Human Research Protection Program (HRPP)

Most administration/use of unapproved devices, drugs or biologics is part of a systematic clinical trial. All clinical investigations, including pilot studies, require prior IRB review and approval. Almost all clinical studies are conducted under an Investigational Device Exemption (IDE) or an Investigational New Drug (IND) exemption obtained from the FDA.

Use of an investigational drug, biological product, or medical device generally requires either an IND (for unapproved drugs and biologics) or an IDE (for unapproved devices).

However, the FDA's “emergency use” exemption allows the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and in which there is not sufficient time to obtain IRB approval.

A physician who treats a patient under emergency use provisions must justify the treatment according to strict criteria, consult with the IRB, and fulfill specific follow-up/reporting responsibilities in a timely manner, as described in detail below.

Note: Emergency use is emergency clinical care and does not meet the DHHS definition of research. IRB agreement that a particular case meets FDA criteria for emergency use applies to the treatment of one patient only and is not the same as IRB approval to conduct a research study.

Expanded access, sometimes called "compassionate use," is the use outside of a clinical trial of an investigational medical product. A patient may be able to receive the product (when appropriate) through expanded access when enrollment in a clinical trial is not possible, e.g., a patient is not eligible for any ongoing clinical trials, or there are no ongoing clinical trials. 

Such use of an investigational drug, biologic or device falls into one of the following expanded access treatment mechanisms. Prior IRB review and approval is required, even if only one patient is to be treated under the following mechanisms. In most circumstances, prior approval by the FDA is also required.

Expanded Access Treatment Mechanisms: 

Treatment INDs or Individual Patient Access to Investigational Drugs/Devices for Serious Diseases: These mechanisms are primarily intended to give seriously ill patients access to experimental drugs or devices where no comparable or satisfactory alternative treatment is available. Although the test article sponsor is expected to continue conventional clinical trials and pursue marketing approvals with due diligence, expanded access studies involve systematic use of experimental treatments, and, with very rare exceptions, require the same review and approval as research, including both IRB approval and FDA approval in the form of an IDE (medical device) or an IND (drug/biologic).

Open Protocols (Parallel Track, Open Label Protocol, Open Label IND) or Continued Access IDEs: These uncontrolled studies are typically used when controlled trials have ended and treatment is continued so the subjects may continue to receive the benefits of the test article until marketing approval is obtained. Informed consent and prior IRB approval are required.

To allow treatment of a single patient who does not meet the entry criteria of an IRB-approved protocol, the PI should submit a written request to IRB for a one-time, one-patient enrollment exception. Such a request, which should be rare, must be justified in terms of serving the best interests of the patient.

See the enrollment exception info on Modification page for info on how to submit this request. Note: IRB approval is required before the exception can be made.

Planned research designed to evaluate emergency care treatments is not “emergency use.” As with all other clinical research, prospective IRB review and approval are required before a clinical study in emergency medicine can begin. See the Research in Emergency Settings page for details, including info on the emergency medical research waiver of informed consent.

Emergency use provisions apply to investigational drugs, biologics and devices. The innovative use of a marketed drug or device (sometimes called “off-label” use) for individual patient treatment rather than for research purposes does not require IRB review.

Important Note: Treating a series of patients in a novel or innovative manner and analyzing the results for publication is research requiring prior IRB review. Review the "Innovative Procedures, Treatment or Instructional Methods" section of the Quick Guide: Activities Requiring IRB Review for more info.

An HDE is a special approval given by the FDA that allows marketing a device that is designed to treat or diagnose a condition that affects no more than 8000 individuals per year. An HDE is given even though the efficacy of the device has not been tested or proven, because it is not financially feasible to do the usual clinical testing when so few individuals are affected. The FDA requires IRB approval prior to use of a Humanitarian Use Device (HUD), even though the use is not considered research.

The IRB requires a standard application, use of a consent form similar to research consent and annual review. The initial review for this application must be done by the full committee; however, the annual continuing reviews can be done through expedited procedures. Call the IRB office for additional guidance. UCSF guidelines are under development.

Physicians are often enthusiastic about the possible benefits of an investigational drug or device. However, the lack of FDA approval usually means the safety and efficacy have not been scientifically proven. The possible, but unproven, benefits of the experimental treatment must be weighed against its risks and against the possible benefits of available alternatives.

Although the FDA tracks test article emergency use, clinical data obtained from the use contributes little to the overall statistical evaluation of the treatment. The potential benefit is only to a single patient; there is little potential societal benefit from increasing scientific knowledge.

The physician should carefully consider that the standard is higher for emergency use informed consent than for routine clinical care. Given the life-threatening or potentially disabling condition of the patient, it is critical that the consent form clearly states that there is no guarantee of benefit from the emergency use procedure. Guidance on obtaining informed consent is provided below.

1. Read the FDA's Emergency Use of an Investigational Drug or Biologic - Information Sheet

2. Contact the FDA to obtain an emergency IND (FDA contact numbers are listed on the above Information Sheet)

3. Once the emergency IND is obtained from the FDA, email the following to [email protected] with "Emergency Use Request" in the Subject line:

a. Request for Emergency Use Form

b. FDA approval correspondence or eIND if FDA approval was given over the phone

​Please note: If the FDA has issued an emergency IND and states that you may proceed, you may do so without IRB concurrence if waiting could jeopardize the patient’s well-being. Per the regulations, Emergency Use of an investigational drug or biologic is exempt from prospective IRB approval, provided the FDA has approved the emergency use request.

Also note: Emergency Use is not the same as a non-emergency Single Patient IND. The physician should discuss with the FDA if there are questions about whether a case is emergency use or non-emergency.

Per FDA, the following conditions must apply for Emergency Use:

Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life threatening or to immediately result in death. Rather, the patients must be in a life-threatening situation requiring intervention before obtaining FDA approval.

Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand or foot, loss of hearing, paralysis or stroke.

Before the emergency use, every effort should be made to obtain informed consent signed by the patient or the patient’s surrogate (legally authorized representative). If written informed consent is not possible, there are special provisions for an informed consent waiver.

Whether the physician writes the consent or uses a template consent from another source (e.g. the sponsor/manufacturer of the test article), the emergency use consent should contain the elements of informed consent found in the UCSF template, but need not follow the UCSF format and wording. It must be stated clearly that:

• the patient is not part of a UCSF-approved research study,
• the treatment is experimental and not approved by the FDA, and
• there is no guarantee of benefit.

Because the FDA exempts emergency use from requirements for IRB review, prior IRB approval of the consent form is not needed. A signed copy of the informed consent must be included in the Emergency Use Post-use Report Form. 

Waiver of Consent:

If prior consent is not possible, federal regulations [21 CFR 50.23] allow a waiver under the following conditions:

• If at all possible, before the emergency use the treating physician and a physician not involved in clinical investigation of the test article certify in writing that:

1. The patient is confronted with a life-threatening situation.
2. The physician cannot communicate with the patient.
3. Time is not sufficient to obtain consent from the patient’s surrogate (legally authorized representative).
4. No alternative method of approved or generally recognized therapy is available that provides equal or greater likelihood of saving the patient’s life.

• If immediate use of the test article is needed to preserve the patient’s life, and there is not sufficient time to secure an independent physician’s determination that the four conditions described above apply, the treating physician must have the written determination reviewed and signed by an independent physician within five working days after the emergency use of the test article.
• Include a copy of the written determination with the post-use written report.

The FDA requires the treating physician to document the emergency use in writing and submit the report to the IRB within five (5) working days of emergency use initiation. The physician must use the Emergency Use Post-use Report Form.