FDA Clarifies its Expectations from IRB Review of Compassionate Use
(Thursday, September 14, 2023) Emergency use or compassionate use protocols rely heavily on IRB review of such use of an investigational product. Individual patients in life-threatening conditions can be treated without prior approval by the FDA or an IRB with the expectation that the physician using an investigational treatment on his/her patient would inform the FDA and a relevant IRB within 5 days of treating the patient. To help IRBs understand their responsibilities in such situations, the US FDA just released a new Guidance Document defining its expectations for the IRB review. Expanded use of an investigational product, also known as compassionate use or emergency use, requires expedited reviews both at the FDA and the IRBs. If there is time, physicians are expected to file an emergency use IND with the FDA before treating the patient. The emergency use IND for individual patients involves submitting a short form, FDA 3926, along with a cover letter, to the FDA by the treating physician. FDA usually responds within 1-2 days of receipt of FDA 3926. In parallel with the FDA review, the physician is expected to also obtain approval from an IRB, if possible, prior to treatment, or within 5 days of the treatment, in case the patient’s life is at risk and it is not possible to delay the treatment for the approval. The IRBs are expected to review such requests expeditiously. The FDA’s new guidance document clarifies the process for such expedited IRB review. A single IRB member, such as an IRB chairperson or a designated member, should review an individual patient expanded access submission. The physician requesting such approval is responsible for providing comprehensive information about the patient and the treatment regimen with the investigational treatment such that the IRB reviewer can make a reasonable assessment of the potential risks and benefits to the patient being treated. This includes thorough patient history, diagnosis, prior therapy response, and the reason the investigational treatment is being proposed. Relevant clinical characteristics, such as comorbid conditions and concomitant medications, should also be provided to assess potential risks associated with the drug. For the treatment, the physician is required to provide the proposed dose and dosing regimen, planned monitoring for adverse events, response to treatment, changes in clinical status, and the criteria for discontinuation of treatment or dose modifications for adverse events. Further, the IRB should assess the qualifications of the treating physician for his/her ability to provide appropriate patient care. Expanded access also requires obtaining adequate informed consent signed by the patient or their legal representative or parent for the pediatric patients, disclosing the experimental nature of the treatment, just like would be needed for a clinical trial. There is no need for a full-fledged protocol for individual patient expanded access treatments. The recommendations in the new Guidance Document do not apply to expanded access programs where more than one patient is treated. In those cases, prior approvals from both the FDA and the IRBs are required. These IRB expectations in the case of expanded access protocols have been well established over the last two decades. The new guidance document, hence, does not present any surprises. However, it does present another evidence of the FDA’s strong support for the expanded access program. To the cynical, it may seem like another snub of the Right-To-Try use which is another way investigational drugs can be used in patients in similar circumstances, albeit without FDA or IRB approvals. The FDA Guidance Document does not discuss Right-To-Try situations. Perhaps, it was not in the scope of this guidance, or maybe there are other motives. AUTHOR
Dr. Mukesh Kumar Founder & CEO, FDAMap Email: [email protected] Linkedin: Mukesh Kumar, PhD, RAC Instagram: mukeshkumarrac Twitter: @FDA_MAP Youtube: MukeshKumarFDAMap |
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