IRB Continuing Review Policy

Boston University
Charles River Campus IRB
Policies and Procedures

Title: Continuing Review
Date: November 23, 2015

Purpose

The purpose of this policy is to outline the procedure for conducting continuing reviews of human subjects research

Policy

All non-exempt human subjects research must be reviewed on a continuing basis. The IRB is responsible for conducting continuing review at intervals appropriate to the degree of risk, but not less than once per year. Continuing review will continue until the study is completed and has been closed out with the IRB.

Research that was initially approved by expedited procedures will be reviewed by expedited procedures at the time of continuing review unless there has been a change to the research that makes it so that the research no longer qualifies for expedited review.

Research that was initially approved by the Full Board will usually require continuing review to be done at the Full Board. There are limited circumstances where research initially approved by the Full Board can undergo expedited review at the time of continuing review. The circumstances are:

• The research project involves only activities described by expedited review categories (8)* or (9)**; or
• Research project previously approved by the IRB at a convened meeting progresses to the stage where all of the remaining human subjects research activities involve no more than minimal risk to the subjects and fall within the scope of one or more of expedited review categories (2) through (7).

*Category 8

Under category (8), an expedited review procedure may be used for the continuing review of research previously approved by the IRB at a convened meeting as follows:

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

**Category 9

Under category (9), an expedited review procedure may be used for the continuing review of research previously approved by the IRB at a convened meeting that meets the following conditions:

• The research is not conducted under an investigational new drug application (IND) or an investigational device exemption (IDE);
• Expedited review categories (2) through (8) do not apply to the research;
• The IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk to the subjects; AND
• No additional risks of the research have been identified.

With regard to the third condition above, the IRB at a convened meeting must have determined that either (a) the research project as a whole involved no more than minimal risk, or (b) the remaining research activities involving human subjects present no more than minimal risk to the subjects. This determination, particularly with respect to (a), could occur as early as the convened IRB meeting at which the IRB conducted its initial review.

Procedures

Submission of Continuing Review Application

1. The Investigator submits the Continuing Review Application and all applicable documents to the CRC IRB for review including:
   • Consent/assent/information sheet
   • Recruitment/screening materials
   • Questionnaires, surveys, etc.
   • Progress reports
   • DSMB/Monitoring Reports
2. The IRB Coordinator conducts an administrative pre-review to check for missing or incomplete documents and for training requirements. Incomplete submissions are returned to the Principal Investigator (PI).
3. The IRB Coordinator enters the continuing review submission into the IRB tracking system.
4. The IRB Coordinator assigns the Application to the appropriate IRB member and/or IRB Analyst for review.
5. If the continuing review will be reviewed by expedited procedures the IRB Analyst (in their capacity as an IRB member) will serve as the IRB Reviewer. If the continuing review will be reviewed by the Full Board, one of the regular IRB members will be assigned as the Primary Reviewer.

Review Process

1. The IRB Reviewer and/or IRB Analyst will complete the appropriate Reviewer Worksheets and Approval Checklists.
2. The IRB Reviewer will have access to the following documents for the review, as applicable:
   • Continuing Review Application
   • Current consent form/statement
   • Recruitment/screening materials
   • Sponsor/NIH Progress reports
   • DSMB/Monitoring Reports
   • Questionnaires, surveys, etc.
3. The Continuing Review Application includes the following information:
   • The number of participants accrued
   • A summary since the last IRB review of:
     • Adverse events and adverse outcomes experienced by subjects
     • Unanticipated problems involving risks to subjects or others
     • Subject withdrawals
     • The reasons for withdrawals
     • Complaints about the research
     • Amendments or modifications
     • Any relevant recent literature o Any interim findings
     • Any relevant multi-center trial reports
     • The investigator’s current risk-potential benefit assessment based on study results
4. If the study is still open to enrollment, the IRB Reviewer will confirm that:
   • The current consent document is still accurate and complete
   • Any significant new findings are communicated to subjects who have already enrolled
5. The IRB must determine that the regulatory criteria for approval (45 CFR 46.111 and 21 CFR 56.111) are met. The criteria are defined below:
   • Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
   • 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. In evaluating risks and benefits, the Reviewer will consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research).
   • Selection of subjects is equitable. In making this assessment, the Reviewer will take into account the purposes of the research and the setting in which the research will be conducted.
   • Informed consent will be sought from each prospective subject or the subject’s legally authorized representative.
   • Informed consent will be appropriately documented.
   • When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
   • When appropriate, there are adequate provisions 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, 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 subjects.

Lapse of IRB Approval

The IRB Coordinator sends out continuing review e-mail reminders to Principal Investigators approximately eight weeks and two weeks prior to expiration. Once the study expires, the IRB sends an e-mail to the Principal Investigator stating that the study is expired and that all research activities must stop. The expiration date is the last date that the protocol is approved.

