II.13

 

 

Review of Modifications/Amendments to Previously Approved Research

 

 

Objective

The Committee for the Protection of Human Subjects (CPHS) reviews all requests for modification/amendments to previously approved research, and this Policy/Procedure describes the process by which the CPHS reviews modification/amendments submitted for approval.

 

Policy/Procedure

I.      The Principal Investigator (PI) must receive approval from the CPHS before initiating any changes, including those required by the sponsor, which would affect human subjects, e.g. changes in methods or procedures, numbers or kinds of human subjects, early termination of study, or revisions to the informed consent document or procedures.  The addition of co-investigators must also receive approval from the CPHS.  An investigator may not implement any modifications/amendments to research without prior approval by the CPHS, except to avert or minimize apparent immediate hazard to the participant. Such action must be promptly reported to the CPHS for review and approval

 

II.    The PI must submit the modification/amendment via the Internet Research Information System (iRIS).

 

A.   The exact text changes of an amendment may be incorporated into a revised version of the protocol or other document.

1.     Modifications to the informed consent form (ICF) should take into account both prospective research participants and research participants already enrolled in the study.  New findings developed during the course of the research which may affect a participantŐs willingness to continue participation must be provided to the participant in a letter of notification, an addendum to the initial consent document, or by re-consenting the participant using the modified ICF.  All such revised documents must be approved by the CPHS.

 

B.    Modification/amendment to research involving prisoners must go to the full committee for review.

 

C.    For research that was initially determined to be exempt, any proposed or anticipated changes must be submitted to the CPHS for approval prior to initiation of the change. The research proposal will then be evaluated for appropriate IRB review, as defined in Policy and Procedure 16.


D.   For those modifications to research that are identified as qualifying for expedited review:

 

1.     The IRB coordinator shall assign the requested modification to an Expedited Reviewer (Reviewer). All previous information regarding the research is in iRIS for the Reviewer to access.

2.     If the Reviewer determines that the modification does not qualify for expedited review, the request shall be returned to the IRB Coordinator to be assigned to the full committee to review and take action on.

3.     The Reviewer shall review the modification/amendment

4.     The Reviewer will take the following actions on the requested modification/amendment:

a)     Approve

b)    Approve pending modifications

c)     The reviewer may not disapprove the change, but instead return the request to the IRB coordinator to be assigned to a full committee for review.

5.     All modifications approved by expedited review (minor changes) must be reported to CPHS   #1 & #2 by placing them on the next agenda.

 

E.    For those modifications that must go to a full convened meeting:

1.     The IRB coordinator shall determine the chairman of the subcommittee that initially reviewed the study and assign it to that person (or to one of the other subcommittee members if possible, if the chairman is not available) as the Primary Reviewer.  A Reviewer must declare any Conflict of Interest with the research assigned to him/her for review.  If there is a conflict, the research study shall be reassigned to another Reviewer.

2.     The assigned Primary Reviewer and all members of the CPHS shall be provided the request for modification and all supplemental information via iRIS. Members of the CPHS are expected to have knowledge of the full protocol, consents, and recruitment materials.  All previous information regarding the research is in iRIS for the members to access to determine whether the modified research continues to fulfill the regulatory criteria for approval.

3.     The Primary Reviewer shall review the requested modifications/amendments and shall indicate any issues/clarification and make a recommendation to the committee..

4.     After receiving the information and recommendation the CPHS shall review and discuss the request.

5.     Should the ICF require revision the CPHS may request that participants currently in the study be reconsented. Should this request be made it shall be included as a provision in the approval letter to the PI.

6.     The CPHS shall determine whether participants who have completed research involvement might be affected, and/ or might need to be recontacted and provided with additional information. This determination should be based on new information regarding a change to the risk/benefit ratio that would possibly affect the participantŐs welfare. Should it be determined that the participants must be recontacted, it shall be a provision in the approval letter to the PI.

7.     When the CPHS reviews a modification request that involves prisoners, at least one voting member must be present at the CPHS meeting who is a prisoner, or a prisoner representative with appropriate background and experience to serve in that capacity.

 

8.  Changes made to a protocol in order to address an immediate hazard to study participants must be reported to CPHS in a timely manner, via a change request and a protocol deviation.  CPHS will then determine whether changes are consistent with continued participation in the study. 

 

F.    The proposed modification shall have one of the following actions taken.

                       

                       

1.  Approval of the modification

 

2.  Approval Pending Stipulations

 

3.  Defer pending receipt of additional information

 

4.  Disapproval

 

1.     Approved:  An approval is grant if the research activity meets the criteria for approval as defined in 45 CFR 46.111 and no changes are recommended to the modification. The investigator will receive a written notice of approval via iRIS.

 

2.     Approval Pending Stipulations: An approved pending status if given if the research meets the 45 CFR 46.111 criteria for research approval and any modifications required by the IRB require simple concurrence by the investigator.  When the modifications requiring simple concurrence are received from the investigator, the Chair or his/her designee may then review and confirm the modifications through an expedited procedure.  The proposal may be referred back to the full committee if deemed necessary by the Chair or his/her designee.  The investigator will receive a written request for modifications via iRIS.

 

3.     Defer pending receipt of additional information:  When the convened board requests substantive modifications or clarifications directly relevant to the determinations required at 45 CFR 46.111, IRB approval of the proposed modification is deferred, pending subsequent review by the convened board of responsive material.  The investigator will receive a written request for specific or additional information required via iRIS.

 

4.     Disapproval:  Disapproval is given if the modification does not meet the criteria for approval as defined in 45 CFR 46.111 (refer to section II above).  If the IRB decides to disapprove a research activity, it shall include in its written notification a statement of the reasons for its decision via iRIS and give the investigator an opportunity to respond in person or in writing.

 

5.  Table: A  modification may be tabled until another meeting due to lack of review.  In the event of a loss of quorum, all incomplete agenda items shall be considered tabled until quorum can be reconstituted in a convened meeting.

 

III.  The approval date of the protocol modification is the date of the meeting at which the CPHS approved the modification.

 

IV. The decisions and possible requirements for changes requested by CPHS are promptly conveyed to the PI in iRIS.

 

Applicable Regulations and Guidelines

21CFR 50 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/21cfr50_04.html )

21CFR 56( http://www.access.gpo.gov/nara/cfr/waisidx_04/21cfr56_04.html )

38CFR 16 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/38cfr16_04.html )

45CFR 46 ( http://www.access.gpo.gov/nara/cfr/waisidx_04/45cfr46_04.html )

ICH E6 ( http://www.ich.org/MediaServer.jser?@_ID=482&@_MODE=GLB )

AAHRP Evaluation Instrument for Site Visitors ( http://www.aahrpp.org/Documents/D000043.PDF )

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