On 12 June 2018, the Food and Drug Administration (FDA) issued two final guidance documents providing feedback on acceptable means for drug and device makers to communicate certain types of product information to stakeholders. These guidance documents are the final versions of draft guidance documents issued on 18 January 2017, as we briefly discussed previously. The first final guidance, "Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities—Questions and Answers," (the Payor Guidance) provides FDA's views on manufacturer communications with payors (e.g., insurance companies, formulary committees and similar entities), including provision of healthcare economic information (HCEI) to payors under Section 502(a) of the Federal Food, Drug, and Cosmetic Act as amended by Section 3037 of the 21st Century Cures Act. The second final guidance, "Medical Product Communications That Are Consistent With the FDA-Required Labeling," (the Labeling Guidance) spells out how manufacturers can share truthful and non-misleading information that is not contained in the product labeling, but that is consistent with that labeling. While the differences between the draft and final guidance are fairly extensive, these two final guidance documents lay out a larger degree of flexibility and clarity for manufactures to engage in product information dissemination initiatives. Notably, FDA Commissioner Gottlieb stated in the Agency's announcement that the publication of these two final guidance documents is part of the Agency's "new efforts to advance medical product communications to support drug competition and value-based health care, "removing regulatory obstacles to value-based purchasing by payors," and "may help inform decision-making regarding patient care."
The Payor Guidance
The Payor Guidance provides recommendations as to how drug and device makers can communicate "truthful, non-misleading and appropriate" information particularly across the total lifecycle of their products. It emphasizes that it is important for manufacturers' communications to payors to be truthful and non-misleading with appropriate background and contextual information. The Agency believes, through the publication of this guidance, that the coverage decisions on new medical products will be sped up by enabling payors to review relevant information about unapproved products before they enter the market, recognizing that the payors are a sophisticated audience and closely scrutinize information about medical products as part of their decision-making process.
- The HCEI discussion in the Payor Guidance is now clearly defined to include both drug and device manufacturers, instead of drug manufacturers only.
- The HCEI definition is expanded and further clarified by adding the statement that "HCEI pertains to the economic consequences (including, but not limited to, monetary costs or resource utilization) related to the clinical outcomes of treating a disease (or specific aspect of a disease) or of preventing or diagnosing a disease."
- The Payor Guidance expands the safe harbor for preapproval communications to include an unapproved use of an approved/cleared/licensed product, in addition to a fully investigational product which has no approved, cleared or licensed uses.
- Communications of HCEI related to risk-sharing and value-based contracts are covered by the Payor Guidance, but FDA will not regulate the terms of contacts between the manufacturers and payors, and such contacts are not subject to FDA reporting requirements.
- When HCEI has material differences (e.g., new or increased risks, different dosing/use regimens, different endpoints, more limited/target patient populations, etc.,) from the FDA-approved labeling, the HCEI must present a conspicuous and prominent statement describing such differences.
- If an HCEI presentation is based on real-world data which falls outside of the recommended dosing regimen in the labeling, manufacturers are advised to use the statement "The dosing regimen used in this study varies from the dosing regimen in the FDA-approved labeling" together with the HCEI presentation and to utilize a font size comparable to that used for the other information in the presentation.
- FDA added "patient utilization projections (e.g., epidemiological data projection on incidence and prevalence) as a type of information that manufacturers can communicate and removed "targeting/marketing strategies".
- Once the prior information provided to payors becomes materially outdated, the manufacturers should provide updated information to payors.
- Manufacturers should include a clear statement that the product or use is not approved/cleared/licensed by FDA and that the safety or effectiveness of the product or use has not been established.
The Payor Guidance also provides a number of new illustrations of appropriate or inappropriate HCEI communications.
The Labeling Guidance
The Labeling Guidance details FDA's thinking through a set of 11 questions and answers. Overall, as Commissioner Gottlieb indicates in the FDA Announcement, FDA acknowledges the limitations of labeling in its effective communication of product information and notes that FDA-required labeling is "not intended to exhaustively address all that's known about a product for its approved or cleared uses." Therefore, FDA does not intend to rely on communications which are consistent with required labeling to establish a new intended use of a product if they meet FDA's three-factor test.
The three-factor test determines whether a communication is consistent with the FDA-required labeling:
- How does the information contained in the communication compare to information in the FDA-required labeling?
- Does the information in the communication about the use of the product increase the potential for harm to health relative to the information in the FDA-required labeling?
- Does the condition of use in FDA-required labeling enable the product to be used safely and effectively for the conditions of use described in the communication?
If a product communication fails to satisfy any one of these factors, it is not considered consistent with the FDA-required labeling. The Labeling Guidance sets forth several examples which illustrate application of the three-factor test.
Although FDA states the Labeling Guidance is useful to guide manufacturers in conveying information in a truthful and non-misleading way, device manufacturers of 510(k) and 510(k)-exempt devices should not restrict themselves to the three-factor test. With respect to 510(k)-cleared devices, FDA recommends analyzing communications in accordance with 21 C.F.R. § 807.81(a)(3) and FDA's guidance Deciding When to Submit a 510(k) for a Change to an Existing Device to decide if communications are consistent or not. For 510(k)-exempt devices, FDA recommends that manufacturers analyze communications in accordance with the limitations of exemptions in the device classification regulations to decide if communications are consistent or not.
Per the Labeling Guidance, communications consisting of data, studies, and analyses must be based on scientifically appropriate and statistically sound standards. In addition, per the guidance, manufacturers must not inflate the findings or fail to disclose the limitations of the studies or analyses. For example, information based on speculation or belief, as well as based on a poorly designed or conducted studies or analyses, would not meet the standard.
Both guidance documents lend valuable additional clarity to drug and device manufacturers regarding their product communications. Manufacturers should proactively engage their counsels and responsible functional units to thoroughly consider the application of the two guidance documents to their current business, and if necessary, carefully revise the internal compliance practices or programs, to take advantage of them.