FDA Releases Draft Guidance on Communications from Firms to Health Care Providers Regarding Specific Information on Unapproved Uses of Approved/Cleared Medical Products

On October 23, 2023, the U.S. Food and Drug Administration (“FDA” or “the Agency”) issued a revised draft guidance for industry entitled Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers (“SIUU Communications Draft Guidance”).[1]

This client alert summarizes the key points in FDA’s SIUU Communications Draft Guidance, noting shifts or expansions in FDA policy. Compared to prior guidance on this topic, the SIUU Communications Draft Guidance covers new types of scientific communications about unapproved uses of approved/cleared medical products, including independent clinical practice resources and firm-generated presentations of scientific information from an accompanying published reprint. But it also establishes new, and oftentimes ambiguous, requirements that may restrict firms’ ability to communicate such information.

The SIUU Communications Draft Guidance is a continuation of FDA’s efforts to refine its policies and recommendations relating to communications by firms about unapproved uses of their approved/cleared medical products. In 2009, the Agency published draft guidance entitled Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices. FDA released a revised version of that draft guidance in 2014, entitled Distributing Scientific and Medical Publications on Unapproved New Uses — Recommended Practices (“Revised Good Reprint Practices Draft Guidance”). When finalized, the SIUU Communications Draft Guidance will replace the Revised Good Reprint Practices Draft Guidance.

The SIUU Communications Draft Guidance addresses communications by firms (including, among other entities, sponsors and manufacturers of medical products) to health care providers (“HCPs”) about “scientific information on unapproved use(s)” (“SIUU”) of approved/cleared medical products. FDA limits the scope of the SIUU Communications Draft Guidance to three types of information that may be shared by firms with HCPs: (1) published scientific or medical journal articles (“reprints”); (2) published clinical reference resources, which include clinical practice guidelines (“CPGs”), scientific or medical reference texts (“reference texts”), and materials from independent clinical practice resources; and (3) firm-generated presentations of scientific information derived from an accompanying published reprint. The Good Reprint Practices Draft Guidance likewise covers the first and most of the second type of information (including CPGs and reference texts); however, the second type is broadened in the SIUU Communications Draft Guidance to include independent clinical practice resources, and the third type is entirely new.

There are a number of additional key differences in scope between the Good Reprint Practices Draft Guidance and this new SIUU Communications Draft Guidance:

• Whereas the Good Reprint Practices Draft Guidance permits distribution of materials that discuss unapproved uses of approved/cleared medical products to both HCPs and “health care entities” (including hospitals, professional medical organizations, drug formulary committees, pharmacy benefits managers, health insurance issuers, group health plans, and Federal or State governmental agencies involved in the provision of health care or health insurance), the SIUU Communications Draft Guidance covers communications to HCPs only.
• While the Revised Good Reprint Practices Draft Guidance relates only to human medical products (drugs, biologics, and devices), the SIUU Communications Draft Guidance covers human medical products and animal drugs.
• Similar to the Good Reprint Practices Draft Guidance, the SIUU Communications Draft Guidance explains that SIUU communications should be truthful and non-misleading. But the SIUU Communications Draft Guidance goes further in stating that SIUU communications should also be factual and unbiased and provide all information necessary for HCPs to interpret the strengths, weaknesses, and validity of the information in the communication. These new expectations are not clearly defined in the SIUU Communications Draft Guidance.

The SIUU Communications Draft Guidance announces the following “enforcement policy”: Where a firm’s communications comply with the requirements in the SIUU Communications Draft Guidance, FDA does not intend to use such communications alone as evidence of a new intended use. The SIUU Communications Draft Guidance does not clarify whether FDA considers this enforcement policy to be an exercise of enforcement discretion or a legal interpretation that compliant SIUU communications are not regulated promotional speech.

FDA repeatedly notes throughout the SIUU Communications Draft Guidance its attempt to strike a careful balance between competing interests: on the one hand, the interests of HCPs in information about unapproved uses of approved medical products to inform clinical practice decisions; on the other hand, government interests such as ensuring satisfaction of premarket requirements and protecting patients from medical product uses that have not been shown to be safe and effective. Left open is whether FDA’s proposed restrictions on firms’ SIUU communications are consistent with the First Amendment.

The SIUU Communications Draft Guidance states that it does not address other types of communications to HCPs, including responses to unsolicited requests, presentations at medical conferences, or discussions that are consistent with the FDA-approved labeling. As noted above, the SIUU Communications Draft Guidance also does not apply to communications to payors.

The SIUU Communications Draft Guidance includes lengthy responses to four questions on the following topics: (1) appropriateness of source publications, (2) information to include in SIUU communications, (3) presentational considerations for SIUU communications, and (4) recommendations for specific types of SIUU communications.

