Presentation: Institutional Review Board: Compassionate and Emergency Use

(This presentation is also available in video format with captioning and PDF printer-friendly format.)

Presented by Fabienne Santel, MD

Division of Bioresearch Monitoring
Office of Compliance
Center for Devices and Radiological Health
Food and Drug Administration

Learning objectives

• Understand when an emergency need to use an unapproved device may occur
• Describe the role and responsibilities of the physician who wants to use the device on a patient for emergency or compassionate use
• Identify the IRB’s responsibilities in the compassionate use of an unapproved device

Emergency use of an unapproved device

• What is an emergency situation
• Physician’s role and responsibilities before and after emergency use
• Informed consent

Compassionate use of an unapproved device

• Describe what is meant by compassionate use
• The physician responsibilities with compassionate use
• The sponsor and the IRB’s role in compassionate use
• Practice

Emergency use of an unapproved device

Emergency use of an unapproved test article is not research

What is an emergency situation?

• All conditions must exist
  • Life-threatening disease or serious condition requiring immediate use
  • No generally accepted alternative for treating the condition is available
  • There is no time to use existing procedures to obtain FDA approval of an IDE.

When can a device be used in an emergency situation?

• There is no Investigational Device Exemption (IDE)
• Physician wants to use the device in a way not approved under an existing IDE
• A physician is not part of the IDE study

Physician’s role

• Determine whether the following conditions are met
  • Patient is in a life threatening situation
  • immediate use of the device is needed
  • no alternative
  • no time for FDA approval of an IDE
• Assess the potential for benefits from the unapproved use
• Have substantial reason to believe that benefits will exist

Physician’s responsibilities

• Physician should follow patient protection measures
  • Institutional clearance per institution policy
  • IRB chairperson concurrence
  • Authorization from the sponsor - if an IDE exists
• Independent assessment by a physician who is not participating in the investigation
• Informed consent from patient or legally authorized representative
  • Does not have to follow the informed consent requirements at 21 CFR 50.25
• What if there is no time to find an uninvolved physician? (21 CFR 50.23)
• The physician makes the determinations
  • Life threatening disease or condition
  • Immediate need
  • No alternative
  • No time for FDA approval of an IDE
  • Assessment of potential benefit
  • Substantial reason to believe benefit will occur
• The physician has his/her evaluation reviewed and evaluated in writing by an uninvolved physician
• Submit that report to IRB within 5 working days after the use
• What if No informed consent can be obtained? (21 CFR 50.23)
• The physician and a physician who is not participating in the clinical investigation must certify in writing ALL of the following:
  • Life-threatening situation necessitating the use of the device
  • No alternative therapy

Physician’s responsibilities after emergency use

• If an IDE exists, notify the sponsor
  • The sponsor must report to FDA
• If an IDE does not exist, notify FDA of the emergency use and provide FDA
  • a written summary of the emergency use,
  • patient protection measures, and
  • any scientific results
• Report to the IRB within five days and otherwise comply with IRB provisions
• Evaluate the likelihood of a similar need for the device
• If similar need is likely, obtain an IDE from FDA for the subsequent use and IRB approval

Compassionate use of an unapproved test article

• Single patient or small group use of an unapproved device

Compassionate use of an unapproved device

• Compassionate use is not research
• Unapproved device for serious disease or condition
• No alternative
• Patient does not meet inclusion criteria

Physician’s responsibilities

• A physician can use an unapproved device to treat, diagnose, or monitor a patient with a serious disease or condition
• The probable risk to the patient is not greater than the probable risk from the disease
• Physician requests authorization from sponsor
• Sponsor may agree or disagree
• The physician should not treat the patient until FDA concurs with the use
• Devise schedule for patient monitoring
• Address specific needs of the patient
• Detect possible problems
• Obtain independent assessment from uninvolved physician
• Obtain IRB chair’s concurrence
• Clearance from institution, if appropriate
• Obtain consent from the patient
• Report any problems as a result of the device use to the IRB and sponsor
• Write a summary of the use and give to sponsor

Sponsor responsibilities

• If sponsor disagrees with the use
  • The physician cannot use the device
• If sponsor authorizes the use
  • An IDE supplement is submitted to FDA requesting approval for a protocol deviation [21 CFR 812.35(a)].
• IDE Supplement
  • FDA’s concurrence is based on:
    information submitted; evidence that safety and effectiveness justifies the use; the use would not interfere with the conduct of a clinical trial to support marketing approval
• Prior FDA concurrence is required before compassionate use occurs

IRB and compassionate use

• IRB chair concurrence (documented)
• Ensure FDA concurrence
• Review consent document
• Receive reports after the use
• Receive reports of problems

Let’s put this into practice

• Interventional Cardiologist completed IDE study of a stent
• Continued to use the stent in his patients (>10) when he found coronary thrombosis. He declared this emergency use.

What would concern your IRB?

• On an FDA inspection, we found that a physician used an IDE device for compassionate use. There was no FDA or IRB concurrence.

How can an IRB help prevent this from happening?

• Approved biliary stent used in the carotid artery for carotid stenosis.
• Physician said he did this to treat his patient.

Is this emergency use or compassionate use or neither?

References for emergency use

• Regulation
  • 21 CFR 56.104(c)
  • 21 CFR 50.23
  • 21 CFR 812.35(a)(2)
  • 21 CFR 812.150(a)(4)
• Guidance
  • Federal Register/vol.50, No. 204/Tuesday, October 22, 1985
  • FDA Information Sheets

References for compassionate use

• Food, Drug, and Cosmetic Act
  •  Section 561 Expanded Access to Unapproved Therapies and Diagnostics
• Regulation
  • 21 CFR 812.35(a)
• Guidance
  •  www.fda.gov/cdrh/devadvice/
    type in “Expanded Access” and search

Key points

• Physicians can use unapproved devices in emergency situations
• IRBs must receive reports within five working days
• Subsequent emergency use-needs IDE
• Compassionate use requires prior FDA and IRB concurrence
• In compassionate use, IRB’s should: document their concurrence, ensure FDA concurrence, receive and review reports