRB will determine that the PI has followed the  selection criteria that s/he originally set forth at the time of the initial IRB review and approval.


3.7.2.1 Recruitment of Participants

The investigator will provide the IRB with all recruiting materials to be used in identifying participants including recruitment methods, advertisements, and payment arrangements.  See Section 3.8.7 for a discussion of IRB review of advertisements, Section 3.8.8 for a discussion of IRB review of payments.

 

3.7.3    Informed Consent

The IRB will ensure that informed consent will be sought from each prospective participant or the participant’s legally authorized representative, in accordance with, and to the extent required by 45 CFR 46.116 and 21 CFR 50.20.  In addition, the Committee will ensure that informed consent will be appropriately documented in accordance with, and to the extent required by 45 CFR 46.117 and 21 CFR 50.27.  See Section 5 for detailed policies on informed consent.


3.7.4 Data Safety Monitoring

The IRB determines that, where appropriate, the research plan makes adequate provision for monitoring the data to ensure the safety of participants. For research in which risks are substantial, the IRB may require a general description of the data and safety-monitoring plan to be submitted to the IRB as part of the protocol. This plan should contain procedures for reporting adverse events (AEs). In general, it is desirable for a Data and Safety Monitoring Board (DSMB) to be established by the study sponsor for research that is blinded, involves multiple sites, involves vulnerable participants, or employs high-risk interventions. For some studies the National Institutes of Health (NIH) require a DSMB. The IRB has the authority to require a DSMB as a condition for approval of research where it determines that such monitoring is needed. When DSMBs are utilized, IRBs conducting continuing review of research may rely on a current statement from the DSMB indicating that it has reviewed, and will continue to review, study-wide AEs, interim findings, and any recent literature that may be relevant to the research, in lieu of requiring that this information be submitted directly to the IRB.


3.7.5 Privacy and Confidentiality

The IRB will determine whether adequate procedures are in place to protect the privacy of participants and to maintain the confidentiality of the data. 

Definitions

  • Privacy - having control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with others.
  • Confidentiality - methods used to ensure that information obtained by researchers about their participants is not improperly divulged.


Regulations
46.102(f) Human subject means a living individual about whom an investigator… conducting research obtains

  1. data through intervention or interaction with the individual,
    or
  2. identifiable private information.
  • Private information - information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).
  • Identifiable information – information where the identity of the participant is or may readily be ascertained by the investigator or associated with the information.


Privacy
The IRB must determine whether the activities in the research constitute an invasion of privacy.  In order to make that determination, the IRB must obtain information regarding how the investigators are getting access to participants or participants’ information and the participants expectations of privacy in the situation.  Investigators must have appropriate authorization to access the participants or the participants’ information.

Confidentiality
Confidentiality and anonymity are not the same. If anyone, including the investigator, can readily ascertain the identity of the participants from the data, then the research is not anonymous and the IRB must determine if appropriate protections are in place to minimize the likelihood that the information will be inappropriately divulged.  The level of confidentiality protections should be commensurate with the potential of harm from inappropriate disclosure.

At the time of initial review, the IRB ensures that the privacy and confidentiality of research participants is protected. The IRB assesses whether there are adequate provisions to protect participant privacy and maintain confidentiality. The IRB does this through the evaluation of the:

  • methods used to obtain information about participants,
  • methods used to obtain information about individuals who may be recruited to participate in studies
  • the use of personally identifiable records and 
  • the methods to protect the confidentiality of research data.

 

In some cases, the IRB may also require that a Certificate of Confidentiality be obtained to additionally protect research data (See Section 4.16.8). The PI will provide the information regarding the privacy and confidentiality of research participants at the time of initial review through the completion of the research protocol. The IRB will review all information received from the PI and determine whether or not the privacy and confidentiality of research participants is sufficiently protected.


In reviewing confidentiality protections, the IRB shall consider the nature, probability, and magnitude of harms that would be likely to result from a disclosure of collected information outside the research. It shall evaluate the effectiveness of proposed de-identification techniques, coding systems, encryption methods, storage facilities, access limitations, and other relevant factors in determining the adequacy of confidentiality protections.


