Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers
Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers
<!-- page 1 -->Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities
Questions and Answers Guidance for Industry
DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.
Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit electronic comments to <u>
</u>. Submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.
For questions regarding this draft document, contact (CDER) Twyla Mosey, 301-796-1200; (CBER) Office of Communication, Outreach and Development, 800-835-4709 or 240-402-8010; (CDRH) Stephanie Philbin, 301-837-7151.
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Center for Devices and Radiological Health (CDRH)
June 2026 Procedural Revision 1
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Questions and Answers Guidance for Industry
Additional copies are available from:
Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration
Phone: 855-543-3784 or 301-796-3400
Email: <u>
</u></span>
<u>https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs
</u></span>
and/or
Office of Communication, Outreach and Development Center for Biologics Evaluation and Research Food and Drug Administration
Phone: 800-835-4709 or 240-402-8010; Email: <u>
industry.biologics@fda.hhs.gov
</u></span>
and/or
Office of Policy
Center for Devices and Radiological Health Food and Drug Administration
10903 New Hampshire Ave., Bldg. 66, Room 5441
Silver Spring, MD 20993-0002
Email: <u>
</u></span>
</u><u>medical-devices-and-radiation-emitting-products</u>
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Center for Devices and Radiological Health (CDRH)
June 2026 Procedural Revision 1
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TABLE OF CONTENTS
I. INTRODUCTION II. BACKGROUND III. QUESTIONS AND ANSWERS A. Communications of HCEI by Firms to Payors Regarding Approved/Cleared Medical Products B. Communications by Firms to Payors Regarding Unapproved Medical Products and Unapproved Uses of Approved/Cleared Medical Products
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Questions and Answers
Guidance for Industry
This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page.
I. INTRODUCTION
This guidance provides answers to common questions concerning firms’ communication of health care economic information (HCEI) regarding their prescription drugs and medical devices to payors, formulary committees, or other similar entities with knowledge and expertise in the area of health care economic analysis (collectively referred to as payors). This guidance also addresses common questions relating to dissemination to payors of information about medical products that are not yet approved or cleared for any use (collectively referred
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to as unapproved medical products<sup>9)</sup> and dissemination to payors of information about unapproved uses of approved/cleared medical products.
This guidance incorporates updates to the Federal Food, Drug, and Cosmetic Act (FD&C Act) as amended by section 3630 of the Consolidated Appropriations Act, 2023 and will replace the final guidance for industry and review staff of the same title issued in June 2018 when finalized. Changes from the final guidance include updates to reflect revised statutory text that makes the provisions in section 502(a) of the FD&C Act ( U.S.C. 352(a)) regarding communication of HCEI to payors applicable to devices. This guidance also includes updates to align its recommendations with the new section 502(gg) of the FD&C Act, which provides that “no drug or device shall be deemed to be misbranded” under section 502(f)(1) ( U.S.C. 352(f)(1)) because of certain truthful and not misleading information provided to payors. Section 502(gg) applies to information about investigational medical products and investigational uses of medical products that are approved, cleared, granted marketing authorization, or licensed under section 36 505 ( U.S.C. 355), 510(k) ( U.S.C. 360(k)), 513(f)(2) ( U.S.C. 360c(f)(2)), or 515 ( U.S.C. 360e) of the FD&C Act or section 351 of the PHS Act ( U.S.C. 262) (as applicable). Section III.B of this guidance applies to information about all unapproved medical products and unapproved uses of approved/cleared medical products. In addition, editorial and organizational changes have been made to improve clarity.
The questions and answers are grouped in the following categories:
* Communications of HCEI to payors regarding approved/cleared medical products
* Communications to payors about unapproved medical products and about unapproved uses of approved/cleared medical products
In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of
marketing authorization under section 513(f)(2) of the FD&C Act; humanitarian device exemption approval under section 520(m) of the FD&C Act; or exemption from premarket notification. Similarly, the term approved/cleared also applies to a device that is licensed as a biological product under section 351 of the PHS Act (see footnote 5).