Continued participation of already enrolled subjects may occur if:

• There is an over-riding safety concern or ethical issue such that the best interests of individual subjects are served by allowing these subjects to continue to participate in the research.
• There is the prospect of direct benefit.
• Withholding research interventions poses an increase risk to subjects.

If the Principal Investigator believes that it is in the best interest of already enrolled subjects to continue participation, he/she should submit a request to the IRB Director. The request should include the rationale for allowing continued participation of these subjects. The request will be reviewed by the IRB Director and/or IRB Chair. Consultants will be obtained as necessary. Enrollment of new subjects during the lapsed period will not be allowed.

If the Principal Investigator does not submit the Continuing Review Report 30 days after the protocol expiration date, the IRB will terminate the protocol. At this time, the IRB will notify the PI that the protocol has been terminated and that if the PI wishes to continue with the research, he/she must submit a new application to the IRB.

Review Period

Continuing review of research will be conducted at intervals appropriate to the degree of risk but not less than once per year (annually). The IRB may determine that continuing review must occur more frequently than annually. Continuing review may be required more frequently when:

• The research is high-risk
• The research involves novel treatment(s)/intervention(s)
• The PI has deviated/violated from IRB policies and/or federal regulations in the past
• The IRB Application required significant revisions
• The PI is new to research

Calculation of Approval Date

Initial Approval: The date of initial approval is the date that all the required modifications/conditions are determined to be met. The date of expiration will be one year (minus one day) from the approval date unless the IRB determines that more frequent continuing review is necessary.

Continuing Review: For all subsequent continuing reviews, the CRC IRB follows a process for maintaining fixed anniversary dates for the expiration of IRB approvals when: 1) the IRB grants approval for one year at the time of each continuing review, and 2) the IRB performs continuing review and re-approves the research (all conditions/modifications must be met) within 30 days before the IRB approval period expires. If the research study is not submitted AND approved prior to the expiration date, the anniversary date will not be maintained. The new approval date will be the date that all the required modifications/conditions are determined to be met and the date of expiration will be date will be one year (minus one day) from the approval date unless the IRB determines that more frequent continuing review is necessary.

Title: Continuing Review

Author: Cynthia Monahan

Effective Date: October 30, 2014

Last Review/Update Date: November 23, 2015

Revision #: 3

Approved: Cynthia Monahan, IRB Director Kathryn Mellouk, Associate Vice President-Research Compliance

NOTE: This policy applies to research with an initial approval date of January 21, 2019 or later.

Purpose

The purpose of this policy is to outline the procedure for conducting continuing reviews of human subjects research

Policy

Research that requires Continuing Review:
The IRB will conduct continuing review of research requiring review of the convened IRB. The IRB is responsible for conducting continuing review at intervals appropriate to the degree of risk, but not less than once per year.

Research that does not Require Continuing Review:
Unless the IRB determines otherwise, continuing review of research is not required in the following circumstances:

• Exempt research
• Research eligible for expedited review
• Research reviewed by the IRB in accordance with the limited IRB review
• Research that has progressed to the point that it involves only one or more of the following, which are part of the IRB-approved study:
  • Data analysis, including analysis of identifiable private information or identifiable biospecimens
  • Accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care

The IRB may determine that the continuing review is required for any research that falls within any of the above criteria. Instances in which the IRB may determine that continuing review is still required include:

• The research involves topics, procedures, or data that may be considered sensitive or controversial
• The research involves vulnerable populations
• The investigator has minimal experience in research or in the research topic
• The investigator has a history of non-compliance

If the IRB determines that continuing review is required for this research, it will document the rationale in the IRB record and communicate the requirement to the investigator in the IRB determination letter.

If a study is regulated by the FDA, continuing review will be conducted in compliance with the applicable FDA regulations.

Annual Updates for Expedited Research that Does Not Require Continuing Review
The investigator will be required to provide an annual update to the IRB for expedited research that does not require continuing review.

Procedures

SUBMISSION OF CONTINUING REVIEW APPLICATION

1. The Investigator submits the Continuing Review Application and all applicable documents to the CRC IRB for review including:
   • Consent/assent/information sheet
   • Recruitment/screening materials
   • Questionnaires, surveys, etc.
   • Progress reports
   • DSMB/Monitoring Reports
2. The IRB Coordinator conducts an administrative pre-review to check for missing or incomplete documents and for training requirements. Incomplete submissions are returned to the Principal Investigator (PI).
3. The IRB Coordinator enters the continuing review submission into the IRB tracking system.
4.  The IRB Coordinator assigns the Application to the appropriate IRB Analyst for review. The IRB Analyst and/or IRB Director will determine which IRB member will serve as the reviewer at the convened meeting.

