Considerations When Disseminating Off-Label Information

How is the dissemination of information regarding an unapproved indication for an approved drug or medical device like speeding on the highway? You might not get caught, but it can be dangerous and it might land you in court.

Most pharmaceutical and medical device companies promote their products for unapproved ' or off-label ' uses. The term “off-label” as used in this article refers to a situation in which the Food and Drug Administration (FDA) has approved or cleared the sale of a product for a particular indication, but a company markets it for a different use. Companies can make millions of dollars on off-label sales and, in some cases, the sales associated with off-label use are more profitable than sales associated with the authorized indication. Off-label promotion is a business reality. However, gains from off-label promotions can be quickly offset by costs associated with product liability litigation and the loss of good will within the medical and consumer communities.

Off-Label Use

Unless specific statutory and regulatory conditions described in the Food and Drug Administration Modernization Act and the FDA's implementing regulations are met (which are not discussed here), off-label dissemination is not legal. Many, if not most, companies that distribute materials to healthcare professionals about a product's off-label use do not strictly adhere to the law. After weighing projected increases in sales, along with competitive pressures, companies frequently take the risk associated with off-label promotion.

Companies, and the FDA, are familiar with several court decisions that have stymied the FDA's enforcement approach in the promotional area. Companies realize that the court decisions, as well as the FDA's limited resources when compared with the thousands of off-label promotional materials disseminated by or on behalf of the drug or device industry, mean that the FDA simply cannot, and will not, take regulatory action against all off-label promotion. Due to what is perceived by some as a hesitant FDA, many companies feel empowered to distribute aggressively off-label information with a sense of “FDA, catch me if you can.” However, such a strategy is short sighted and can result in disastrous product liability lawsuits that may result in financial and public relations nightmares.

By definition, “off-label” means that the promoted indication is not on the product's approved or cleared label. It does not necessarily mean that the use is unsafe or ineffective; the company may (and should) have substantiating data that the use is safe and effective. Because the off-label use is not “FDA-approved,” a company should recognize that, by disseminating off-label information, it increases its exposure to product liability claims.

In many cases, a company distributes off-label information to healthcare professionals. If, based on the dissemination, a doctor uses the product for the promoted off-label indication and an injury results, the company may be subject to a product liability claim. Even if the company can successfully defend itself using the learned intermediary doctrine or other legal principles, the company, with perceived deep pockets and insurance coverage, will no doubt find itself listed as a defendant in a product liability lawsuit.

Off-Label Litigation

An example of off-label promotion resulting in numerous product liability lawsuits involved bone screw implantable medical devices. The cases arose from injuries allegedly caused by orthopedic bone screw devices. Although the FDA had not authorized the devices for use in pedicle fixation surgery, manufacturers of the device allegedly actively promoted this use during seminars and other events. Approximately 5000 individuals filed suit against the manufacturers claiming injury from the devices. In Re Orthopedic Bone Screw Products Liability Litigation, 193 F.3d 781 (3d Cir. 1999). Although individuals cannot bring private causes of action against a company for violations of the Federal Food, Drug, and Cosmetic Act (FDC Act), the plaintiffs used the statute as a basis to argue that the manufacturers acted negligently through their promotion of unapproved uses. The manufacturers responded that the doctors used the devices in the course of their practice of medicine. The cases resulted in the manufacturers having to defend numerous claims in numerous states, each with its own set of laws.

Recommendations

The following are some recommendations for manufacturers to minimize product liability and regulatory risks.

1) Just Say No

Do not engage in any off-label promotion. Stick to the FDA-approved or cleared product labeling and file applications or supplements for new indications.

2) If You Do It …

• Comply with the FDA's requirements for off-label dissemination.
• Establish procedures that control the dissemination of off-label information before distribution (eg, an internal review checklist that requires sign off by appropriate personnel) and a team to review all promotional materials, regardless of the intended audience or the form of the promotion.

The team should include individuals from medical affairs, marketing, regulatory affairs, quality assurance, in-house counsel and, if appropriate, outside regulatory counsel.

The purpose of this review is to verify the accuracy of the information and claims about the product and to ensure that there are no implied or ambiguous representations.

Particular attention should be given to whether warnings or cautionary instructions regarding use of the product are necessary and adequately presented.

The FDA will be more likely to take action if the materials are false or misleading and, particularly, if the promotional activity presents a public health risk.

• Establish procedures for responding to requests regarding a product's off-label uses.

Unsolicited requests for off-label use information should be directed to, and handled by, the company's clinical/medical affairs unit, which should record items that are distributed in case the company must take corrective action at a later date.

• If you disseminate off-label information regarding a product, include the approved package insert and a disclaimer that the product is not approved for the off-label use and the material, given in its entirety, is for educational purposes.
• Ask the following questions before disseminating information about an off-label use:

a) Is an off-label use medically appropriate and effective?

b) Does the new use change the nature of the risk associated with the product?

c) Would using the product for

the off-label indication require special warnings?

d) Does it make economic sense for the company to promote the product for the off-label use, when potential liability issues are considered?

e) What is the larger corporate interest, beyond selling the product?

• Train employees about company policies (renegade salespeople can get the company into trouble).
• Remain vigilant in monitoring promotional activities.
• Have scientific substantiation for all off-label information disseminated, ideally from peer-reviewed medical journals or medical textbooks.
• Avoid excessive “puffing” in product advertising and sales brochures.
• Do not disseminate off-label information directly to consumers.

In conclusion, there is no question that off-label dissemination can improve sales. However, companies must consider the possible liability ramifications. It is better to think about it sooner, rather than later. In your office conference room, instead of a courtroom.