3.7.6 Vulnerable Populations

At the time of initial review the IRB will consider the scientific and ethical reasons for including vulnerable participants in research. The IRB may determine and require that, when appropriate, additional safeguards are put into place for vulnerable participants, such as those without decision-making capacity.


The IRB carefully evaluates each protocol to determine if vulnerable participants are included in the study population and what measures have been taken to protect them.


The IRB is required to consider the scientific and ethical reasons for including vulnerable populations in research. The IRB must pay special attention to specific elements of the research plan when reviewing research involving vulnerable participants. These specific elements may include strategic issues such as inclusion and exclusion criteria for selecting and recruiting participants, informed consent and willingness to volunteer, coercion and undue influence and confidentiality of data.


The IRB carefully considers group characteristics, such as economic, social, physical, and environmental conditions, to ensure that the research incorporates additional safeguards for vulnerable participants.  For example, it is not appropriate to focus on prisoners as research participants merely because they are a readily available "captive" population.


The IRB may require additional safeguards to protect potentially vulnerable populations. For instance, the IRB may require that the investigator submit each signed informed consent form to the IRB. The IRB may also require that someone from the IRB oversee the consent process or that a waiting period be established between initial contact and enrollment to allow time for family discussion and questions.


3.8 Additional Considerations during IRB Review and Approval of Research

3.8.1 Determination of Risk

At the time of initial and continuing review, the IRB will make a determination regarding the risks associated with the research protocols.  Risks associated with the research will be classified as either “minimal” or “greater than minimal” based on the “absolute” interpretation of minimal risk. The meeting minutes will reflect the Committee’s determination regarding risk levels for full board protocols.


3.8.2 Period of Approval

At the time of initial review and at continuing review, the IRB will make a determination regarding the frequency of review of the research protocols.  All protocols will be reviewed by the IRB at intervals appropriate to the degree of risk but no less than once per year.  In some circumstances, a shorter review interval (e.g. biannually, quarterly, or after accrual of a specific number of participants) may be required.  The meeting minutes will reflect the IRB’s determination regarding review frequency.


3.8.2.1 Review More Often than Annually

Research that meets any of the following criteria may require review more often than annually:

  1. significant risk to research participants (e.g., death, permanent or long lasting disability or morbidity, severe toxicity) without the possibility of direct benefit to the participants;
  2. the involvement of especially vulnerable populations likely to be subject to coercion (e.g., terminally ill)
  3. a history of serious or continuing non-compliance on the part of the PI.


The following factors will also be considered when determining which studies require review more frequently than on an annual basis:

  1. probability and magnitude of anticipated risks to participants.
  2. likely medical condition of the proposed participants.
  3. overall qualifications of the PI and other members of the research team.
  4. specific experience of the PI and other members of the research team in conducting similar research.
  5. nature and frequency of adverse events observed in similar research at this and other institutions.
  6. novelty of the research making unanticipated adverse events more likely.
  7. any other factors that the IRB deems relevant.

 

In specifying an approval period of less than one year, the IRB may define the period with either a time interval or a maximum number of participants either studied or enrolled.  If a maximum number of participants studied or enrolled is used to define the approval period, it is understood that the approval period in no case can exceed 1 year and that the number of participants studied or enrolled determines the approval period only when that number of participants is studied or enrolled in less than 1 year.

 

3.8.3 Independent Verification that No Material Changes Have Occurred

The IRB recognizes that protecting the rights and welfare of participants sometimes requires that the IRB verify independently, utilizing sources other than the investigator that no material changes occurred during the IRB-designated approval period. Independent verification from sources other than the investigator may be necessary at times, for example, in cooperative studies, or other multi-center research.


The IRB will determine the need for verification from outside sources on a case-by-case basis and according to the following criteria:

  1. protocols where concern about possible material changes occurring without IRB approval have been raised based on information provided in continuing review reports or from other sources.
  2. protocols conducted by PIs who have previously failed to comply with federal regulations and/or the requirements or determinations of the IRB.
  3. protocols randomly selected for internal audit.
  4. whenever else the IRB deems verification from outside sources is relevant.

 

The following factors will also be considered when determining which studies require independent verification:

  1. probability and magnitude of anticipated risks to participants.
  2. likely medical condition of the proposed participants.
  3. probable nature and frequency of changes that may ordinarily be expected in the type of research proposed.

