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IDE Modifications

A sponsor may need to obtain approval from CPHS and the FDA prior to implementing a change to an investigational plan.

1. Changes in investigational plan that require prior approval (21 CFR 812.35).

The following types of protocol changes require an approved IDE supplement because the FDA believes that they are likely to have a significant effect on the scientific soundness of the trial design and/or the 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)

The FDA also believes that expanding the study by increasing either the number of investigational sites or number of study subjects affects the rights, safety, and welfare of subjects. Therefore, these actions also require approval before implementation.

The IDE supplement must be identified by IDE number on the cover sheet and submitted in triplicate. The outside covering of the submission should identify it as "Supplement IDE."

2. Changes in the investigational plan that do not require prior FDA approval:

Notice of the following modifications to the device and/or investigational plan must be provided to the FDA within 5 working days of making the change:

  • Emergency Use
  • Certain Developmental Changes
    • An FDA-approved supplement is not required for developmental changes in the device, including manufacturing changes, that do not constitute a significant change in design or basic principles of operation and that are made in response to information gathered during the course of the clinical investigation. Credible information to support developmental changes in the device includes data generated under design control procedures (see 21 CFR 812.30), preclinical/animal testing, peer reviewed published literature, or other reliable information such as clinical information gathered during the trial or marketing. Generic types of device and manufacturing changes include changes to the control mechanism, principle of operation, energy type, environmental specifications, performance specification, ergonomics of patient-user interface, dimensional specifications, software or firmware, packaging or expiration dating, sterilization, and manufacturing process (including the manufacturing site).
    • All developmental changes need to be reported to theCPHS in the sponsor's annual report. Changes may also be subject to CPHS review when they are made.
  • Certain changes to the clinical protocol
    • An FDA-approved supplement is not required for changes to clinical protocols that do not affect:
      • Validity of the data or information in the approved protocol, or the subject risk-to-benefit relationship relied upon to approve the protocol.
      • Scientific soundness of the investigational plan
      • Rights, safety, or welfare of human subjects involved in the investigation.
    • The determination is made by the sponsor and must be based on credible information. Examples of such changes include:
      • Modification of inclusion/exclusion criteria to better define the arget subject population
      • Increasing the frequency at which data or information is gathered
      • Inclusion of additional patient observations or measurements
      • Modifying the secondary endpoints (which usually support a secondary labeling claim and are not used to determine the safety or effectiveness of the device).
    • For a protocol change, the notice to the FDA within 5 working days of the change must include
      • Description of the change ("track changes" version of the document)
      • Assessment supporting the conclusion that the change does not have a significant impact on the study design or planned statistical analysis
      • Summary of the information that served as credible information supporting the sponsor??s determination that the change did not affect the rights, safety, and welfare of the subjects.

3. Changes to be submitted in the annual progress report

Minor changes in the following areas (which do not meet the criteria listed above in the section for changes that must be submitted for FDA approval prior to augmentation) may be reported in the annual progress report:

  • Purpose of the study
  • Risk analysis
  • Monitoring procedures
  • Labeling
  • Informed consent materials
  • CPHS information
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