A. Appropriateness of source publications as the basis for SIUU communications

The SIUU Communications Draft Guidance establishes a new standard for source publications that serve as the basis for SIUU communications. Firms should ensure that source publications describe studies or analyses that are “scientifically sound” and provide “clinically relevant information.” Although FDA provides general guidance on these concepts, the SIUU Communications Draft Guidance does not precisely define this new standard or explain how it differs from standards for other manufacturer communications (e.g., communications that are consistent with the FDA-required labeling, which are expected to be “scientifically appropriate and statistically sound” under FDA’s 2018 guidance entitled Medical Product Communications That Are Consistent With the FDA-Required Labeling — Questions and Answers). To be scientifically sound in the context of the SIUU Communications Draft Guidance, the studies and analyses should, at a minimum, meet generally accepted design and other methodological standards for the particular type of study or analysis performed. To be clinically relevant, the studies or analyses should provide information that is pertinent to HCPs making clinical practice decisions for the care of an individual patient.

The SIUU Communications Draft Guidance provides further detail on the types of studies likely to produce scientifically sound results and clinically relevant data. For drugs, these studies include randomized, double-blind, concurrently controlled superiority trials. For medical devices, they include studies that are considered valid scientific evidence as described in 21 C.F.R § 860.7 (e.g., well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device). However, other sources, including real-world data and real-world evidence, could generate scientifically sound and clinically relevant information as well.

By contrast, studies without an adequate comparison or control group, isolated case reports, reports that lack enough detail to permit scientific evaluation, distorted studies, and studies based on fraudulent data would generally not be scientifically sound or clinically relevant. Notably, FDA also expresses doubt that scientific data generated in early stages of medical product development would be sufficiently reliable to allow for a determination of clinical relevance.

FDA also recommends that manufacturers remove from the internet any SIUU communications that are no longer reliable.

B. Information that firms should include as part of SIUU communications

The SIUU Communications Draft Guidance lists various information that firms should include as part of SIUU communications. These include:

1. a statement that the unapproved use(s) of the medical product has not been approved and that the safety and effectiveness has not been established;
2. a statement disclosing the FDA approved use(s) (including limitations of use described in the labeling);
3. a statement disclosing any limitations, restrictions, cautions, or warnings described in the labeling about the unapproved use(s);
4. a copy of the most current labeling;
5. a statement describing any contraindications in the labeling;
6. a statement describing any serious risks relevant to the unapproved use(s) that are in the labeling or known by the firm;
7. a statement identifying any authors, editors, or other contributors to publication(s) included in the communication who were employees of or consultants to the firm at the time of writing, if reasonably known by the firm;
8. where the SIUU communication is based on a particular study, a description of material aspects and limitations of study design, methodology, and results, as well as any contrary or differing conclusions from other relevant studies; and
9. the publication date of any references or included publications.

C. Presentational considerations that firms should take into account for SIUU communications

FDA outlines several other restrictions for firms to consider in presenting SIUU communications to HCPs:

1. SIUU communications should clearly and prominently present all disclosures recommended in the SIUU Communications Draft Guidance: Like the Good Reprint Practices Draft Guidance, the SIUU Communications Draft Guidance recommends that all necessary disclosures be clearly and prominently presented. For example, for SIUU communications that have both audio and visual components, FDA recommends that disclosures be presented in both the audio and text simultaneously, using the same words.
2. SIUU communications should not use persuasive marketing techniques: FDA expresses concern about firms’ use of “persuasive marketing techniques” in SIUU communications. Such techniques, according to FDA, influence the use of medical products for non-scientific reasons. Although FDA provides a few examples of “persuasive marketing techniques”—celebrity endorsements, premium offers, and gifts—the SIUU Communications Draft Guidance does not define this new term or describe communications the Agency would consider inappropriate.
3. SIUU communications should be separate and distinct from promotional communications about approved uses of medical products: Like the Good Reprint Practices Draft Guidance, the SIUU Communications Draft Guidance recommends that firms separate and distinguish SIUU communications from promotional communications about approved uses of medical products. Specifically, where possible, FDA recommends that firms use dedicated vehicles, channels, and venues for sharing SIUU communications that are separate from those used for promotional communications about approved uses of medical products, so as to reduce the risk that HCPs will conflate information about approved versus unapproved uses. For example, FDA recommends that firms clearly separate and distinguish promotional communications about approved uses of a medical product versus SIUU communications in webpages, in emails, and at booths in commercial exhibit halls at medical or scientific conferences. The SIUU Communications Draft Guidance does not address which sorts of field personnel may deliver SIUU communications (for example, sales representatives versus medical affairs personnel).
4. SIUU communications should be shared through media and via platforms that enable firms to implement the recommendations in the SIUU Communications Draft Guidance: FDA notes that certain online platforms would not enable a firm to include all recommended disclosures within their SIUU communications. For example, the SIUU Communications Draft Guidance explains that platforms that impose character-space or other presentational limitations should not be used to host SIUU communications, although they could be used to direct HCPs to an SIUU communication.
5. Firms should consider using plain language in the content they develop for SIUU communications to facilitate comprehension: The SIUU Communications Draft Guidance directs firms to consider using plain language in their SIUU communications to facilitate comprehension. This directive is motivated by concern that HCPs may have difficulty understanding some types of scientific information, including clinical trial data and the design and methodological limitations of studies. Specifically, FDA recommends that SIUU communications be clear, concise, well-organized, and where possible, avoid complexities such as technical jargon, passive voice, and long sentences and paragraphs.