 

In making determinations about independent verification, the IRB may prospectively require that such verification take place at predetermined intervals during the approval period, or may retrospectively require such verification at the time of continuing review, review of amendments, and/or review of adverse events.


If any material changes have occurred without IRB review and approval, the IRB will decide the corrective action to be taken.


3.8.4 Consent Monitoring

In reviewing the adequacy of informed consent procedures for proposed research, the IRB may on occasion determine that special monitoring of the consent process by an impartial observer (consent monitor) is required in order to reduce the possibility of coercion and undue influence.
Such monitoring may be particularly warranted where the research presents significant risks to participants, or if participants are likely to have difficulty understanding the information to be provided. Monitoring may also be appropriate as a corrective action where the IRB has identified problems associated with a particular investigator or a research project.
See Section 5.7 for a detailed discussion of consent monitoring.

 

3.8.5 Investigator Conflicts of Interest

The protocol form asks protocol-specific questions regarding conflict of interest for the investigators and key personnel.  If a conflict of interest exists, final IRB approval of a protocol cannot be given until an approved conflict management plan that adequately protects the human participants in the protocol is in place.


3.8.6 Significant New Findings

During the course of research, significant new knowledge or findings about the topic under study may develop.  The PI must report any significant new findings to the IRB, and the IRB will review them with regard to the impact on the participants’ rights and welfare.  Since the new knowledge or findings may affect the risks or benefits to participants or participants' willingness to continue in the research, the IRB may require, during the ongoing review process, that the PI contact the currently enrolled participants to inform them of the new information. The IRB will communicate this to the PI. The informed consent should be updated and the IRB may require that the currently enrolled participants be re-consented, acknowledging receipt of this new information and for affirming their continued participation.


3.8.7 Advertisements

The IRB must approve all advertisements prior to posting and/or distribution for studies that are conducted under the purview of the Brown University IRB. The IRB will review:

  1. information contained in the advertisement
  2. mode of communication
  3. final copy of printed advertisements, when necessary
  4. final audio/video taped advertisements, when necessary

 

This information should be submitted to the IRB with the initial application or as an amendment to the protocol.


The IRB reviews the material to assure that the material is accurate and is not coercive or unduly optimistic, creating undue influence to participate which includes but is not limited to:

  1. statements implying a certainty of favorable outcome or other benefits beyond what was outlined in the consent document and the protocol
  2. using terms like “new treatment,” “new medication,” or “new drug” without explaining that the test article was investigational
  3. promising “free medical treatment” when the intent was only to say participants will not be charged for taking part in the investigation
  4. emphasis on payment or the amount to be paid, such as bold type or larger font on printed media
  5. inclusion of exculpatory language
  6. claims, either explicitly or implicitly, that the drug, biologic or device was safe or effective for the purposes under investigation and/or that the test article was known to be equivalent or superior to any other drug, biologic or device

 

Any advertisement to recruit participants should be limited to the information the prospective participants need to determine their eligibility and interest. When appropriately worded, the following items may be included:

  1. name and address of the investigator and/or research facility.
  2. condition being studied and/or the purpose of the research.
  3. criteria that will be used to determine eligibility for the study, in summary form.
  4. time or other commitment required of the participants.
  5. location of the research and the person or office to contact for further information.
  6. clear statement that this is research and not treatment.
  7. brief list of potential benefits (e.g. no cost of health exam).


3.8.8 Payment to Research Participants

Payment to research participants may be an incentive for participation or a way to reimburse a participant for travel and other experiences incurred due to participation. However, payment for participation is not considered a research benefit.  Regardless of the form of remuneration, investigators must take care to avoid coercion of participants.  Payments should reflect the degree of risk, inconvenience, or discomfort associated with participation. The amount of compensation must be proportional to the risks and inconveniences posed by participation in the study.

Investigators who wish to pay research participants must indicate in their research protocol the justification for such payment. Such justification should:

  • substantiate that proposed payments are reasonable and commensurate with the expected contributions of the participant;
  • state the terms of the participation agreement and the amount of payment in the informed consent form; and
  • substantiate that payments are fair and appropriate and that they do not constitute (or appear to constitute) undue pressure on the participate to volunteer for the research study.

