1. Less Frequently Used Types of INDs IRB Education for june 2013

2. Review from February 2013 What is an Investigational New Drug Application (an “IND”)? What are the differences between an emergency and a non-emergency use? How is the IRB involved?

3. What qualifies as an “emergency” for “emergency IND for single use” purposes? • To be considered “emergency use” that is exempt from prospective IRB approval, look to the FDA’s definition of the term. • “Emergency use” has two essential components: • a life-threatening situation in which no standard acceptable treatment is available and • insufficient time to convene a quorum for full-board IRB approval.

4. IND: The Informed Consent Component The “informed consent statement” for the IND is a statement from the physician that informed consent and approval of the use by an appropriate IRB will be obtained prior to initiating treatment. The patient must understand the investigational nature of the drug, and typically, the manufacturer will supply the consent form. However, the IRB is NOT involved in the review or approval of the consent form if the situation meets the criteria for “emergency use.” Instead, in the case of an emergency IND for use with only one patient, treatment may begin WITHOUT prior IRB approval as long as the IRB is notified of the emergency treatment within five working days of the emergency use of the test drug. 21 CFR 56; 21 CFR 50; and 21 CFR 312

5. Waiver of Consent • Consent must be obtained, UNLESS the investigator and another physician believe and will certify, in writing, all of the following: • The human subject is confronted by a life-threatening situation that necessitates the use of the test article (an investigational drug, device, or biologic). • Informed consent cannot be obtained because of an inability to communicate with, or to obtain legally-effective consent from, the subject or the subject’s legally-authorized representative (“an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research”). • Time is not sufficient to obtain consent. • No alternative method of approved or generally-recognized therapy is available that will provide an equal or greater likelihood of saving the subject's life.

6. IRB Notification Notification of the IRB v. IRB Approval 5-day time frame Sponsor-Investigator’s letter to the IRB

7. Planned Emergency Research • What are the elements of “emergency research?” • The research has the prospect of providing a direct benefit to the patient. • The research must involve an investigational article. • The article, in order to be effective, must be administered before informed consent from the subject (or from the subject’s legally-authorized representative) can be obtained. • There is no reasonable way to identify, prospectively, individuals likely to become eligible for participation in the research.

8. Concerns Regarding Emergency Research What are the concerns surrounding emergency research? How does the FDA address these concerns? 21 CFR 50.24

9. Waiver of Consent with Emergency Research Elements of emergency research are fulfilled Potential benefit shown for research subjects Risk analysis completed Need for waiver established Investigator shows commitment to contacting LARs, as applicable

10. Waiver of Consent • IRB has reviewed and approved all consent procedures and documents • Additional protections include the following (at a minimum): • Consultation with community representatives • Public disclosure • Regarding the risks and possible benefits of the study • Regarding the results of the study upon completion

11. Additional Protections (Continued) Establish an independent data monitoring committee Investigator shows commitment to contacting family members, as applicable IRB is responsible for procedures related to informing the subject, subject’s LAR, or subject’s family member

12. Conclusion Other points to consider IRB Education, Part 2 for June 2013