<!-- page 6 -->the word should in Agency guidances means that something is suggested or recommended, but not required.
II. BACKGROUND
As referenced above, a number of FDA’s statutory and regulatory provisions potentially impact firms’ communications with payors. This guidance provides FDA’s thinking on frequently asked questions regarding such communications in order to provide clarity to firms and payors.
Payors are a sophisticated audience with a range of expertise in multiple disciplines, as well as established procedures for carefully considering evidence about medical products. Generally, payors possess the financial resources and motivation to closely scrutinize information about medical products as part of their decision-making process, including an evaluation of the limitations and reliability of that information. Payors seek a range of information on the effectiveness, safety, and cost-effectiveness of approved/cleared medical products, including information from firms, to help support their product selection, formulary management, and/or coverage and reimbursement decisions on a population basis. Often, this information differs from — and can be provided in addition to — the information FDA reviews in making approval/clearance decisions.
HCEI and product information provided by firms to payors about their medical products must be truthful and not misleading. This guidance provides FDA’s recommendations for firms to help them ensure that their communication of HCEI to payors about approved/cleared medical products is truthful and not misleading. Specifically, section III.A of this guidance provides FDA’s thinking on frequently asked questions regarding communication of HCEI to payors about approved/cleared medical products under section 502(a) of the FD&C Act (21 U.S.C. 79 352(a)). FDA considers firms’ communications of HCEI to payors that otherwise meet the definition under section 201(m) of the FD&C Act (21 U.S.C. 321(m)) to be labeling.
https://www.congress.gov/committee-report/105th-congress/senate-report/43/1
</u>), and that under “FDA’s current postmarketing reporting regulations, health care economic information as defined in this section must be submitted to the FDA at the time it is initially provided to a formulary committee or other similar entity” (see page of the House Report on the Prescription Drug User Fee Reauthorization and Drug Regulatory Modernization Act of 1997 (H.R. 1411), H.R. Rep. No. 105-310, available at <u>
https://www.congress.gov/committee-report/105th-congress/house-report/310
</u>. The referenced postmarketing reporting requirements apply to drug promotional
<!-- page 7 -->Payors have also indicated that in some situations, due in part to their need to plan for and make coverage and reimbursement decisions far in advance of the effective date of such decisions, they are also interested in receiving information from firms about medical products that are not yet approved/cleared by FDA for any use and information about unapproved uses of approved/cleared medical products. Firms’ communications regarding unapproved medical products and unapproved uses of approved/cleared medical products raise a number of potentially competing public health interests. FDA’s approach to implementation of its authorities in this area seeks to balance these interests to best advance the public health overall.
Some firms’ communications regarding unapproved medical products or unapproved uses of approved/cleared medical products may undermine substantial government interests related to health and safety. These interests include:
* Motivating the development of robust scientific data on safety and effectiveness
* Maintaining the premarket review process for safety and effectiveness of each intended use in order to prevent harm; to protect against fraud, misrepresentation, and bias; and to develop appropriate instructions for use for medical products
* Protecting the integrity and reliability of promotional information regarding medical product uses
* Preventing the diversion of health care resources toward ineffective treatments
FDA recognizes that in certain instances, there can be tension between the public health interests directly advanced by the premarket review requirements and other important interests. For example, as previously discussed, FDA recognizes that in some situations, payors need to plan for and make coverage and reimbursement decisions for medical products and uses far in advance of the effective date of such decisions. In making decisions on a population basis, payors can draw on a range of expertise in multiple disciplines that allows them to critically evaluate information presented to them by firms, including an evaluation of the limitations and reliability of that information. FDA recognizes the value of payors receiving truthful and not misleading information about unapproved medical products and unapproved uses of approved/cleared medical products, as described in section 502(gg) of the FD&C Act, in order to inform their decision-making.