 

The IRB must review both the amount of payment and the proposed method of disbursement to assure that neither entails problems of coercion or undue influence.

Credit for payment should accrue and not be contingent upon the participant completing the entire study.  Whenever possible, the IRB does not allow the entire payment to be contingent upon completion of the entire study.  Any amount paid as bonus for completion of the entire study should not be so great that it becomes coercive. 

The consent form should describe the terms of payment and the conditions under which participants would receive partial payment or no payment (e.g., if they withdraw from the study before their participation is completed).


3.8.9 Recruitment Incentives

Payment arrangements among sponsors, organizations, investigators, and those referring research participants may place participants at risk of coercion or undue influence or cause inequitable selection.  Payment in exchange for referrals of prospective participants from others (“finder’s fees”) is not permitted. Similarly payments designed to accelerate recruitment that is tied to the rate or timing of enrollment (“bonus payments”) are also not permitted.


3.8.10 Certificates of Confidentiality (CoC)

Where research involves the collection of highly sensitive information about individually identifiable participants, the IRB may determine that special protections are needed to protect participants from the risks of investigative or judicial processes. In such situations the IRB may require that an investigator obtain a Department of Health and Human Services (DHHS) Certificate of Confidentiality (CoC).


For studies not funded by DHHS, if there is an Investigational New Drug Application (IND) or an Investigational Drug Exemption (IDE), the sponsor can request a CoC from the FDA. The CoC was developed to protect against the involuntary release of sensitive information about individual participants for use in federal, state, or local civil, criminal, administrative, legislative, or other legal proceedings.


The IRB may determine that an investigator should request a certificate of confidentiality from the National Institute of Health (NIH) in cases when the information gathered for the research could be held against the research participant in a court of law. An investigator applies for a certificate of confidentiality through the NIH. The NIH will review the application and make a determination as to whether or not a CoC may be granted for the specific research project.


The CoC does not prohibit voluntary disclosure of information by an investigator, such as voluntary reporting to local authorities of child abuse or of a communicable disease. In addition, the CoC does not protect against the release of information to DHHS or FDA for audit purposes. Consequently, the IRB may require that these conditions for release be stated clearly and explicitly in the informed consent document.


Additional information, regarding CoCs, including the application information necessary for applying for a Certificate of Confidentiality may be obtained on the NIH website.


3.8.11 Compliance with all Applicable State and Local Laws

The IRB follows and must adhere to all applicable state and local laws in the jurisdictions where the research is taking place.  The HRPP and the IRB rely on the University Counsel for the interpretation and application of State law and the laws of any other jurisdiction where research is conducted as they apply to human participants research.


All consent forms must be consistent with applicable state and local laws.

 

3.9 Possible IRB Actions

Approval - the study is approved as submitted.

Specific minor revisions - the protocol and/or consent form require minor revisions, such as wording changes, with replacement language provided or potentially ambiguous language that needs clarification. For full review, the needed revisions are agreed upon at the meeting when the protocol is reviewed.  For expedited review, they are designated by the reviewer(s). These revisions are presented to the PI for incorporation by simple concurrence.

In order to receive approval for a protocol deferred for non-substantive issues:

  1. For full review, the investigator’s response, the revised protocol and the previously submitted protocol is reviewed by the IRB Chair, Vice Chair, or designee. The reviewer(s) may accept the revisions upon receipt and determination of adequacy without further action by the IRB.
  2. For expedited, the investigator’s response, the revised protocol and the previously submitted protocol is given to the same reviewer(s) for re-review.
  3. Approval of the protocol application will not be granted until all deficiencies, if any, are corrected to the satisfaction of the IRB or the reviewer(s). 
  4. The outcome of the IRB's deliberations is communicated to the investigator in writing.


Note: For full review, the expiration date for the protocol is calculated based on the date that the convened IRB reviewed the protocol and NOT on the final approval date.

Deferred for substantive issues - regarding the protocol and/or consent form must be addressed. This action is taken if substantial modification or clarification is required, or insufficient information is provided to judge the protocol application adequately (e.g., the risks and benefits cannot be assessed with the information provided).  IRB approval of the proposed research must not occur until subsequent review by the convened IRB or the expedited reviewer(s) of the material the PI submitted.

