REPORTING UNDER IND (PROTOCOL AMENDMENTS)
You need to submit an IND Protocol Amendment if you have either of the following changes during the course of your study:
- New protocol
- Change in protocol
- New investigator (new site)
The study may begin after you obtain IRB approval based on the new or amended protocol and after the FDA receives the amendment. FDA does not issue “permissions” or “approvals” for protocol amendments, your changes are effective immediately upon the receipt of your amendment by the FDA. The IRB may request documentation of FDA review of amendments and may hold approval until documentation is received from the FDA. In these cases, the PI must request that the FDA provide documentation that the research may continue. For changes in the protocol, the IND Protocol Amendment consists of:
- Cover Letter identifying the submission as “Protocol Amendment: Change in Protocol” or “Protocol Amendment: New Protocol”
- Form 1571 – Check an appropriate box under Paragraph 11, “Protocol Amendments”
- A document outlining the differences between the new protocol and the original protocol
For changes in the investigators, the IND Protocol Amendment consists of:
- Cover letter identifying the submission as “Protocol Amendment: New Investigator”
- Form 1571 – Check an appropriate box under Paragraph 11, “Protocol Amendments”
- Form 1572 for the new investigator
If there are manufacturing or other changes, such as:
- Changes in chemistry, manufacturing and control,
- Changes in pharmacology/toxicology (new findings affecting safety and efficacy), or
- Decision to discontinue a clinical study,
the manufacturer (in many cases, industry sponsor) will notify you. Your responsibility is to notify the IRB and make a decision as to whether to proceed with your trial.
REPORTING UNDER IDE (IDE SUPPLEMENTS)
Any changes in the Investigational Plan should be approved by the FDA and, when appropriate, IRB, prior to implementing any change to a previously accepted Investigational Plan. The following types of protocol changes would require an approved IDE Supplement, because they are likely to have a significant effect on the scientific soundness of the trial design and/ or validity of the data resulting from the trial.
- Change in indication
- Change in type or nature of study control
- Change in primary endpoint
- Change in method of statistical evaluation
- Early termination of the study (except for reasons related to patient safety) Change in the number of investigational sites
- Change in the number of study subjects
However, if the modifications meet certain criteria, the sponsor of an IDE may modify the device and/or clinical protocol without prior FDA approval. The sponsor still needs to provide notice to FDA within five working days of making the change. These notices must be identified as a “notice of IDE change.”
Emergency use: If PI deviates from the investigational plan to protect the life or physical well-being of a subject in an emergency. Such deviations should be reported to the IRB promptly after its occurrence, and to the FDA within five working days after the sponsor becomes aware of it.
Certain changes to the device: Advance IRB notification is not required if the changes do not constitute a significant change in design or basic operation and are made in response to information gathered during the course of an investigation. Examples include: creditable data generated under the device control procedures (21 CFR 820.30), preclinical/animal testing, peer reviewed published literature, and clinical information gathered during a clinical trial or marketing.
Certain clinical protocol changes: When they do not affect (i) the validity of the data or information resulting from the completion of the approved protocol, or the relationship of the likely patient risk to benefit ratio relied upon to approve the protocol; (ii) the scientific soundness of the investigational plan; or (iii) the rights, safety, or welfare of human subjects involved in the investigation.
If changes will be submitted in the annual report: A sponsor may make minor changes to an Investigational Plan without prior FDA approval; provided that the respective changes are reported in the annual progress report for the IDE (see Annual Reports).
Contact the Office for Research Protections Quality Assurance Program for assistance: orp-qm@psu.edu.