GUIDANCE FOR TREATMENT IND/IDE AND OTHER EXPANDED ACCESS TO INVESTIGATIONAL DRUGS AND DEVICES 

IRB approval is required before a patient can be treated with a drug, biologic, or device under a treatment IND or IDE or other expanded access use approved by FDA. 

The FDA sometimes allows the use of investigational drugs, biologics, and devices for treatment of serious or life-threatening conditions either for a single subject or for a group of subjects when no satisfactory alternative treatment exists, to treat life-threatening and debilitating illnesses. The mechanisms under which FDA allows expanded access provide patients with promising therapeutic agents without compromising the protection afforded to human subjects or the thoroughness and scientific integrity of product development and marketing approval.  These uses are approved for non emergency treatment situations outside of a clinical trial.

For these non-emergency uses of an unapproved drug or device the treating physician (or Investigator) should submit to the IRB information on all applicable elements contained in the Treatment IND/IDE form. Prior approval from the sponsor and FDA or pending approval for the proposed use for a Treatment IND, Treatment IDE, Compassionate Use IDE, Humanitarian Use Device (HUD), or other FDA approved expanded access use is required before submitting to the IRB.

Once an application is filed with the FDA, regulations state that the treatment use may begin 30 days after the application to FDA, or sooner if FDA grants written permission.  FDA may approve the proposed use as submitted or require modifications.  The FDA division with oversight responsibility for the drug or device can provide situation specific guidance regarding what information should be submitted in support of the proposed drug or device use.

Treatment Use and Other Types of Expanded Access Uses

Under FDA regulations several different options exist that allow physicians to access investigational drugs and devices in the treatment of patients. Each option has specific criteria that must be met.
                                           

Treatment IND

A Treatment IND is used when a patient does not meet the eligibility requirements of any other clinical trial and enough information has been collected to show that the drug or biologic may be effective and does not have unreasonable risks.

The treatment IND [21 CFR 312.34 and 312.35] is a mechanism for providing eligible subjects with investigational drugs for the treatment of serious and life-threatening illnesses for which there are no satisfactory alternative treatments. Treatment IND was once referred to as compassionate use. You may still hear this phrase used but it means Treatment IND. 

The FDA requires the following elements to issue a Treatment IND:

• The drug is intended to treat a serious or immediately life-threatening disease;
• There is no comparable or satisfactory alternative drug or other therapy available to treat that stage of the disease in the intended patient population;
• The drug is under investigation in a controlled clinical trial under an IND in effect for the trial, or all clinical trials have been completed; and
• The sponsor of the controlled clinical trial is actively pursuing marketing approval of the investigational drug with due diligence.

FDA regulations (21 CFR 312.34 and 312.35) address the treatment use of an investigational drug (not approved for marketing, but under clinical investigation for a serious or immediately life-threatening disease condition) in patients for whom no comparable or satisfactory alternative drug or other therapy is available. Use of the investigational drug for this purpose must meet all applicable FDA requirements.

Treatment IND studies require prospective IRB review and informed consent. A sponsor may apply for a waiver of local IRB review under a treatment IND if it can be shown to be in the best interest of the subjects, and if a satisfactory alternate mechanism for assuring the protection of human subjects is available, e.g., review by a central IRB. Such a waiver does not apply to the informed consent requirement. An IRB may still opt to review a study even if FDA has granted a waiver. 

NYU requires IRB review before a treatment IND is used, even in cases where FDA has granted a waiver.

Treatment use of an investigational drug is conditioned on the sponsor and investigators complying with the safeguards of the IND process, including the regulations governing informed consent (21 CFR part 50) and institutional review boards (21 CFR part 56) and the applicable provisions of part 312, including distribution of the drug through qualified experts, maintenance of adequate manufacturing facilities, and submission of IND safety reports.  Because data related to safety and side effects are collected, treatment INDs also serve to expand the body of knowledge about the drug. 

An investigator interested in a treatment IND should contact the sponsor directly to request approval for the use under the sponsor’s IND.  An investigator-sponsor can contact the FDA directly.  When applying for FDA approval for a treatment IND, the investigator should also apply for IRB approval by completing the Application for Treatment IND form. 

