Single Patient IND

Question 1:

Our IRB program has a few questions regarding the IRB responsibilities for the review of a single patient IND, in particular, one that involves an oncology drug. I would appreciate it if I could get direction on some of the questions below.

1) Sponsor provided Emergency Use Program

Physician received approval from the FDA for a single patient IND

IRB was directed by FDA Authorizing Official of Single Patient IND to consider this as a compassionate use single-patient IND, but there are no regulations specifically for compassionate use

Involves the use of an investigational drug

Sponsor documents this as Emergency Use

2) What are the IRB responsibilities for review of this effort?

Physician states that there are no further effective options for patient; patient is in a life-threatening situation in which there is no standard acceptable treatment; patient involvement in investigational drug trials have had no effect

Physician has received drug from Sponsor

IRB has acknowledged notification of investigational drug use by physician

Physician does not want to begin treatment until receipt of IRB “approval” (as noted on FDA Approval of single patient IND)

IRB Membership comments/concerns:

a) physician members and a community member who is a cancer survivor noted that this situation should be viewed as `emergency use' with respect to the patient's illness and time is of the essence; treatment should not be delayed for IRB “approval

b) What are the IRB responsibilities- the members stated that they would never “disapprove” its use for the case reviewed; must respect the patient

c) IRB Chair asked: Is there legislation that allows the patient to request these investigational drugs? If so, the IRB would not “disapprove” the use

d) IRB Chair noted that the IRB has no authority to make any changes to the Sponsor provided consent form since it is part of a program

e) IRB Chair questioned what is within the purview of the IRB in terms of methods in approving the effort- can the IRB vote for “approval of use” via email? By phone prior to the Full IRB meeting?

f) Is it true that treatment cannot begin prior to Full IRB approval?

3) Subsequent requests- can they be expedited if it is the same drug?

4) Because an IND is involved, does this constitute research? Or is this treatment?

Answer 1:

Part of the difficulty in this instance is the lack of detailed discussion of the specific circumstances in either FDA regulation or guidance. The IND regulation - 21 CFR Part 312 - does allow for emergency use (312.36) of an investigational product as well as treatment use (312.83). Both possibilities involve use of the drug in individuals who do not meet the inclusion/exclusion criteria of an existing IND study but whose condition is deemed such that this would be his/her best treatment choice. Since the IND was approved for a single individual, it does not presently meet the treatment IND regulation specifics, though an expansion of this sort has been proposed as part of a draft regulatory change proposed in December 2206 ( I believe you will find the discussion found there applicable to your present circumstances, though it is only a proposed regulatory change and not present FDA regulation or guidance.

I will attempt to address some of your concerns. Since the Center for Drug Evaluation and Research (CDER) has granted an IND for use in this one individual, you can accept that as FDA approval of its use in this circumstance. The physician is requesting IRB approval as all uses of investigational products require that proper human subject protections be followed, which for FDA-regulated products means IRB approval and use of appropriate informed consent. The IRB is the community's body delegated to protect the rights, safety, and welfare of those treated at the institutions covered by the IRB. I do not agree with your statement that your IRB could not appropriately make changes to the informed consent document. If you consider changes a necessary condition for your approval, than request of such changes is appropriate - that is indeed within your purview.

Since it is an oncology drug, it would indeed seem treatment should be started as soon as possible, if the IRB considers it an approvable use. While it should most likely be discussed by at least a quorum of the IRB membership, teleconferencing in members is possible, as long as each member participating receives all necessary information in advance and all are therefore capable of fully discussing the issues before voting. In true emergency use situations (individual requires immediate use), concurrence by an IRB chair or his/her delegate can be considered sufficient. However, this circumstance does appear to fall between an emergency use and treatment use and not truly fit either. Therefore, if full review can be obtained ASAP, that would be preferable.

INDs approved for a single individual are intended to be treated in the same way as emergency use as far as further similar use. That is, no further similar uses can occur unless and until the sponsor develops a treatment IND that would cover multiple subjects and that IND receives CDER approval. Since it is an investigational drug, its use under this single individual IND is considered research and the attending physician is expected to follow the progress of the patient and maintain appropriate records. That information will be used as part of the safety evaluation for the product, if and when a marketing application is submitted to FDA.

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