Transcript CUMC PPT Tutorial File

CUMC IRB Investigator Meeting
Special IND/IDE Considerations:
Emergency Use of Investigational Product
Compassionate Use
& Emergency Research
July 21, 2005
Objectives
Today’s session will provide information on:
• Understanding of Regulatory Requirements and
Considerations
• Understanding the Options of Treating Patients with
Experimental Therapies
• How to Prepare an Application to the IRB for Emergency
Research
• How to Conduct Community Consultation
July 21, 2005
Page 2
FDA Regulations
Code of Federal Regulations:
-Title 21, Parts 50.23
-Title 21 CFR 50.24
-Title 21 CFR 312
-Title 21 CFR 812
Guidance:
-Humanitarian Use Device Exemptions
-Guidance on IDE Policies and Procedures
July 21, 2005
Page 3
Federal Regulations for the Protection of Subjects from Research Risks
45 CFR Part 46
Subpart A -- Basic Protections
Subpart B -- Pregnant Women, Neonates and Fetuses
Subpart C -- Prisoners
Subpart D -- Children
July 21, 2005
Page 4
Emergency Use
of an
Investigational Drug or Device
July 21, 2005
Page 5
Emergency Use of an Investigational Drug or Device
-Medical care with investigational product, not research
-Only allowed in emergency, life-threatening situations, when:
-no alternative standard treatment is available
-another physician concurs with the assessment that the
situation is life-threatening and no alternative std. tx is
available
-all efforts should be made to obtain informed consent
-Allowed for ONE time use; subsequent use requires Prospective IRB
Approval (CAUTION: Trigger for FDA Audit)
July 21, 2005
Page 6
Emergency Use of an Investigational Drug or Device
-Distinction between life-threatening and site-threatening
-Site threatening (i.e., loss of organ) may be allowed
-Should always consult with sponsor (i.e., IND/IDE holder) prior to use
of the product in a life-threatening situation
-Data may not be used for research purposes
July 21, 2005
Page 7
Emergency Use of an Investigational Drug or Device
-Sponsor or Pharmacy may request approval from the IRB
-IRB will not approve, but will provide authorization letter in accordance
with 56.104 and 50.23;
-IRB authorization letter should be generated within 3 hours upon
submission of all necessary information;
-patient’s initials;
-drug or device name;
-patient’s diagnosis/indication for drug or device
July 21, 2005
Page 8
Emergency Use of an Investigational Drug or Device
After use of the drug or device:
Within 5 days, must submit the following to the IRB (by letter, not in
RASCAL):
-documentation that the case was a life-threatening situtation;
-concurrence of another physician;
-whether or not informed consent was obtained; and if not, what efforts
were made to obtain consent;
-submit protocol and consent form to the IRB for review if there is any
expectation of a future use of the drug or device.
July 21, 2005
Page 9
Compassionate Use
with an
Investigational Drug or Device
July 21, 2005
Page 10
Compassionate Use of an Investigational Drug or Device
-Generally, intent of providing therapy or treatment to a patient that
would not be available in standard practice AND the subject does not
qualify for a research study;
-Generally, does not fit the emergency, life-threatening criteria.
July 21, 2005
Page 11
Compassionate Use of an Investigational Drug or Device
-Needs prospective IRB approval and therefore needs a submission in
RASCAL;
-Needs informed consent obtained in accordance with IRB requirements;
-Should have a sponsor’s protocol and investigator’s brochure attached;
-Should clearly state that the effort is primarily compassionate use and not
research and state if time is of the essence.
July 21, 2005
Page 12
Compassionate Use of an Investigational Device
Some flexibilities are offered by FDA guidances on devices:
Humanitarian Device Exemption Regulation: Questions and Answers: Final
Guidance for Industry (July 12, 2001)
http://www.fda.gov/cdrh/ode/guidance/1381.html
Guidance on IDE Policies and Procedures (January 20, 1998)
http://www.fda.gov/cdrh/ode/idepolcy.html
July 21, 2005
Page 13
Compassionate Use of an Investigational Device
Flexibilities Offered
Humanitarian Device Exemption Regulation: Questions and Answers: Final
Guidance for Industry (July 12, 2001)
-HUD may be used for compassionate use;
-Consult with sponsor/IDE holder;
-Physician should ensure patient protection measures are addressed;
-If Research, then submit application in RASCAL;
-If Medical Care w/o Research, submit a letter to the IRB (consult with
IRB first)
-Prior FDA approval is required.
July 21, 2005
Page 14
Compassionate Use of an Investigational Device
Flexibilities Offered
Guidance on IDE Policies and Procedures (January 20, 1998) – Chapter III,
Expanded Access to Unapproved Devices:
Individual Patient Access to Investigational Devices Intended for Serious
Diseases (falls under 812.35 Supplemental Applications):
-Consult with sponsor/IDE holder;
-Physician should ensure patient protection measures are addressed;
-If Research, then submit application in RASCAL;
-If Medical Care w/o Research, submit a letter to the IRB (consult with
IRB first);
-Concurrence from IRB Chair (not approval) is required;
-Prior FDA approval is required.
July 21, 2005
Page 15
Emergency Research
with an
Investigational Drug or Device
July 21, 2005
Page 16
Belmont Report, 1979
Articulates 3 Basic Ethical Principles:
Respect For Persons – Autonomy of the Individual
Beneficence – Risk Minimization
Justice – Burdens and Benefits of Research are Equitably Distributed
July 21, 2005
Page 17
Emergency Research with an Investigational Drug or Device
Exception from informed consent requirements for emergency
research (21 CFR 50.24, October 2, 1996):
-Regulations require many additional considerations during IRB review
-See Handout
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.24
July 21, 2005
Page 18
Emergency Research with an Investigational Drug or Device
Community Consultation
-Required under 21 CFR 50.24
-discussions with, and soliciting opinions from the community/ies in which the
study will take place and from which the study subjects will be drawn.
-may not always be the same; when they are not the same, both communities
should be consulted.
-an IRB member or representative should attend these discussions so that they
have first-hand knowledge of community reaction.
July 21, 2005
Page 19
Emergency Research with an Investigational Drug or Device
Community Consultation
FDA Guidance:
http://www.fda.gov/ora/compliance_ref/bimo/err_guide.htm#COMMUNITY
July 21, 2005
Page 20
Emergency Research with an Investigational Drug or Device
Community Consultation
Samples of community consultation done by Mayo Clinic:
http://www.fda.gov/ohrms/dockets/dailys/04/aug04/083004/95s-0158sup0028-04-Mayo-Clinic-Rochester-NM-vol28.pdf
July 21, 2005
Page 21