In order to receive approval for a protocol deferred for substantive issues:

  1. For full review, the investigator’s response must be submitted for review at a subsequent, convened meeting of the same IRB. RPO provides the IRB with the investigator’s response and the revised protocol. The item is placed on the agenda for re-review at the next meeting.
  2. For expedited review, the investigator’s response, the revised protocol, and the previously submitted protocol are given to the same reviewer(s) for re-review.
  3. Approval of the protocol application will not be granted until all deficiencies, if any, are corrected to the satisfaction of the IRB or the reviewer(s). 
  4. The outcome of the IRB's deliberations is once again communicated to the investigator in writing.
  5. The IRB's determination concerning the subsequent amended submission will be documented in the minutes of the IRB meeting or in the file for expedited review.


Disapproved - The IRB has determined that the research cannot be conducted by employees or agents of the University or otherwise under the auspices of the University.


3.10 Study Suspension and Termination

3.10.1 Suspension/Termination

The IRB may vote to suspend or terminate approval of research not being conducted in accordance with IRB or regulatory requirements or that has been associated with unanticipated problems or serious harm to participants or others.  (See Section 8 for a discussion of unexpected problems.) 
Suspension of IRB approval is a directive of the convened IRB or IRB Chair or RPO Director either to temporarily or permanently stop some or all previously approved research activities short of permanently stopping all previously approved research activities. Suspended protocols remain open and require continuing review. Termination of IRB approval is a directive of the convened IRB to stop permanently all activities in a previously approved research protocol. Terminated protocols are considered closed and no longer require continuing review.

The IRB shall notify the PI in writing of such suspensions or terminations and shall include a statement of the reasons for the IRB's actions. The terms and conditions of the suspension must be explicit. The investigator shall be provided with an opportunity to respond in person or in writing.


The IRB Chair or RPO Director may suspend research to ensure protection of the rights and welfare of participants.  Suspension directives made by the IRB Chair or RPO Director must be reported to a meeting of the convened IRB.

Research may be terminated only by the convened IRB.  Terminations of protocols approved under expedited review must be made by the convened IRB.

When study approval is suspended or terminated by the convened IRB or an authorized individual, in addition to stopping all research activities, the convened IRB or individual ordering the suspension or termination will consider notification of any participants currently participating that the study has been suspended or terminated. The convened IRB or individual ordering the suspension or termination will consider whether procedures for withdrawal of enrolled participants are necessary to protect the rights and welfare of participants, such as: transferring participants to another investigator; making arrangements for care or follow-up outside the research; allowing continuation of some research activities under the supervision of an independent monitor; or requiring or permitting follow-up of participants for safety reasons.

If follow-up of participants for safety reasons is permitted/required by the convened IRB or individual ordering the suspension or termination, the convened IRB or individual ordering the suspension or termination will require that the participants should be so informed and that any adverse events/outcomes be reported to the IRB and the sponsor.


3.11 Continuing Review

The IRB will conduct a continuing review of ongoing research at intervals that are appropriate to the level of risk for each research protocol, but not less than once per year.  Continuing review must occur as long as the research remains active for long-term follow-up of participants, even when the research is permanently closed to the enrollment of new participants and all participants have completed all research-related interventions.  Continuing review of research must occur even when the remaining research activities are limited to the analysis of private identifiable information.


3.11.1 Approval Period

At Brown University, determination of the approval period and the need for additional supervision and/or participation is made by the IRB on a protocol-by-protocol basis. For example, for an investigator who is performing particularly risky research, or for an investigator who has recently had a protocol suspended by the IRB due to regulatory concerns, an on-site review by a subcommittee of the IRB might occur or approval might be subject to an audit of study performance after a few months of enrollment, or after enrollment of the first several participants.

For each initial or continuing approval the IRB will indicate an approval period with an approval expiration date specified.  IRB approval is considered to have lapsed at midnight on the expiration date of the approval.  For a study approved by the convened IRB, the approval period starts on the date that the IRB conducts its final review of the study; that is, the date that the convened IRB approved the research or the date the convened IRB deferred the research for non-substantive issues.  For a study approved under expedited review, the approval period begins on the date the IRB Chair or IRB member(s) designated by the Chair gives final approval to the protocol.

