Office of Human Research
Page Title

SOP No.: 302    CLINICAL PROTOCOL AMENDMENTS

Author:    Office of Human Research

Effective Date:  October 1, 2007

Supercedes document dated:              N/A

Last Reviewed on:     N/A                                 

Results of Review:               N/A

This SOP pertains to:  All clinical protocol amendments that are developed for FDA-regulated human subject research by Investigators at the Thomas Jefferson University .

Responsibility for executing this SOP:  Investigator and Designated Research Personnel

Approved By:

 

J. Bruce Smith, MD

 

Associate Vice President for Research

 

(signature on file at OHR)

Approved By:

 

Steven E. McKenzie, MD, Ph.D.

 

Vice President for Research

 

(signature on file at OHR)

 

1. PURPOSE

This procedure describes the process for developing, reviewing and approving protocol amendments that will be used for conducting a clinical study intended to collect safety and/or efficacy data on an unapproved use of a new drug, biologic or medical device (the investigational product).

2. GENERAL INSTRUCTIONS AND RESPONSIBILITIES

  1. The Investigator or qualified designee is responsible for preparing the initial draft of the protocol amendment and forwarding the draft to all designated individuals for review and approval, for modifying protocol case report forms (CRFs) and informed consent forms (ICFs) (distributing final IRB-approved amended protocols, revised CRFs and ICFs to all Investigators at all sites.
  2. The Investigator is responsible for forwarding final, approved protocol amendments to the FDA (alone or as part of another document) and other regulatory authorities, for their review and approval as appropriate and necessary.
  3. All Investigators are responsible for obtaining local Institutional Review Board (IRB) approval and if applicable, Institutional Biosafety Committee (IBC) and other internal and external regulatory approvals before implementing the protocol amendment.
  4. A protocol change to eliminate an immediate hazard to participants may be implemented immediately provided the FDA and the IRB are notified as soon as possible afterwards, but no more than 5 days after the change is implemented.
  5. In many cases, changes to a protocol will result in necessary changes to the informed consent form.

3. SPECIFIC PROCEDURES

3.1 Writing Protocol Amendments

  1. Minor changes (as defined below and by the FDA) can be made to the protocol and related documents provided they do not affect the study design. Such changes include editorial changes, correcting typographical errors, and appropriate scientific or technical clarifications.
  2. These minor changes must be documented on the protocol's Table of Modifications and approved by the Investigator. They are incorporated into the protocol at the time of the next protocol amendment submission.
  3. The FDA also permits modifications to the experimental design of phase I protocols that do not affect critical safety assessments to be reported to the FDA only in annual reports.
  4. Amendments to a protocol will be numbered sequentially and consistently throughout the study conduct period.
  5. The designated Author of the protocol amendment, or his/her designee, will prepare the first amendment draft.
  6. The Author will prepare the amendment using a strikeout and highlight-editing program such that all deleted text is marked as strikeout and all new text is highlighted.
  7. A cover memo that outlines each change (all deletions and all additions) to the protocol will be prepared by the Author and attached to the front of the amendment.
  8. The Author will also prepare the Document Control Form and attach it to the draft amendment. The document is labeled with the appropriate version date (See SOP 102 Attachment A).

3.2 Amendment Review and Approval

  1. The suggested amendment to the protocol will be reviewed and approved by all individuals designated by the Investigator and the Author (Reference SOP 102, Document Development and Change Control for a controlled document).
  2. The Author will circulate the appropriately identified protocol amendment draft to all designated individuals and other experts to ensure it is scientifically and ethically sound, and meets all applicable regulations and guidelines.
  3. The Author will repeat the review process until all comments are addressed as necessary.
  4. The final draft protocol amendment must be reviewed and approved by signature and date of all designated individuals.
  5. Once reviewed and approved, the Author will add the proper amendment number (e.g., Protocol 1234-01) and effective date (corresponding to the date of the final approval signature) (See SOP 102 Attachment A).
  6. A clean copy of the final amendment should be obtained by the Investigator for approval and signature.
  7. Protocol amendments must be submitted to the IRB and FDA when any revisions are made to the original protocol or subsequent version of the protocol that significantly affects the safety of participants and/or any change is made that significantly affects the scope of investigation or scientific quality of the study.
  8. Participating Investigator(s) at each site are responsible for submitting a clean copy of the amended protocol and amended informed consent form (where appropriate), and a memo that outlines the deletions and additions to the protocol to the local IRB of record, and other regulatory authorities where applicable, e.g., IBC.
  9. A protocol amendment cannot be implemented until the protocol has been submitted to FDA for review and it has been approved by the IRB (and other regulatory authorities, e.g., IBC, if necessary).
  10. Once final local IRB approval is obtained, the Investigator should obtain a copy of the IRB approval letter.
  11. The protocol amendment submission should be prepared as follows:
    • Cover letter or summary page describing the changes made to the previous version of the protocol and referencing the original submission
    • A copy of the amended protocol in which the deleted text is marked as strikeout and all new text is highlighted
    • A clean copy of the new clinical protocol amendment
    • A copy of the IRB approval letter or certifications of IRB action (if applicable)
    • If comments are desired from the FDA on the protocol amendment, a request for this is included in the submission
    • The protocol amendment may not be implemented until final IRB approval is obtained; the amendment has been submitted to the FDA.
  12. The Investigator will forward a copy of the final IRB-approved and the FDA-submitted protocol to the Office of Human Research, all Investigators in the study and all appropriate clinical study staff at Thomas Jefferson University.
  13. The Investigator and other participating Investigators must sign the signature page of the protocol, indicating that they understand and agree to the changes. The participating Investigator will retain a copy of the signed protocol in his/her files, and return the original signed signature page to the Investigator.
  14. The Investigator is responsible for training his/her staff of the changes to the protocol. For studies conducted at Thomas Jefferson University, the Investigator will ensure that relevant key study personnel are trained on the changes to the protocol.

4. ATTACHMENTS

None

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