How is the dissemination of information regarding an unapproved indication for an approved drug or medical device like speeding on the highway? You might not get caught, but it can be dangerous and it might land you in court.

Most pharmaceutical and medical device companies promote their products for unapproved ' or off-label ' uses. The term “off-label” as used in this article refers to a situation in which the Food and Drug Administration (FDA) has approved or cleared the sale of a product for a particular indication, but a company markets it for a different use. Companies can make millions of dollars on off-label sales and, in some cases, the sales associated with off-label use are more profitable than sales associated with the authorized indication. Off-label promotion is a business reality. However, gains from off-label promotions can be quickly offset by costs associated with product liability litigation and the loss of good will within the medical and consumer communities.

Off-Label Use

Unless specific statutory and regulatory conditions described in the Food and Drug Administration Modernization Act and the FDA's implementing regulations are met (which are not discussed here), off-label dissemination is not legal. Many, if not most, companies that distribute materials to healthcare professionals about a product's off-label use do not strictly adhere to the law. After weighing projected increases in sales, along with competitive pressures, companies frequently take the risk associated with off-label promotion.

Companies, and the FDA, are familiar with several court decisions that have stymied the FDA's enforcement approach in the promotional area. Companies realize that the court decisions, as well as the FDA's limited resources when compared with the thousands of off-label promotional materials disseminated by or on behalf of the drug or device industry, mean that the FDA simply cannot, and will not, take regulatory action against all off-label promotion. Due to what is perceived by some as a hesitant FDA, many companies feel empowered to distribute aggressively off-label information with a sense of “FDA, catch me if you can.” However, such a strategy is short sighted and can result in disastrous product liability lawsuits that may result in financial and public relations nightmares.

By definition, “off-label” means that the promoted indication is not on the product's approved or cleared label. It does not necessarily mean that the use is unsafe or ineffective; the company may (and should) have substantiating data that the use is safe and effective. Because the off-label use is not “FDA-approved,” a company should recognize that, by disseminating off-label information, it increases its exposure to product liability claims.

In many cases, a company distributes off-label information to healthcare professionals. If, based on the dissemination, a doctor uses the product for the promoted off-label indication and an injury results, the company may be subject to a product liability claim. Even if the company can successfully defend itself using the learned intermediary doctrine or other legal principles, the company, with perceived deep pockets and insurance coverage, will no doubt find itself listed as a defendant in a product liability lawsuit.

Off-Label Litigation

An example of off-label promotion resulting in numerous product liability lawsuits involved bone screw implantable medical devices. The cases arose from injuries allegedly caused by orthopedic bone screw devices. Although the FDA had not authorized the devices for use in pedicle fixation surgery, manufacturers of the device allegedly actively promoted this use during seminars and other events. Approximately 5000 individuals filed suit against the manufacturers claiming injury from the devices. In Re Orthopedic Bone Screw Products Liability Litigation, 193 F.3d 781 (3d Cir. 1999). Although individuals cannot bring private causes of action against a company for violations of the Federal Food, Drug, and Cosmetic Act (FDC Act), the plaintiffs used the statute as a basis to argue that the manufacturers acted negligently through their promotion of unapproved uses. The manufacturers responded that the doctors used the devices in the course of their practice of medicine. The cases resulted in the manufacturers having to defend numerous claims in numerous states, each with its own set of laws.

Recommendations

The following are some recommendations for manufacturers to minimize product liability and regulatory risks.

1) Just Say No

Do not engage in any off-label promotion. Stick to the FDA-approved or cleared product labeling and file applications or supplements for new indications.

2) If You Do It …

• Comply with the FDA's requirements for off-label dissemination.
• Establish procedures that control the dissemination of off-label information before distribution (eg, an internal review checklist that requires sign off by appropriate personnel) and a team to review all promotional materials, regardless of the intended audience or the form of the promotion.

The team should include individuals from medical affairs, marketing, regulatory affairs, quality assurance, in-house counsel and, if appropriate, outside regulatory counsel.

The purpose of this review is to verify the accuracy of the information and claims about the product and to ensure that there are no implied or ambiguous representations.

Particular attention should be given to whether warnings or cautionary instructions regarding use of the product are necessary and adequately presented.

The FDA will be more likely to take action if the materials are false or misleading and, particularly, if the promotional activity presents a public health risk.

• Establish procedures for responding to requests regarding a product's off-label uses.

Unsolicited requests for off-label use information should be directed to, and handled by, the company's clinical/medical affairs unit, which should record items that are distributed in case the company must take corrective action at a later date.

• If you disseminate off-label information regarding a product, include the approved package insert and a disclaimer that the product is not approved for the off-label use and the material, given in its entirety, is for educational purposes.
• Ask the following questions before disseminating information about an off-label use:

a) Is an off-label use medically appropriate and effective?

b) Does the new use change the nature of the risk associated with the product?

c) Would using the product for

the off-label indication require special warnings?

d) Does it make economic sense for the company to promote the product for the off-label use, when potential liability issues are considered?

e) What is the larger corporate interest, beyond selling the product?

• Train employees about company policies (renegade salespeople can get the company into trouble).
• Remain vigilant in monitoring promotional activities.
• Have scientific substantiation for all off-label information disseminated, ideally from peer-reviewed medical journals or medical textbooks.
• Avoid excessive “puffing” in product advertising and sales brochures.
• Do not disseminate off-label information directly to consumers.

In conclusion, there is no question that off-label dissemination can improve sales. However, companies must consider the possible liability ramifications. It is better to think about it sooner, rather than later. In your office conference room, instead of a courtroom.