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

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

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

Emergency Use of an Investigational Drug or Device July 21, 2005

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

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

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

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

Compassionate Use with an Investigational Drug or Device July 21, 2005

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

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

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

Compassionate Use of an Investigational Device 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

Compassionate Use of an Investigational Device 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

Emergency Research with an Investigational Drug or Device July 21, 2005

Articulates 3 Basic Ethical Principles: 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

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

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

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

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-0158-sup0028-04-Mayo-Clinic-Rochester-NM-vol28.pdf July 21, 2005