Section III.B of this guidance provides FDA’s thinking on frequently asked questions regarding communications to payors about unapproved medical products and about unapproved uses of approved/cleared medical products. Firms’ communications to other audiences about
labeling (as well as to advertisements) (see 21 CFR 314.81(b)(3)(i)). Because Congress sought to address the use of HCEI in the context of these promotional materials, and firms have disseminated this information through promotional labeling materials, FDA’s longstanding approach has been to consider communication of HCEI about drugs under this section to be promotional labeling. See also Q9. The Agency similarly considers communications of HCEI about devices to be promotional labeling.
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unapproved medical products or unapproved uses of approved/cleared medical products are beyond the scope of this guidance.
III. QUESTIONS AND ANSWERS
A. Communications of HCEI by Firms to Payors Regarding Approved/Cleared Medical Products
Q1. What is HCEI, and how can it be presented?
HCEI is defined in section 502(a)(2)(A) of the FD&C Act as “any analysis (including the clinical data, inputs, clinical or other assumptions, methods, results, and other components underlying or comprising the analysis) that identifies, measures, or describes the economic consequences, which may be based on the separate or aggregated clinical consequences of the represented health outcomes, of the use of a drug or device. Such analysis may be comparative to the use of another drug or device, to another health care intervention, or to no intervention.” 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. HCEI, for example, may include comparative analyses of the economic consequences of a medical product’s clinical outcomes to alternative options (including the use of another medical product) or to no intervention.
HCEI can be presented in a variety of ways that can include but are not limited to an evidence dossier, a reprint of a publication from a peer-reviewed journal, a software package comprising a model with a user manual, a budget-impact model, a slide presentation, or a payor brochure.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents
</u>.
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Q2. What is the appropriate scope of the audience for the communication of HCEI about approved/cleared medical products under section 502(a)?
Section 502(a) specifies that HCEI can be provided to “a payor, formulary committee, or other similar entity with knowledge and expertise in the area of health care economic analysis, carrying out its responsibilities for the selection of drugs or devices for coverage or reimbursement.”
This audience includes public and private sector payors, formulary committees (e.g., pharmacy and therapeutics committees), drug information centers, technology assessment committees, pharmacy benefit managers, third party administrators, and other multidisciplinary entities that, on behalf of health care organizations, review scientific and/or technology assessments to make medical product selection or acquisition, formulary management, and/or coverage and reimbursement decisions on a population basis.
Such entities are constituted to consider HCEI (and other types of information) through a “deliberative process” and should have the appropriate range of “knowledge and expertise in the area of health care economic analysis” needed to interpret HCEI presented to them to inform their population-based decision-making process.<sup>22,23</sup> Expertise in this area is critical to understand and evaluate health care economic analyses and their limitations.
Because section 502(a) provides for communication of HCEI only to particular audiences, dissemination of HCEI to other audiences is not covered by the recommendations of this guidance. Thus, this guidance does not apply to dissemination of HCEI to other audiences, such as health care providers who are making individual patient prescribing decisions or
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consumers (e.g., dissemination directed toward prescribers or consumers via a public website). This is not meant to suggest that individuals who have multiple roles, such as a health care provider who serves on a formulary committee and also provides care for individual patients, would not fall within the scope of the appropriate audience for this guidance when they are carrying out their professional responsibilities for selection of medical products for coverage or reimbursement for a payor, formulary committee, or similar entity.
Q3. How does FDA intend to implement this guidance for HCEI disseminated in accordance with section 502(a)?
Section 502(a) provides that HCEI disseminated in accordance with the terms of that statutory provision is not false or misleading. If a firm disseminates to an appropriate audience HCEI that is of the type of information described in section 502(a), i.e., HCEI that relates to an approved indication and is based on competent and reliable scientific evidence (CARSE), as each of these elements is described in this guidance, FDA does not intend to consider such information false or misleading.