Definitions:
Serious disease: For a drug intended to treat a serious disease, a treatment use request must provide sufficient evidence of safety and effectiveness to support such use.

Immediately life-threatening disease: For a drug intended to treat an immediately life-threatening disease, the available scientific evidence, taken as a whole, must provide a reasonable basis for concluding that the drug:

• May be effective for its intended use in its intended patient population; or
• Would not expose the patients to whom the drug is to be administered to an unreasonable and significant additional risk of illness or injury.

Immediately life-threatening disease: For a treatment IND, an "immediately life-threatening" disease means a stage of a disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment.

Treatment IDE

A Treatment IDE is used when a patient does not meet the eligibility requirements of any other clinical trial, and the device is not approved for marketing but is under a clinical investigation for a serious or immediately life threatening condition.

The purpose of FDA’s treatment use provision is to facilitate the availability of promising new devices to desperately ill patients as early in the device development process as possible, before general marketing begins, and to obtain additional data on the device's safety and effectiveness.

The FDA requires the following four conditions to consider the use of an investigational device under a Treatment IDE:

• The device is intended to treat or diagnose a serious or immediately life-threatening disease or condition;
• There is no comparable or satisfactory alternative device or other therapy available to treat or diagnose that stage of the disease or condition in the intended patient population;
• The device is under investigation in a controlled clinical trial for the same use under an approved IDE, or such clinical trials have been completed; and
• The sponsor of the investigation is actively pursuing marketing approval/clearance of the investigational device with due diligence.

A device that is not approved for marketing may be under clinical investigation for a serious or immediately life-threatening disease or condition in patients for whom no comparable or satisfactory alternative device or other therapy is available. During the course of a clinical trial or prior to final action on the marketing application, it may be necessary and appropriate to use the device in the treatment of patients not in the trial under the provisions of a treatment investigational device exemption (IDE).
In the case of a serious disease, a device ordinarily may be made available for treatment use under this section after all clinical trials have been completed.

In the case of an immediately life-threatening disease, a device may be made available for treatment use under this section prior to the completion of all clinical trials. For the purpose of this section, an "immediately life-threatening" disease means a stage of a disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment. For purposes of this section, "treatment use" of a device includes the use of a device for diagnostic purposes.

An investigator interested in a treatment IDE should contact the sponsor directly to request approval for the use under the sponsor’s IDE.  An investigator-sponsor can contact the FDA directly.  After obtaining FDA approval for a treatment IDE, the investigator should apply for IRB approval by completing the Application for Treatment IDE form.  The application should include the protocol, the informed consent document, and communication with FDA and the sponsor.

FDA requires a treatment IDE application to include, in the following order:

1. The name, address, and telephone number of the sponsor of the treatment IDE;
2. The intended use of the device, the criteria for patient selection, and a written protocol describing the treatment use;
3. An explanation of the rationale for use of the device, including, as appropriate, either a list of the available regimens that ordinarily should be tried before using the investigational device or an explanation of why the use of the investigational device is preferable to the use of available marketed treatments;
4. A description of clinical procedures, laboratory tests, or other measures that will be used to evaluate the effects of the device and to minimize risk;
5. Written procedures for monitoring the treatment use and the name and address of the monitor;
6. Instructions for use for the device and all other labeling as required under 812.5(a) and (b);
7. Information that is relevant to the safety and effectiveness of the device for the intended treatment use. Information from other IDE's may be incorporated by reference to support the treatment use;
8. A statement of the sponsor's commitment to meet all applicable responsibilities under this part and part 56 of this chapter and to ensure compliance of all participating investigators with the informed consent requirements of part 50 of this chapter;
9. An example of the agreement to be signed by all investigators participating in the treatment IDE and certification that no investigator will be added to the treatment IDE before the agreement is signed; and
10. If the device is to be sold, the price to be charged and a statement indicating that the price is based on manufacturing and handling costs only.

Compassionate Use IDE

Unlike Treatment INDs, the FDA does allow a specific category for compassionate use of an investigational device that is separate from the Treatment IDE.  The compassionate use IDE is a use intended for situations where there is a serious but not life threatening condition.