REVIEW PROCESS

1. The IRB Reviewer and/or IRB Analyst will complete the appropriate Reviewer Worksheets and Approval Checklists.
2. The IRB Reviewer and all IRB members will have access to the following documents for the review, as applicable:
   • Continuing Review Application
   • Current consent form/statement
   • Recruitment/screening materials
   • Sponsor/NIH Progress reports
   • DSMB/Monitoring Reports
   • Questionnaires, surveys, etc.
3. The Continuing Review Application includes the following information:
   • The number of participants accrued
   • A summary since the last IRB review of:
     • Adverse events and adverse outcomes experienced by subjects
     • Unanticipated problems involving risks to subjects or others
     • Subject withdrawals
     • The reasons for withdrawals
     • Complaints about the research
     • Amendments or modifications
     • Any relevant recent literature
     • Any interim findings
     • Any relevant multi-center trial reports
     • The investigator’s current risk-potential benefit assessment based on study results
4. If the study is still open to enrollment, the IRB Reviewer will confirm that:
   • The current consent document is still accurate and complete
   • Any significant new findings are communicated to subjects who have already enrolled
5. The IRB must determine that the regulatory criteria for approval (45 CFR 46.111 and 21 CFR 56.111) are met. The criteria are defined below:
   • Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
   • 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. In evaluating risks and benefits, the Reviewer will consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research).
   • Selection of subjects is equitable. In making this assessment, the Reviewer will take into account the purposes of the research and the setting in which the research will be conducted. The IRB is particularly cognizant of the special problems of research that involves a category of subjects who are vulnerable to coercion or undue influence, such as children, prisoners, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons.
   • Informed consent will be sought from each prospective subject or the subject’s legally authorized representative.
   • Informed consent will be appropriately documented.
   • When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
   • When appropriate, there are adequate provisions 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, such as children, prisoners, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

LAPSE OF IRB APPROVAL
The IRB Coordinator sends out continuing review e-mail reminders to Principal Investigators approximately eight weeks and two weeks prior to expiration. Once the study expires, the IRB sends an e-mail to the Principal Investigator stating that the study is expired and that all research activities must stop. The expiration date is the last date that the protocol is approved.

Continued participation of already enrolled subjects may occur if:

• There is an over-riding safety concern or ethical issue such that the best interests of individual subjects are served by allowing these subjects to continue to participate in the research.
• There is the prospect of direct benefit.
• Withholding research interventions poses an increase risk to subjects.

If the Principal Investigator believes that it is in the best interest of already enrolled subjects to continue participation, he/she should submit a request to the IRB Director. The request should include the rationale for allowing continued participation of these subjects. The request will be reviewed by the IRB Director and/or IRB Chair. Consultants will be obtained as necessary. Enrollment of new subjects during the lapsed period will not be allowed.

If the Principal Investigator does not submit the Continuing Review Report 30 days after the protocol expiration date, the IRB will terminate the protocol. At this time, the IRB will notify the PI that the protocol has been terminated and that if the PI wishes to continue with the research, he/she must submit a new application to the IRB.

REVIEW PERIOD
Continuing review of research will be conducted at intervals appropriate to the degree of risk but not less than once per year (annually). The IRB may determine that continuing review must occur more frequently than annually. Continuing review may be required more frequently when:

• The research is high-risk
• The research involves novel treatment(s)/intervention(s)
• The PI has deviated/violated from IRB policies and/or federal regulations in the past
• The IRB Application required significant revisions
• The PI is new to research

CALCULATION OF APPROVAL DATE

Initial Approval: The date of initial approval is the date that all the required modifications/conditions are determined to be met. The date of expiration will be one year (minus one day) from the approval date unless the IRB determines that more frequent continuing review is necessary.

Continuing Review: For all subsequent continuing reviews, the CRC IRB follows a process for maintaining fixed anniversary dates for the expiration of IRB approvals when: 1) the IRB grants approval for one year at the time of each continuing review, and 2) the IRB performs continuing review and re-approves the research (all conditions/modifications must be met) within 30 days before the IRB approval period expires. If the research study is not submitted AND approved prior to the expiration date, the anniversary date will not be maintained. The new approval date will be the date that all the required modifications/conditions are determined to be met and the date of expiration will be date will be one year (minus one day) from the approval date unless the IRB determines that more frequent continuing review is necessary.

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Title: Continuing Review
Author: Cynthia Monahan
Effective Date: October 30, 2014
Last Review/Update Date: January 21, 2019
Revision #: 4
Approved: Cynthia Monahan, IRB Director
Kathryn Mellouk, Associate Vice President-Research Compliance