HCEI should clearly and prominently present the information discussed in Q7 and Q8 of this section, including study design and methodology, generalizability, limitations, sensitivity analyses, and information relevant to providing a balanced and complete presentation. If HCEI includes material differences from the FDA-approved labeling (e.g., new or increased risks, different dosing/use regimens, different endpoints, more-limited/targeted patient populations), it must present "a conspicuous and prominent statement describing any material differences between the health care economic information and the labeling approved for the drug or device," as discussed in Q7.
In addition, FDA does not intend to use HCEI that is disseminated consistent with this guidance, standing alone, as evidence of a new intended use.
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Q4. Section 502(a) provides that HCEI shall not be considered false or misleading if, among other things, it "relates to an [approved] indication." What types of information does FDA consider to relate to an approved indication?
To be considered related to an approved indication, HCEI analyses should relate to the disease or condition, the manifestation of the disease or condition, or symptoms associated with the disease or condition in the patient population for which the medical product is indicated in the FDA- approved labeling.
The table below provides examples of HCEI analyses that FDA believes could be considered related to an approved indication of a medical product, despite incorporating information that does not appear within — and may vary in certain respects from — information presented in the FDA-approved labeling. These examples are for illustrative purposes only and are not intended to be comprehensive or restrictive.
<u>Examples of HCEI</u> Analyses That Relate to an Approved Indication
| Example | Description |
|---|---|
| Duration of treatment | Where the approved indication for a medical product does not limit the duration of use, HCEI analyses may incorporate information about the long-term use of the medical product for that indication over a period that is different from that addressed in the studies described in the FDA-approved labeling (e.g., if a medical product is approved for a chronic condition with no limitation on its duration of use based on 24-week studies, economic consequences beyond 24 weeks can be modeled). |
| Health care setting | HCEI analyses may be based on use of the medical product for its approved indication in health care settings that differ from the settings of the clinical trials submitted to FDA in the application (e.g., results of clinical trials conducted only in a fee-for-service setting could be extrapolated to a managed care or other setting, or results of clinical trials conducted in a hospital center could be extrapolated to an ambulatory care setting). |
| Burden of illness | HCEI analyses may be derived from studies of the burden of a disease for which the medical product is indicated, including economic consequences |
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| Example | Description |
|---|---|
| of the effect the treatment has on clinical outcomes (e.g., economic consequences of absent work days as a result of signs and symptoms associated with a disease). | |
| Dosing/use regimen | HCEI analyses may be based on data or studies of a medical product for its approved indication, where the dosing/use regimen varies from the FDA-approved labeling (e.g., an observational study based on real-world drug utilization data from a health plan database or the electronic health records of a hospital system, where actual patient use of an approved dosage form and strength of a drug for an approved indication falls outside the recommended dosing/use regimen in the label, such as by taking at a different frequency or a different total dose than recommended). |
| Patient subgroups | HCEI analyses may be derived from analyses of treatment effects in patient subgroups (e.g., demographics, disease severity, co-morbidities), including subgroups with response rates that may vary from the rates reflected in the FDA-approved labeling, that are within the patient population for the approved indication, even if these subgroup analyses were not pre-specified in the studies that formed the basis for approval of the medical product. |
| Length of hospital stay | HCEI analyses may be derived from studies of treatment impacts on length of hospital stay. |
| Surrogate or intermediate endpoints | HCEI analyses may be derived from clinical data demonstrating an effect on a surrogate endpoint that is known to predict clinical benefit (i.e., a validated surrogated endpoint) or on a surrogate or intermediate clinical endpoint that is reasonably likely to predict clinical benefit.²⁸ |
| Clinical outcome assessments or other health outcome measures | HCEI analyses may be derived from studies involving the approved indication of a medical product that assess clinical outcome assessments (COAs)²⁹ (e.g., patient-reported outcomes such as work productivity, basic activities of daily living) or other health outcome measures (e.g., quality- |
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| Example | Description |
|---|---|
| adjusted life years (QALYs))³⁰ when they are evaluated using valid and reliable measures (as determined by experts who are familiar with evaluating the merits of a particular COA or other health outcome measure). | |
| Compliance/ adherence | HCEI analyses may be derived from studies assessing patient compliance/adherence³¹ with a medical product for its approved indication. |
| Persistence | HCEI analyses may be based on data estimating patient persistence³² on a medical product for its approved indication (e.g., estimates based on medical product utilization data from a health plan database). |
| Comparisons | HCEI analyses may be derived from studies comparing the safety or effectiveness of a medical product for its approved indication to another medical product or intervention or to no treatment. |
The following are examples of HCEI analyses that are not considered to relate to an approved
indication:
* If a medical product is approved only to relieve the symptoms of a disease, HCEI
analyses regarding use of the medical product to prevent, cure, or mitigate/change the
course of the disease would not be considered related to the medical product’s
approved indication. For example, if an analysis for a medical product indicated for
pain management in cancer patients discussed the medical product’s effect on
delaying the progression of cancer or prolonging patient survival (disease course
modification), FDA would not consider this to relate to the approved indication.
