New York University Langone Medical Center/School of Medicine
Institutional Review Board
Continuing Education
Amendments
February 2009
Definition of Amendments
An amendment is defined by the regulations as any change to a research activity during the time the project has IRB
approval. Changes may not be initiated by the research team prior to this action except when necessary to eliminate
apparent harm or immediate hazards to the subject. The IRB has the authority to approve, modify or disapprove any or
all changes to the study
Types of amendments
There are three (3) different types of revisions: informational, minor and major. Informational revisions are generally
editorial changes such as changes in telephone numbers, addition or deletion of study staff, or change of study location
site. These changes are reviewed in an expedited manner by a designee of the board. Minor changes are changes that
may impact the research subjects but do not impact the risk to the subjects. Examples include, adding nonsensitive
questions to a questionnaire, adding no more than 10% to the subject population, changing contact information on the
consent form or consent form formatting. Minor revisions are reviewed by the IRB Board staff.
Major changes impact the risk to subjects. Examples include: Increase in the study drug dosage, addition of a research
arm of the study, or additional study medications or devices. These amendments are pre-reviewed by the board research
analysts for review by the full board at a convened meeting.
The key determining factor is that minor revisions will fall within the federal regulatory definition of minimal risk.
How is an Amendment submitted?
Principal Investigators are required to provide the following information for review: (1) completed Application for
Approval of Amendment; (2) revised Investigator’s protocol or sponsor’s protocol or most current protocol (if the
changeis major mdofication) ; (3) revised approved consent form/parental permission/assent documents or other
documentation that would be provided to subjects when such information might relate to their willingness to
continue to participate in the study; and (4) any information justifying the modifications.
How should you review this information? AND what questions should you should be asking to make the
amendment determination?
First, ensure you have all the completed documentation required to proceed with your review. If anything is missing,
please contact the IRB office right away. IRB members are required to review changes at a full board meeting that
affect the 45 CFR 46.111 determinations.
As with new studies the IRB must make 45 CFR 46.111 findings at the time of approving modified research. In
order to ensure the research study continues to meet the regulatory criteria required under 45 CFR46.111 a
reviewer should evaluate:
For an Amendment Review to be approved all the 111 criteria must still be met.
(1) Risks to subjects are minimized. Does the change increase the risks to subjects? Are risks
now minimized than previously?
(2) Anticipated benefits are reasonable. Are benefits affected by this change?
(3) Selection of subjects is equitable – Is the inclusion/exclusion criteria different? Does change in
exclusion/inclusion affect equitable criteria?
(4) Informed consent will be sought from each prospective subject – does amendment disqualify waiver
of consent?
(5) Informed consent will be appropriately documented – does amendment disqualify waiver
of documentation?
(6) When appropriate, the research plan makes adequate provision for monitoring the data collected to
ensure the safety of subjects. Was the monitoring procedure changed? Does it protect subjects?
(7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the
confidentiality of data. Is the PI requesting access to additional data?
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The following information should be included for a thorough review to be completed:
(1) Revision justification- Has the researcher provided written documentation of the reason for the revision? How
will the revision impact the risk/benefit ratio? What safeguards have been implemented to protect subjects from
additional risks?
(2) New information– If new information is made available requiring a change, does it affect the most recently
risk/benefit ratio determination? Is there a need for a DSMB? Are any additional changes needed to enhance
safety? Has or will this information be conveyed to enrolled subjects and how?
(3) Revised protocol, consent document, recruitment materials, etc. – Are all revised documents consistent with the
amendment?
(4) Addition of Vulnerable Populations- Sub-part determinations are needed for the required population. Are any
additional protections necessary that are not included?
What if something is missing and you cannot complete your review or make a determination of one of the
findings?
Communicate and contact the IRB Office first to make sure that you have received all the necessary documents. If
you have all the documents submitted and are still unable to complete your review, contact the Principal
Investigator directly. This will ensure all appropriate and accurate information is reviewed. Communicate with the
IRB office board staff regarding communications/changes made to ensure all documentation is received and
retained. Remember if one of the 111 findings cannot be determined, the project may not be approved.
Your review is complete, how do you present your review at the meeting?
State what action is appropriate for the amendment. For example, this amendment should be granted approval.
This project may be approved by the following 45 CFR 46 determinations: PRESENT DETAILED EVIDENCE……
You will need to ensure that none of the previous 111 findings have been affected by the amendment or if they
have – how which finding is affected and how does that change the overall 111 findings decision.
For vulnerable populations, ensure Sub-part determinations have also not been changed if included already. This
information must be verbalized at the meeting for inclusion in the minutes to stay in compliance with the
regulations. Ensure that the research review intervals do not need to be changed.
You are a researcher and an IRB member. From what point of view should you be reviewing?
As an IRB member you are in the position as evaluator of the study. This will assist in your understanding of
boundaries and time constraints. Sometimes we forget our roles as IRB members by reviewing in the researcher’s
perspective. This happens especially when members are researchers themselves.
When in doubt, remember where the information is:
*Application for Approval of an Amendment and Reviewer’s Checklist =111 Findings*
OR
Call the Principal Investigator/Research Team or IRB office if you need more information or
have any questions. If all questions are cleared before the meeting a continuation review will
more than likely lead to approval!
References:
IRB Member Handbook (Second Edition)- Amdur and Bankert
45 CFR 46
IRB New Member Orientation Power Point
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