An IDE supplement submitted to the FDA for approval of a Compassionate Use IDE should contain the following 

• A description of the patient's condition and the circumstances necessitating treatment
• A discussion of why alternatives therapies are unsatisfactory and why the probable risk of using the investigational device is no greater than the probable risk from the disease or condition
• An identification of any deviations in the approved clinical protocol that may be needed in order to treat the patient; and
• The patient protection measures that will be followed. (Informed consent, concurrence of IRB chairperson, clearance from the institution, independent assessment from uninvolved physician, authorization from IDE sponsor)

Compassionate use device policy:  The compassionate use provision allows access for patients who do not meet the requirements for inclusion in the clinical investigation but for whom the treating physician believes the device may provide a benefit in treating and/or diagnosing their disease or condition. This provision is typically approved for individual patients but may be approved to treat a small group.

FDA recognizes that there are circumstances in which an investigational device is the only option available for a patient faced with a serious, albeit not life-threatening, disease or condition. In these circumstances, FDA uses its regulatory discretion in determining whether such use of an investigational device should occur.

Prior FDA approval is needed before compassionate use occurs. In order to obtain Agency approval, the sponsor should submit an IDE supplement requesting approval for a protocol deviation under section §812.35(a) in order to treat the patient.

The physician should not treat the patient identified in the supplement until FDA approves use of the device under the proposed circumstances. In reviewing this type of request, FDA will consider the above information as well as whether the preliminary evidence of safety and effectiveness justifies such use and whether such use would interfere with the conduct of a clinical trial to support marketing approval.

If the request is approved, the attending physician should devise an appropriate schedule for monitoring the patient, taking into consideration the investigational nature of the device and the specific needs of the patient. The patient should be monitored to detect any possible problems arising from the use of the device.

Following the compassionate use of the device, a follow-up report should be submitted to FDA as an IDE supplement in which summary information regarding patient outcome is presented. If any problems occurred as a result of device use, these should be discussed in the supplement and reported to the reviewing IRB as soon as possible.

The above compassionate use criteria and procedures can also be applied when a physician wishes to treat a few patients rather than an individual patient suffering from a serious disease or condition for which no alternative therapy adequately meets their medical need. In this case, the physician should request access to the investigational device through the IDE sponsor. The sponsor should submit an IDE supplement that includes the information identified above and indicates the number of patients to be treated. Such a supplement should include the protocol to be followed or identify deviations from the approved clinical protocol. As with single patient compassionate use, a monitoring schedule should be designed to meet the needs of the patients while recognizing the investigational nature of the device. Follow-up information on the use of the device should be submitted in an IDE supplement after all compassionate use patients have been treated. 

Humanitarian Use Device
A HUD is a medical device that is intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer that 4000 individuals in the United States each year.  It is exempt from the regulatory effectiveness requirements in place for other devices.  FDA considers these applications when no comparable device is available 

FDA must grant HUD status and approve a Humanitarian Device Exemption (HDE) for a device to be approved as an HUD.  This requires applications the FDA for HDE and HUD approval. This application is typically submitted by the sponsor. The FDA requires IRB review and approval before a HUD can be used.

Other FDA approved expanded access use for a drug/biologic/device: 
For situations where the FDA has approved another type of expanded access use for patients, the physician should complete the Treatment IND/IDE form with all relevant information, to include communications with FDA, the approval letter, and related information submitted that describes or supports the type of patient, use, and protections involved in the expanded access use.  The treating physician (or investigator) should submit the form for IRB review and approval of the proposed use. 

FDA may allow the use of an unapproved drugs or devices under various mechanisms for the treatment of serious or life-threatening conditions, either for a single subject or for a group of subjects, outside of current ongoing clinical trials.  For those instances where the sponsor and FDA approve expanded access to a drug or device for a patient outside of typical mechanisms, using a term other than a “treatment” use or “compassionate” use, the relevant information in the Application for Treatment IND/IDE form includes information such as the details of the proposed treatment and patient characteristics.  The application for FDA approval and the approval letter for the use should be included with the Application for Treatment IND/IDE form.

If you have any questions about an expanded access use, you can contact the IRB Office 212-263-4110.