* HCEI analyses derived from studies limited to patient populations that are not within
the indicated patient population are not related to the approved indication of the
medical product. For example, if a medical product is approved only for use in
<!-- page 14 -->patients in a certain age group, an analysis regarding the treatment of only patients outside of that age group would not be considered to relate to the approved indication for the medical product.
Q5. What evidentiary support should firms have for their HCEI under section 502(a)?
Section 502(a) states that HCEI shall not be considered false or misleading if, among other things, it is “based on competent and reliable scientific evidence.” FDA considers HCEI to be based on CARSE if the HCEI has been developed using generally accepted scientific standards that are appropriate for the information being conveyed and that yield accurate, reliable results. In evaluating whether the amount and type of evidence that forms the basis for a particular communication of HCEI meets the generally accepted scientific standards for such information, FDA will consider existing current good research practices for substantiation developed by authoritative bodies. Examples of such bodies include but are not limited to the International Society for Pharmacoeconomic and Outcomes Research (ISPOR), the International Society for Pharmacoepidemiology (ISPE), the Patient-Centered Outcomes Research Institute (PCORI), and the Agency for Healthcare Research and Quality (AHRQ). For example, when evaluating HCEI based on indirect treatment comparisons in the absence of data from head-to-head controlled clinical trials, FDA may refer to guidelines issued by external expert bodies regarding current rigorous methodologies and best practices for such comparisons (e.g., network meta-analyses).
HCEI should clearly and prominently present the applicable information discussed in Q7 and Q8 of this guidance, including study design and methodology, generalizability, limitations, sensitivity analyses, and information relevant to providing a balanced and complete presentation.
Q6. Does the CARSE standard apply only to the economic components of HCEI, or does it also apply to the other components?
Under section 502(a), HCEI includes the “clinical data, inputs, clinical or other assumptions, methods, results, and other components underlying or comprising the analysis” of a medical product’s economic consequences. FDA considers the CARSE standard in section 502(a) to apply to all components of HCEI, including inputs and assumptions related to both economic consequences and clinical outcomes (i.e., safety and/or effectiveness). As discussed previously in Q4, such information must also relate to an approved indication in order to fall within the provisions of section 502(a) regarding HCEI.
Q7. What information should firms include when disseminating HCEI?
To enable payors to make informed coverage and reimbursement decisions, firms should include appropriate background and contextual information when disseminating HCEI. Included below are examples of the types of background and contextual information that may be material to HCEI presentations; some of these categories of information may not be applicable to particular HCEI presentations. This information, where relevant, should be presented clearly and prominently. The disclosure of the pertinent information can be concise so long as all material information is provided (such as the source(s) of data used, the outcome measures used, the type of analysis, the limitations of the analysis, and the generalizability of the findings), as further
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described below. FDA recommends that this contextual information be presented in conjunction with the information within the HCEI presentation to which it relates or that the HCEI presentation includes a prominent reference to where the information can be found within the presentation.
