Section XVI:

FDA - Regulated Products

WPP #: XVI-5

Title 5:

Non-Research (Treatment Use, Single Patient Use, Parallel Track Program)

Effective Date:

6-21-06

Revision History:

06-07-04

Objective

To describe the non-research uses of investigational products where IRB oversight is required, including emergency use, treatment use, single patient treatment use, and parallel track programs.

Description

IRB reviews the non-research use of investigational drugs/devices the use of investigational drugs/devices if the physician provides evidence that a treatment IND/IDE has been obtained or plans for a single patient use (as described below in Section B). In all cases, treatment use of an investigational drug/device requires prospective IRB approval as well as subject informed consent.

  1. Emergency Use:

    See the following VCU IRB WPPs regarding Non-Research Emergency Use:
    VCU IRB WPP#: XVI-3 (Emergency Use of Unapproved Medical Devices)
    VCU IRB WPP#: XVI-4 (Emergency Use of Investigational Drugs or Biologics)

  2. Single Patient Use
    1. Definition: In non-emergency situations, single patient use allows a physician to obtain access to an investigational drug, device, or biologic upon receiving approval from the IRB. This approval is granted for the treatment of a single patient.
    2. Procedure: When an investigator desires to obtain single patient use approval, the investigator submits an application and the "activity under review" is assigned a VCU IRB identification number and sent through the new application procedure. The treatment use may occur only after IRB approval is obtained. Subsequent treatment use requires FDA approval for a treatment IND/IDE [21 CFR 312.35].

      The following must be submitted to the IRB for Single Patient Use:

      1. VCU IRB Application with all required attachments
      2. Title of the protocol must clearly indicate SINGLE PATIENT USE request
      3. Complete description of the use (non-research protocol)
      4. Drug/Biologic/Device brochures and labeling
      5. Reference to any applicable IND/IDE
      6. Previous safety data
  3. Treatment Use:
    1. Definition: A treatment IND is a treatment protocol that is added to an existing investigational new drug application (IND), which allows physicians to treat qualifying patients according to the protocol, and which provides additional data on the drug's safety and effectiveness. Treatment INDs are available for patients with life-threatening or other serious diseases for which no satisfactory alternative drug or other therapy exists [21 CFR 312.34].
    2. Procedure: The FDA permits Treatment INDs only for drugs that show some promise of therapeutic benefit. Two standards exist:
      1. For serious diseases, applications for Treatment INDs must show sufficient evidence of safety and effectiveness to support the use. Ordinarily, this standard means that a drug may be made available for treatment use either during Phase 3 investigations or after all clinical trials have been completed.
      2. For immediately life-threatening diseases, the evidence, taken as a whole, must show (i.e., there must be sufficient data reasonably to conclude) that the drug may be effective for its intended use in its intended patient population and would not expose the patients to whom the drug is to be administered to an unreasonable and significant additional risk of illness or injury. Under this standard, investigational drugs for treating immediately life-threatening diseases may be made available for treatment use earlier than Phase 3, but ordinarily not earlier than Phase 2 [21 CFR 312.34(a), 312.34(b)(2), and 312.34(b)(3)].
    3. Treatment INDs must be reviewed by the VCU IRB prior to their submission to the FDA and must comply with the regulations governing informed consent (21 CFR Part 50) and IRBs (21 CFR Part 56) [21 CFR 312.34(c)]. While the FDA will consider waiving local IRB review for Treatment INDs, if waiver is in the best interests of the subjects and adequate alternative mechanisms for human subject protection are provided (e.g., to avoid duplication when a national review body has already reviewed the Treatment IND), VCU DOES REQUIRE LOCAL IRB REVIEW.

      The following must be submitted to the IRB for Treatment Use:

      • VCU IRB Application with all required attachments
      • Title of the protocol must clearly indicate TREATMENT USE request
      • Complete description of the use (non-research protocol)
      • Drug/Biologic/Device brochures and labeling
      • Reference to any applicable IND/IDE
      • Previous safety data
  4. Parallel Track Program:
    1. Definition: The Parallel Track mechanism makes available promising investigational agents as quickly as possible to persons with AIDS and other HIV-related diseases while generating data on the safety and effectiveness of the drug [Federal Register 57 (April 15, 1992): 13250-13259]. Under the FDA policy, persons with AIDS and HIV-related diseases who are not able to take standard therapy or for whom standard therapy is no longer effective, and who are not able to participate in ongoing controlled clinical trials would have access to promising investigational drugs.

    2. Procedure: Applications for consideration of experimental therapies for Parallel Track expanded availability must be submitted to the FDA as amendments to existing INDs.

      Parallel Track protocols are accomplished under the Treatment IND mechanism, which is described above, and should be thought of as a subset of the Treatment IND. They are distinguished from Treatment INDs by the amount of evidence of effectiveness required. Treatment INDs may be granted after sufficient data have been collected to show that the drug "may be effective" and does not have unreasonable risks, but before marketing approval has been granted. According to the FDA, Parallel Track protocols "might be approved for promising investigational drugs when the evidence for effectiveness is less than that generally required for a Treatment IND" [Federal Register 57 (April 15, 1992): 13256]. In other words, Treatment INDs have represented an attempt to move drugs from late Phase 2 into Phase 3, and Parallel Track represents an attempt to move drugs from late Phase 1 into Phase 2, both with the intended purpose of making promising new agents available to persons with life-threatening diseases who cannot participate in controlled clinical trials and for whom there are no satisfactory alternative therapies. In addition, the Parallel Track mechanism is available only for AIDS and other HIV-related diseases, while the Treatment IND is available for a number of serious or life-threatening conditions.

      While both DHHS and the FDA may allow waiver of local IRB review for certain Parallel Track programs, the VCU REQUIRES VCU IRB REVIEW.

Responsibility

It is the responsibility of the medical professional to determine the appropriate type of non-research treatment and meet all regulatory requirements prior to submission to the IRB.

References

FDA Information Sheet: "Treatment Use of Investigational Drugs"
21 CFR 56.104