The approval date and approval expiration date are clearly noted on all IRB certifications sent to the PI and must be strictly adhered to. Investigators should allow sufficient time for development and review of renewal submissions.

Review of a change in a protocol ordinarily does not alter the date by which continuing review of the entire protocol must occur.

The regulations make no provision for any grace period extending the conduct of research beyond the expiration date of IRB approval. Therefore, continuing review and re-approval of research must occur by the date when IRB approval expires.  If the IRB performs continuing review within 30 days before the IRB approval period expires, the IRB may retain the anniversary date as the date by which the continuing review must occur.


3.11.2 Continuing Review Process

To assist investigators RPO staff will send out renewal notices to investigators two months in advance of the expiration date; however, it is the investigator’s responsibility to ensure that the continuing review of ongoing research is approved prior to the expiration date. By federal regulation, no extension to that date can be granted.

Investigators must submit the following for continuing review:

  • protocol renewal form;
  • current consent document(s); and
  • other documents, as necessary.


In conducting continuing review of research not eligible for expedited review, IRB members are provided, and review, all of the above material.  The reviewer for that month will review the complete protocol, including any amendments previously approved by the IRB.  At the meeting, the monthly reviewer leads the IRB through the completion of the regulatory criteria for approval.

RPO staff attends the convened meetings and brings the complete protocol files for each protocol on the agenda. The IRB staff will retrieve any additional related materials the IRB members request.

In the case of expedited review, the IRB members may request the IRB office staff to provide them with any additional materials required for the review.

Review of currently approved consent documents must occur during the scheduled continuing review of research by the IRB, but informed consent documents should be reviewed whenever new information becomes available that would require modification of information in the informed consent document.


3.11.3 Expedited Review of Continuing Review

In conducting continuing review under expedited review, the reviewers receive all of the above material.  The reviewer(s) determine whether the research meets the criteria allowing continuing review using the expedited procedure, and if so, whether the research continues to meet the regulatory criteria for approval.   

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 described by expedited review categories (8) and (9) at 63 FR 60364-60367 (see Expedited Review Categories). It is also possible that research activities that previously qualified for expedited review in accordance with 45 CFR 46.110, have changed or will change, such that expedited IRB review would no longer be permitted for continuing review.


3.11.4 Lapse in Continuing Review

The regulations permit no grace period or approval extension after approval expiration.  Research that continues after the approval period has expired is research conducted without IRB approval.  If the continuing review does not occur within the timeframe set by the IRB, all research activities must stop, including recruitment (media advertisements must be pulled), enrollment, consent, interventions, interactions, and data collection, unless the IRB finds that it is in the best interests of individual participants to continue participating in the research interventions or interactions.   This will occur even if the investigator has provided the continuing information before the expiration date. Therefore, investigators must allow sufficient time for IRB review before the expiration date.


RPO is responsible for immediately notifying the investigator of the expiration of approval and that all research activities must stop.

 

If research participants are currently enrolled in the research project and their participation is ongoing, once notified of the expiration of approval the PI must immediately submit to the IRB Chair a list of research participants for whom suspension of the research would cause harm.  Enrollment of new participants cannot occur and continuation of research interventions or interactions for already enrolled participants should only continue when the IRB or IRB Chair finds that it is in the best interest of the individual participants to do so.


Failure to submit continuing review information on time is non-compliance and will be handled according to the non-compliance policy. 

If the study is FDA-regulated, the IRB Chair must follow FDA requirements in 21 CFR 56.108(b)(3) in making their decision.


The sponsoring agency, private sponsor, or other Federal agencies must be informed, as appropriate.


Once approval has expired, IRB review and re-approval must occur prior to re-initiation of the research. If the study approval has lapsed more than 30 days and the PI has not provided the required continuing review information, the PI must submit a new application to the IRB for review and approval. If the study approval has lapsed 30 days or less and the PI provides the required continuing review information, the existing protocol may be reviewed for consideration of continued IRB approval.