FDA is aware that some authoritative bodies have developed format recommendations for firms’ communications to payors, which include recommendations for where firms should disclose the information described below within their communications. The recommendations provided here are not meant to suggest that firms should make duplicative disclosures of this background/contextual information if it is already provided in accordance with such format recommendations.
- Study Design and Methodology
Firms should include an accurate overview of the design of the economic analysis, including a statement of the study objectives. For example, a clear description of the hypothesis tested should be provided, and potential biases and/or confounders should be acknowledged. In addition, the following information about the study and/or methodology should be presented where relevant:
Type of Analysis: The type of economic analysis selected (e.g., cost-minimization analysis, cost-effective analysis, cost-utility analysis, cost-benefit analysis, cost-consequence analysis, budget impact analysis) should be stated, and the reason for its choice should be explained (Drummond and Jefferson 1996).
Modeling: The type of modeling technique should be disclosed, with an explanation of the model choice, its scope, and its key variables/parameters (Husereau et al. 2013). The rationale and consequences of including and excluding specific variables in economic models should be discussed in the analysis.
Patient Population: Details about the patient population should be specified, including the number of patients and relevant demographic information, such as age, sex, race, clinical characteristics, and socioeconomic status (Gold et al. 1996; Husereau et al. 2013).
Perspective/Viewpoint: The perspective or viewpoint of the economic analysis should be clearly stated so that payors can understand the rationale for the selection of inputs (e.g., outcome measures, time periods, costs) and can therefore determine whether the HCEI is relevant to their particular health care organizations. Possible viewpoints can include those of the patient, employer, health care provider (e.g., clinician, institution), payor, regulatory body (e.g., government agency), or society (i.e., everyone impacted by the treatment) (Gold et al 1996; Drummond and Jefferson 1996).
Comparator: The choice of comparator (e.g., other medical products, other medical care, no treatment) should be explained (Gold et al. 1996; Husereau et al. 2013).
<!-- page 16 -->Time Horizon: The choice of time horizon should be clearly stated and explained, including its relation to the major and relevant clinical outcomes (e.g., safety and effectiveness) and economic consequences related to the treatment of interest and its comparators (Gold et al. 1996; Husereau et al. 2013).
Outcome Measures: The outcome measure(s) chosen should be described, as should the sources of clinical and/or nonclinical data. For example, clinical outcomes chosen could include patient-reported outcomes (e.g., work productivity, basic activities of daily living) or QALYs. Data sources may include clinical and nonclinical studies or other sources, such as real-world data from administrative databases (e.g., health plan databases), electronic health records, and registries.
Cost Estimates: All of the relevant resource items for measurement and valuation for a treatment pathway in an economic analysis should be identified. Reference should be made to the source of cost data, including the date of the pricing (Husereau et al. 2013). In addition, disclosure of and explanation for any data manipulations and methods (e.g., discount rates, adjustments for inflation, currency conversion) should be included (Husereau et al. 2013).
Assumptions: A listing of all assumptions (clinical and nonclinical) and associated rationales should be made explicit in the explanation of the methodology for the economic analysis (Husereau et al. 2013). Assumptions may include, for example, information related to patient demographics or characteristics, natural disease course, disease management/clinical practice, and cost of clinical events. A list of references for the evidence used to support assumptions made should be provided. Copies of the references should be provided to payors upon request.
- Generalizability
Generalizability refers to the applicability of HCEI obtained in one health care setting or patient population to another. Any factors that may limit the generalizability of the economic analysis should be disclosed (Siegel et al. 1996).
- Limitations
A discussion of the limitations of the economic analysis should be made explicit (Gold et al. 1996). Factors that may affect the interpretability and reliability of an economic analysis include but are not limited to limitations of the study design and methodology. For example, limitations and methodological issues associated with observational studies and indirect treatment comparisons should be described because they may inform conclusions that can be reliably made based on these analyses (Berger et al. 2014; Song et al. 2009).