D. Additional recommendations for specific types of SIUU communications

The SIUU Communications Draft Guidance provides additional recommendations for the different types of SIUU communications, including the new sub-category of independent clinical practice resources and the new category of firm-generated presentations of scientific information from an accompanying reprint.

FDA defines an “independent clinical practice resource” as a digital resource that contains medical and scientific information on a wide range of topics developed by subject matter experts in various medical specialty fields. According to the SIUU Communications Draft Guidance, the information in an independent clinical practice resource is typically searchable by topic or keyword and produces materials in response to an HCP’s search terms. When firms share SIUU communications in the form of independent clinical practice resources (as well as reference texts), FDA recommends that they be:

1. published by an independent publisher that is in the business of publishing scientific or medical educational content;
2. published in a manner consistent with current standards for medical content creation and review that are generally accepted by the medical publishing industry and in accordance with any specific peer-review procedures of the publisher;
3. authored, edited, and contributed to by experts who have demonstrated expertise in the subject area(s) through education or experience; and
4. generally available or sold through independent distribution channels (e.g., internet sources, book retailers, subscriptions, libraries) for medical and scientific educational content.

For the new category of firm-generated presentations of scientific information from an accompanying reprint, the SIUU Communications Draft Guidance similarly does not shed light on the kinds of communications that would be considered appropriate firm-generated presentations (e.g., whether it includes a range of potential media and formats). Notwithstanding this ambiguity, FDA outlines several recommendations for this type of SIUU communications. Specifically, FDA recommends that the full reprint(s) should accompany the presentation, but FDA also emphasizes that all material information should be included within the firm’s presentation. Additionally, the presentation should include the recommended disclosures and specify which portions are firm-generated.

FDA also recommends against several practices with respect to firm-generated presentations, explaining that firms should not:

1. imply that the information from the reprint(s) represents larger or more-general experience with the medical product than it actually does;
2. present information from the reprint(s) out of context;
3. include suggestions about the safety or effectiveness of the medical product for the unapproved use(s) that are not consistent with the reprint;
4. present conclusions or representations about safety or effectiveness for the unapproved use (even if an accurate reflection of the statements in the reprint) without attributing that statement to the reprint and without immediately following it with disclosures regarding any relevant relationships with authors, editors, or other contributors to the reprint(s);
5. use statistical techniques to indicate clinical significance or validity of a finding not supported by the reprint; or
6. use presentational elements to distort or misrepresent the outcomes evaluated in the reprint.

The comment period for the SIUU Communications Draft Guidance offers firms the opportunity to provide input on important aspects of FDA’s framework regarding scientific communications about unapproved uses of approved/cleared medical products. Although stakeholders may comment on any FDA guidance at any time, see 21 C.F.R. § 10.115(g)(5), comments on the SIUU Communications Draft Guidance should be submitted by December 26, 2023—as set forth in the Federal Register notice, 88 Fed. Reg. at 73034—to ensure FDA’s consideration.

The Federal Register Notice explains FDA’s interest in additional matters related to SIUU communications. Specifically, FDA is seeking stakeholder input on two questions:

1. “What considerations, if any, exist that are unique to communications of scientific information about unapproved use(s) of approved/cleared medical products by firms to researchers (including HCPs working in their capacity as researchers)?”
2. “What other factors should firms consider when sharing firm-generated presentations (as described in the draft guidance) to ensure that presentations are truthful, non-misleading, factual and unbiased and provide all information necessary for HCPs to interpret the strengths and weaknesses and validity and utility of the presented information?”

If you have any questions concerning the material discussed in this client alert, please contact the members of our Food, Drug, and Device practice.