Off-Label Use Discussions Should Stay Off-line, FDA Draft Guidance Says

FDA advises companies to respond to unsolicited requests for off-label information in one-on-one dialogue; the agency also requests public comments on its policies regarding off-label communications in response to an industry citizen petition.

FDA is advising drug companies not to engage in online discussions about off-label uses of their products but to instead direct individuals posing questions to contact them directly.

The agency addresses Internet communications in a draft guidance on how manufacturers can respond to unsolicited requests for off-label information about prescription drugs and medical devices. The guidance pertains to all forms of public and non-public requests but devotes a great deal of attention to online communication. The document notes that because consumers increasingly use the Internet to search for information about medical conditions and treatments, companies may receive requests for information through product websites, discussion boards, chat boards and third-party websites.

The agency advises companies to respond online only to requests that pertain specifically to their named products and only to provide the firm’s contact information.

“The firm’s public response should convey that that the question pertains to an unapproved or uncleared use of the product and state that individuals can contact the medical/scientific representative or medical affairs department with the specific unsolicited request to obtain more information,” the guidance states.

FDA has yet to issue draft guidance on Internet and social media promotional activities but the guidance on how to respond to questions about off-label use suggests the agency may limit these communications as well. FDA had originally planned to issue some components of the social media guidance by the end of 2010 and then projected it would release a guidance in the first quarter of 2011 but failed to meet that goal as well (Also see "Internet-Focused Promotion, Warning Letters Both Up As FDA Guidance Nears" - Pink Sheet, 7 Mar, 2011.).

The off-label guidance states that because product information posted online is likely to be available to a broad audience for an indefinite period of time, “FDA is concerned that firms may post detailed public online responses to questions about off-label uses of their products in such a way that they are communicating unapproved or uncleared use information about FDA-regulated medical products to individuals who have not requested such information.”

“FDA is also concerned about the enduring nature of detailed public online responses to off-label questions because specific drug or device information may become outdated (e.g., new risk information may become available).”

In addition to providing a firm’s contact, the guidance says the company should include a mechanism for providing readily accessible current FDA-required labeling. An online response should include a direct link to the labeling and exclude links to other information. In addition, the guidance says that a web address directing viewers to labeling “should not itself be promotional in tone or content (e.g., should not be www.bestcancercure.com).”

An industry source knowledgeable about off-label use said the guidance appears to broaden the concept of scientific exchange to include consumers and patients, not just healthcare practitioners or scientists, while adhering to a restrictive policy on online discussions.

Company Should Narrow Broad Questions, Tailor Responses

The draft guidance is intended to update and clarify FDA’s policies on unsolicited requests for off-label information. It states that if a firm responds to these requests in the manner described in the draft guidance, “FDA does not intend to use such responses as evidence of the firm’s intent that the product be used for an unapproved or uncleared use.” In addition, the guidance says such responses would not be expected to comply with the disclosure requirements related to promotional labeling and advertising.

If firms respond in a manner other than that recommended in the draft guidance, “such activity would not constitute a per se violation of the law, but could potentially be introduced as evidence of a new intended use,” the document adds.

The guidance makes a distinction between solicited and unsolicited requests for information and between public and non-public requests. Public requests are those raised in public forums, including live presentations and electronic media.

In responding to non-public unsolicited requests for information, the guidance says information should be provided only to the individual making the request as a private, one-on-one communication. In addition, the information “should be tailored to answer only the specific question(s) asked.”

“If an unsolicited question is broad in nature, the firm should appropriately narrow the question,” the guidance states. “In other words, the level of specificity of the question posed is important to ensure that the firm’s response is tailored to the request.”

For example, the document says that if an individual requests information on use of a product for a disease or condition considered off-label (e.g., use of Drug X during pregnancy in patients with diabetes), then a firm generally should provide information pertaining only to that disease or condition (i.e., a response tailored only to the use of Drug X during pregnancy in patients with diabetes).

Firms Should Also Provide Contrary Data

The guidance also directs firms to include information about known or suspected risks associated with other diseases or conditions that is also relevant to the requested off-label information. For example, if Drug X is known to cause fetal harm when used in pregnant patients with arthritis, this risk information should be disclosed in the response about use of Drug X during pregnancy in patients with diabetes.

Further, the guidance says information distributed in response to an unsolicited request should be “truthful, non-misleading, accurate, and balanced.” Thus, a response should include data that are not supportive of an off-label use or cast doubt on the safety and efficacy of that use. And if the off-label use has been called into question by other articles or texts, the firm should disseminate representative publications that reach contrary or different conclusions about the off-label use.

The guidance says information distributed in response to a request should be accompanied by FDA-required labeling, a prominent statement that FDA has not approved the product as safe and effective for the use, statements disclosing the approved indications and safety information and a list of references for information included in the response.

FDA Requests Public Comments On Its Off-label Communications Policies

In a separate Dec. 28 Federal Register notice FDA announced that it is seeking comments on its policies on off-label communications about marketed products and products not yet legally marketed for any use. The action is in response to a citizen petition submitted in July on behalf of seven drug companies asking FDA to issue clarifying regulations in four areas of off-label communications (Also see "FDA Pressed To Clarify Permissible Formulary, Clinical Guideline Communications" - Pink Sheet, 5 Jul, 2011.).

“We have been considering what actions to take in the areas specified by the petitioners with respect to manufacturer responses to unsolicited requests; interactions with formulary committees, payors, and similar entities; and the dissemination of third-party clinical practice guidelines,” the agency states. To assist with its evaluation the agency “would like to obtain comments and information related to scientific exchange.”

FDA includes a list of questions it is particularly interested in getting feedback on, including how FDA should define scientific exchange, what types of activities do and do not fall under scientific exchange, what are the distinctions between scientific exchange and promotion, whether the identity of the participants should be given particular significance in determining whether an activity is a scientific exchange or a promotional activity, and how FDA should treat scientific exchange concerning uses of products that are not yet legally marketed.

Comments are due by March 27.