1. In order for a HUD to be used in treatment or diagnosis at UIC or JBVAMC, the HUD must have an approved HDE from the FDA and IRB approval.  FDA regulations and UIC HSPP require initial IRB review and approval at a convened meeting. Emergency and compassionate use of a HUD may be allowed in accordance with FDA regulations and UIC HSPP policy.   
2. Informed consent is not required by FDA regulations when a HUD is used for an approved indication, unless the use represents a clinical investigation.  However, the UIC IRBs invoke their regulatory discretion in this circumstance and require documented informed consent.  In lieu of the UIC HUD informed consent template, the health care practitioner (investigator) may request the use of an alternative format, e.g., substitution of the FDA approved patient information packet for some of the required sections of the UIC HUD consent template.
3. Collection of safety and effectiveness data to support a premarket approval (PMA) application by the HDE- holder for the HDE-approved indication may occur under the HDE without the need to obtain an Investigational Device Exemption (IDE).  However, the activity is considered a clinical investigation (i.e., research) rather than clinical practice and, as with other FDA-regulated clinical investigations, IRB approval and informed consent are required.  Also, since the clinical investigation is considered research, authorization from the subject or LAR under the HIPAA Privacy Rule is required for protected health information to be used or disclosed.
4. Off-label (i.e., use for a non-HDE approved indication) use of the HUD requires review and approval by the convened IRB on a case by case basis, except for emergency or compassionate use.  IRB approval for the HDE-approved indication must also occur before the off-label is reviewed. If the off-label use is part of a clinical investigation, procedures should follow those described in the UIC policy, “Research Involving the Use of Drugs, Biologics or Medical Devices”, including securing an IDE.

1. The health care practitioner (investigator) is required to submit the following
   materials to the IRB for review and approval of the use of a HUD:
   1. UIC HUD application;
   2. FDA HDE approval order (a list of approved HDEs along with the approval
      order, summary of safety and probably benefit, labeling and patient
      information);
   3. Professional labeling;
   4. Summary of safety and probable benefit;
   5. Device manual or brochure (if available);
   6. Patient labeling/Information Packet (if available);
   7. Protocol (if available);
   8. Consent form for use of the HUD.

      The entire board receives copies of items A, F and H, while all items are provided
      to the primary reviewers. All IRB members have access to the complete protocol
      file, containing items A through H.