If a research protocol receives contingent approval at the time of the continuing review and the approval expires before the PI responds to the contingencies, the PI may not enroll any new participants after the approval expiration date.  Once the PI responds, the existing protocol will be reviewed for continuation.  If the PI does not respond for an extended period, the IRB may vote to administratively close the study.  Decisions of this kind must be made in a manner that ensures that closure will not harm any participants previously enrolled who may require ongoing treatment as part of the research study.


3.12 Amendment to an Approved Protocol

Investigators may wish to modify or amend their approved protocols.  Investigators must seek IRB approval before making any changes in approved research - unless the change is necessary to eliminate an immediate hazard to the participant (in which case the IRB must then be notified at once.)

In order to obtain approval, investigators must submit to the IRB documentation about the proposed changes to the status of the study, including, but not necessarily limited to:

  • description of the changes
  • reasons for the changes
  • brief summary of the overall project
  • revised approved consent/parental permission/assent documents (if applicable) or other documentation that would be provided to participants when such information might relate to their willingness to continue to participate in the study
  • revised or additional recruitment materials
  • any other relevant documents provided by the investigator
  • revised Investigator’s protocol application or sponsor’s protocol (if applicable)


If the changes were requested by another IRB, study-related reasons for the changes must be provided, not simply a statement that another IRB requested them.

RPO staff will determine whether the proposed changes may be approved through an expedited review process, if the changes are minor, or whether the amendment warrants full board review. The reviewer(s) using the expedited procedure has the ultimate responsibility to determine that the proposed changes may be approved through the expedited review procedure and, if not, must refer the amendment for full board review.

The requested changes must not be implemented until IRB approval has been granted, which is usually documented through a memo from RPO.


3.12.1 Expedited review of Protocol Amendments

An IRB may use expedited review procedures to review minor changes in ongoing previously-approved research during the period for which approval is authorized. An expedited review may be carried out by the IRB Chair and/or designee(s) among the IRB members.

The reviewer(s) determine whether the amendments meet the criteria allowing review using the expedited procedure, and if so, whether the research with the proposed amendment meets the regulatory criteria for approval.


3.12.2 Full Board Review of Protocol Amendments

When a proposed change in a research study is not minor (e.g., procedures involving increased risk or discomfort are to be added), then the IRB must review and approve the proposed change at a convened meeting before the change can be implemented. The only exception is a change necessary to eliminate apparent immediate hazards to the research participants. In such a case, the IRB should be promptly informed of the change following its implementation and should review the change to determine that it is consistent with ensuring the participants' continued welfare.

All IRB members are provided with, and review, all documents provided by the investigator.

At the meeting, the primary reviewer presents an overview of the amendments and leads the IRB through the completion of the regulatory criteria for approval.

When the IRB reviews amendments to previously approved research, the IRB considers whether information about those amendments might relate to participants’ willingness to continue to take part in the research and if so, whether to provide that information to participants.


3.13 Reporting IRB Actions

All IRB actions are communicated to the PI, or designated primary contact person for the protocol, in writing by the RPO staff.  For an approval, written notification of approval will be sent.  For a deferral, the notification will include the modifications required for approval along with the basis for requiring those modifications. For a disapproval, termination or suspension, the notification will include the basis for making that decision.

All letters to investigators will be filed in the protocol files maintained by RPO.

The IRB reports its findings and actions to the Institution in the form of its minutes which are stored permanently and securely in the RPO Office.  Copies of minutes are distributed by RPO staff to the Brown University Institutional Official (IO).


3.14 Appeal of IRB Decisions

When an IRB protocol presented at a convened meeting is disapproved, deferred or requires minor modifications, the IRB will notify the PI in writing about the specific deficiencies and the modifications that are necessary for appropriate IRB approval.  The IRB shall include in its written notification a statement of the reasons for its decision and give the investigator an opportunity to respond in person or in writing.


In cases where there is disagreement between the IRB and the PI regarding the nature and extent of the requested changes and these disagreements cannot be resolved amicably in an informal manner, the PI and/or the IRB may make an appeal to the IO for a resolution of the matter.  The IO may organize a meeting to help facilitate discussion between the IRB and the PI.  While the IO may provide input and make recommendations to the IRB for expeditious resolution of the matter, final recommendations for approval remain under the purview of the IRB.

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