IDE Process: 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, and
• early termination of the study (except for reasons related to patient safety).
In addition, FDA believes that expanding the study by increasing either the number of investigational sites or the number of study subjects participating in a clinical investigation affects the rights, safety, and welfare of the subjects. Therefore, the study may not be expanded without submission and approval of an IDE supplement.
The IDE supplement should be identified with the IDE number on the cover sheet and submitted in triplicate. The outside wrapper of the submission should identify the contents as "Supplemental IDE."
Some exceptions from prior IRB and FDA approval are allowed in the following circumstances:
1. 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 5-working days after the sponsor becomes aware of it.
2. Certain changes to the device. Advanced 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 Sec. 820.30), preclinical/animal testing, peer reviewed published literature, and clinical information gathered during a clinical trial or marketing. For a developmental or manufacturing change to a device, the “Notice of IDE Change” shall include:
- a summary of the relevant information gathered during the course of the investigation upon which the change was based;
- a description of the change to the device or manufacturing process (i.e., cross-referenced to the appropriate sections of the original device description or manufacturing process); and
- if design controls were used to assess the change, a statement that no new risks were identified by appropriate risk analysis and that the verification and validation testing, as appropriate, demonstrated that the design outputs met the design input requirements. If another method of assessment was used, the Notice shall include a summary of the information, which served as the creditable information supporting the change.
3. Certain clinical protocol changes that 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. For a clinical protocol change, the “Notice of IDE Change” need to include:
- a description of the change (cross-referenced to the appropriate sections of the original protocol);
- an assessment supporting the conclusion that the change does not have a significant impact on the study design or planned statistical analysis; and
- a summary of the information that served as the creditable information supporting the sponsor’s determination that the change does not affect the rights, safety, or welfare of the subjects.
4. 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 Progress Reports). These minor changes to the purpose of the study, risk analysis, monitoring procedures, labeling, informed consent materials, and IRB information may 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