2. Consent for Clinical Use of the HUD.
   1. Informed consent and documentation of informed consent is required when
      treating or diagnosing a patient with a HUD.
   2. The format, required sections and recommended language for the HUD
      consent for clinical use are provided on the UIC HUD consent template.
   3. When FDA-approved patient information labeling or packet is available, this
      document may substitute for certain required sections of the UIC consent,
      including “Why does my doctor want to use this …”, “What will be involved
      with use of the HUD”, “Risks”, “Benefits”, and “Alternative.”
3. When available, any FDA-approved patient labeling information prepared by the
   manufacturer is to be provided and reviewed with the patient prior to use of the HUD
   regardless of whether it is being used as part of the consent process. The plan for
   how this will be conducted is to be described in the UIC HUD application.
4. Initial IRB Review of a HUD.
   1. Initial review of a HUD is performed at a convened meeting of the IRB.
   2. IRB reviews the material listed in I. in making their determination.
   3. IRB review and approval of the HUD request follows the review criteria at 21
      CFR 56.111 as much as possible, including:
      1. Evaluating the risks described in the product labeling and ensuring the
         risks are minimized,
      2. Ensuring risks are reasonable in relation to the anticipated benefits of
         the proposed use of the device,
      3. Ensuring informed consent is obtained from each prospective patient or
         their legally authorized representative,
      4. Ensuring informed consent is appropriately documented, and
      5. Where appropriate the plan for use of the HUD adequately monitors
         the safety of subjects.
   4. IRB must verify that proposed use of HUD corresponds with the current
      labeling and does not exceed the scope of the FDA-approved indication.
   5. The IRB evaluates whether the health care provider(s) is qualified through
      training and expertise to use the device.
   6. The IRB may approve use of the HUD without any restrictions beyond the
      FDA-approved labeling or may impose more stringent criteria for use of the
      HUD as deemed necessary to provide additional protections.
   7. IRB determines the continuing review frequency (i.e., at least annually) and
      whether it may occur by expedited procedures.
   8. The IRB’s determination is documented in the meeting minutes.
   9. Use of the HUD should be restricted to personnel listed on the HUD
      application reviewed and approved by the IRB.
   10. The HUD must be stored in a secure manner and labeled appropriately to
       prevent the use by unapproved personnel or the use of the device in an
       unapproved manner.
5. Continuing IRB Review of a HUD.
   1. The IRB will conduct a continuing review of the use of the HUD at intervals
      appropriate to the degree of risk, but no less than once a year.
   2. Continuing review may be performed by expedited procedures by the IRB
      Chair or member designated by the Chair.
   3. Continuing review of the HUD should follow UIC Continuing review policy.
      HUD-specific information that should be provided the IRB reviewer includes:
      1. Number of times the HUD has been used,
      2. Any problems associated with its use,
      3. Unanticipated problems, including serious adverse events and
         deviations since the last review.
      4. Any use outside of the FDA approved labeling or emergency use,
      5. Any information provided to the sponsor or FDA concerning use at
         Other sites or any annual reports to the FDA, and
      6. Any Medical Device Reporting reports or UIC Prompt Reporting
         reports.
6. Modifications to the HUD or proposed changes to the clinical use of the device must
   be submitted for IRB review and approval using the UIC Amendment application.
   The amendment application should be accompanied by 1). the FDA’s approval of the
   modification, 2). the HDE holder’s amendments to the HUD product labeling, clinical
   brochure, and/or other pertinent materials corresponding to the requested
   modification(s), and 3). the revised clinical consent form with the modifications
   indicated. .
7. Collection of Safety and Effectiveness Data when HUD is used in Accordance
   with its Approved Indication(s).
   1. Collection of safety and effectiveness data to support a PMA application by
      the HDE-holder for the HDE-approved indication may occur under the HDE
      without the need to obtain an Investigational Device Exemption (IDE).
   2. This activity is considered by the FDA to represent a clinical investigation (i.e.,
      research) and, as with other FDA-regulated clinical studies, IRB approval and
      informed consent are required.
   3. The investigator should submit the materials described in I. for IRB review and
      approval.
   4. The investigator must also complete and submit the additional sections on the
      HUD application and Consent Form designated for completion when safety
      and effectiveness data are being collected for an FDA-regulated clinical
      investigation or other research activity.
   5. Also, since the activity is now considered research, authorization from the
      patient (or waiver of authorization) under the HIPAA Privacy Rule is required
      for protected health information to be used or disclosed. HIPAA authorization
      language is incorporated into the UIC HUD consent form.
   6. Initial and continuing review by the IRB will follow the criteria in the UIC Initial
      and Continuing Review Biomedical Review Guide along with the criteria
      outlined for the clinical use of a HUD in sections IV and V.
   7. Even when the data will not be submitted to the FDA, the collection of safety
      and efficacy related to use of the HUD for its approved indication by the
      investigator for activities meeting the OHRP or FDA definition of human
      subject research (see UIC HSPP policy Institutional Authorization for
      Determining whether Research or Other Activities Represent Human Subjects
      Research) must follow the additional submission and review requirements
      described here for those activities representing FDA-regulated studies.
8. Considerations for Prompt Reporting.
   1. Whenever the physician or health care provider primarily responsible for use
      of the HUD at UIC becomes aware of information, from any source, that
      reasonably suggest that a HUD has or may have caused or contributed to the
      death or serious injury of a patient, the physician or health care provider must
      report such findings to the FDA and the UIC IRB as soon as possible, but no
      later than 10 working days after the Investigator first learns of the effect or
      problem. The UIC Prompt Reporting Form should be used to submit this
      information to the IRB.
   2. The reporting requirements outlined in the UIC HSPP policy Unanticipated
      Problems and Other Events Requiring Prompt Reporting, should be adhered
      to with the use of the HUD.
   3. The health care practitioner responsible for use of the HUD shall report any
      FDA actions regarding the HUD to the IRB within 10 working days of being
      notified.
9. Use of a HUD in an Emergency. The HUD may be used off-label (i.e., a nonapproved
   indication) or without prior IRB approval in an emergency situation. The
   UIC Policy on “Emergency Use of Test Article” must be followed, including obtaining
   concurrence of the IRB chair or designee, informed consent from subject or legally
   authorized representative, independent assessment from a uninvolved physician and
   authorization from the HDE holder.
10. Compassionate Use of HUD. The FDA allows the use of a HUD in circumstances
    where the device is the only option available for a patient faced with a serious or lifethreatening
    condition that does not meet the criteria of an emergency. A use is
    commonly referred to as “compassionate use”. Unlike emergency use, prior FDA
    approval is required before compassionate use occurs. As a first step, the clinician
    should seek the approval of the HDE holder and provide them with the following
    information: 1). description of the patient’s condition and circumstances
    necessitating, 2). discussion of why alternative therapies are unsatisfactory, an
    identification of any deviations from the approved HUD labeling required to treat the
    patient and patient protection measures that will be followed. The HDE holder must
    then submit an IDE(HDE) supplement to the FDA for approval. Once FDA approval
    is obtained, the investigator should submit the materials listed in I. along with
    documentation of FDA approval of the compassionate use to the IRB for review and
    approval.

21 CFR 814 subpart H
21 CFR 803.30
21 CFR 814.124(a)
21 CFR 812.35
FDA Guidance: Draft Guidance for HDE Holders, IRBs, Clinical Investigators, and FDA
Staff – HDE Exemption Regulation: Questions and Answers, dated August 5, 2008