AAOS Bulletin - August, 2005

Don’t expose yourself or your institution to unnecessary risk

Not every medical device can be used “off label”

By the AAOS Biological Implants Committee

Physicians should be aware that the prerogative to employ medical devices for uses other than those cleared or approved by the Food and Drug Administration (FDA) may, in certain instances, put both the physician and the institution at risk for liability. In most instances, a physician’s “off-label” use of a medical device is considered appropriate if, in the physician’s opinion, the device is used in the best interest of the patient. However, physicians who use medical devices that have been approved by the FDA under the Humanitarian Device Exemption (HDE) regulatory pathway (21 CFR Part 814 Subpart H) must consider additional requirements and recommendations before using such devices in an off-label manner.

HDE-approved device characteristics

The FDA grants HDE marketing approval to a Humanitarian Use Device (HUD) when that device meets specific criteria:

• The device is intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect or are manifest in fewer than 4,000 individuals in the United States annually.

• There is no other comparable device, other than another humanitarian use device authorized under HDE (or an investigational regulatory pathway), available to treat or diagnose the disease or condition.

The FDA does not consider HUDs as investigational, nor does the FDA require patient informed consent for their use. However, an institution may superimpose additional requirements for HUDs. Accordingly, physicians should be alert to potential additional regulations governing the use of HUDs

Physicians should also be aware that the FDA reviews manufacturer applications for HDE status for reasonable assurances of safety and probable benefit, but not for effectiveness. The manufacturer of the HUD does not need to provide the FDA with data demonstrating the device’s efficacy. All HDE product labeling must include the following statement: “Humanitarian Device. Authorized by Federal law for use in the [specify treatment or diagnosis] of [specify disease or condition]. The effectiveness of this device for this use has not been demonstrated.”

Under the HDE pathway, the FDA authorizes marketing of the HUD specifically for the indication(s) noted on the HDE application. If the manufacturer seeks a new indication for the use of an HDE-authorized device, it must obtain a separate HUD designation for the new indication, as well as submit a new HDE application for that desired indication.

The need for IRB approval

Physicians who elect to use HDE-approved devices must secure Institutional Review Board (IRB) approval before administering or implanting the device into a patient. The HUD may be administered to patients only if such use has been approved by the IRB located at the facility or by a similarly constituted IRB that has agreed to oversee such use. The only exception is in emergency situations which, in the physician’s judgment, may result in serious harm or death to the patient without intervention. In such cases, the physician must notify the IRB within five days of the use of the humanitarian device.

The IRB is responsible for providing initial and continuing review of the device. It can approve the use of an HUD only for the FDA-authorized indications of the device. As a result, the use of the HUD may be restricted, by the authority of the IRB, to the indications for which it is authorized.

A physician who uses an HDE-approved device for any purpose other than emergency use, compassionate use, or the IRB-approved indication is acting outside the scope of his or her IRB approval. This may lead to institutional as well as individual liability.

Physician-directed or “off-label” uses

The use of a device for other than its FDA-approved indication is an off-label use. Generally, physicians may use a device off-label if they are not conducting clinical research and if they believe, in their best medical judgment, that its use is appropriate for a particular patient. The FDA does not regulate the practice of medicine. Physician-directed or off-label use of medical devices is simply an additional treatment or diagnostic tool within the physician’s toolbox, and does not alone reflect pejoratively on the physician’s medical judgment, practice management or quality of care delivered to the patient.

However, provisions in the HDE regulatory pathway include both a requirement for IRB approval and additional strong recommendations for physicians who intend to employ such devices for any off-label uses. Because IRB review and approval is required before using an HDE-approved device within the scope of its approved labeling, an HDE-approved device should not be used outside the scope of its approved labeling. Remember, HDE-approved devices have not demonstrated effectiveness, but only safety and probable benefit.

Appropriate off-label uses

In an emergency situation, an HDE-approved device may be used off-label to save the life or protect the physical well-being of a patient. The physician and the HDE holder (manufacturer) should follow FDA emergency use procedures governing the use of unapproved devices. Prior to use, the physician should obtain concurrence from the chair of the IRB, informed consent from the patient or his/her legal representative, and an independent assessment by an uninvolved physician, in addition to authorization from the HDE holder. Afterward, the physician should submit a follow-up report to the HDE holder on the patient’s condition and any patient-protection measures taken. The HDE holder would then submit this as a report to the FDA.

An HDE-approved device may also be used off-label for compassionate use. In this case as well, the physician should ensure that patient-protection measures are addressed before the device is used on a compassionate basis. In addition, prior FDA approval for each compassionate use of an HUD is recommended. A physician who wishes to utilize an HDE-approved device for compassionate use should provide the HDE holder with the following:

• A description of the patient’s condition

• The circumstances necessitating treatment with the device

• A discussion of why alternative therapies are unsatisfactory

• Information addressing patient protection measures

The HDE holder would then submit the report to the FDA for an expeditious review.

Furthermore, compassionate use also requires the physician to devise an appropriate schedule for monitoring the patient, taking into consideration the limited information available regarding the potential benefits of the device and the specific needs of the patient.

Conclusion

The physician’s use of a medical device for other than its FDA-cleared indication(s) is generally acceptable if the physician believes that the use is appropriate for a particular patient. However, the physician who uses HDE-approved devices must realize that IRB approval is mandatory and may restrict the use of the HDE-approved device to its FDA-authorized indication. Any physician who uses HDE-approved devices outside the authority of the IRB approval and without the patient-protection measures identified above, places him- or herself, along with the institution, at potential risk. Physicians should also be aware that, in reviewing an HDE application, the FDA evaluates only the reasonable safety and probable benefit—not the efficacy—of the device.

The FDA Safe Medical Devices Act of 1990 requires hospitals and other user facilities to report deaths and serious injuries associated with the use of medical devices. The Academy requests that fellows follow the procedures established by your facility for such mandatory reporting when an adverse event occurs with the use of any medical device.

The Biological Implants Committee monitors scientific, regulatory and technical advancements in biologic and combination products related to orthopaedic surgery. Katherine Sale, staff liaison, can be reached at sale@aaos.org. The committee wishes to thank Elisa D. Harvey, DVM, PhD, of the FDA for assistance in preparing this article.


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