- Sensitivity Analysis
Uncertainty may arise from data sources, extrapolation, or analytical methods employed in an economic analysis. Therefore, uncertainties that could affect the conclusions in HCEI should be identified, and a sensitivity analysis should be performed. HCEI should include adequate disclosures and rationales regarding the method used for the sensitivity analysis, the variables chosen, and the ranges for those variables (Husereau et al. 2013).
5. Additional Material Information for a Balanced and Complete Presentation
A balanced and complete presentation includes material information. FDA believes the categories of information listed below are generally material to any presentation of HCEI:
Conspicuous and Prominent Statement Describing Material Differences: If HCEI includes material differences from the FDA-approved labeling (e.g., new or increased risks, different dosing/use regimens, different endpoints, more limited/targeted patient populations), including assumptions that vary in certain respects from the information presented in the FDA-approved labeling, "a conspicuous and prominent statement describing any material differences between the health care economic information and the labeling approved for the drug or device" must be presented. For example, if a particular HCEI presentation is based on real-world data where actual patient use of a medical product falls outside of the recommended dosing/use regimen in the FDA-approved labeling, the firm could include a statement such as "The dosing regimen used in this study varies from the dosing regimen in the FDA-approved labeling," in conjunction with the HCEI presentation and in a font size comparable to that used for the other information in the presentation. This example is not intended to suggest this is the only way for this information to be presented. In evaluating whether the statement describing any material differences between the HCEI and the approved labeling is conspicuous and prominent, FDA considers factors such as the location of the statement, the font size and style of the statement text, the contrast between text and background, and the white space between and around text.
Furthermore, firms should not represent that the clinical assumptions that vary from the FDA-approved labeling have been found by FDA to be safe and effective.
Risk Information: HCEI should disclose important risk information associated with the approved use of the medical product and, under section 502(a), must disclose any risk information related to clinical assumptions in economic analyses that is materially different from the FDA-approved labeling (e.g., new risks or different incidence of risk observed in a particular patient subgroup).
FDA-Approved Indication/FDA-Approved Labeling: HCEI should include a statement of the FDA-approved indication of the medical product and be accompanied by the most current FDA-approved labeling.
Disclosure of Omitted Studies or Data Sources: As a general matter, the presentation of HCEI would not be considered balanced and complete if data or information about a medical product
<!-- page 18 -->necessary to understand and contextualize the information is available but was not considered and included in the analysis. This is especially true if the omitted data or information is from rigorous studies (e.g., adequate and well-controlled trials). It is therefore recommended that firms perform a literature search and that their HCEI include an explanation of the methods used in the literature search (e.g., databases or sources used, time period covered, and criteria/keywords used to search the databases and sources and to determine what data or information to include/exclude). If certain studies or data sources were omitted from the analysis, the HCEI should clearly explain the reasons they were not included and how the omission of studies or data sources may change or affect the conclusions.
Financial/Affiliation Biases: HCEI should disclose potential financial or affiliation biases, such as the disseminating firm’s role in funding underlying research or in drafting underlying publications or presentations, or the names of any authors of studies or analyses who received compensation from the firm or who had a significant financial interest in the firm, to the extent reasonably known by the firm at the time of dissemination.
Q8. If HCEI is based on COAs or other health outcome measures, are there any additional considerations of which firms should be aware?
When HCEI includes COAs (e.g., patient-reported outcomes, including work productivity, basic activities of daily living) or other measures of health outcomes (e.g., QALYs), information regarding the validity and reliability of the measures used in assessments of the COA (as determined by experts familiar with evaluating the merits of a particular COA) or the health outcome measure should be included.
Regarding health outcome measures such as QALYs, the following should be considered to facilitate interpretability and comprehensibility of the information: (1) the methods by which the patient’s health status is captured should be disclosed, and the rationale for the health status measures included in the analysis (e.g., physical function, psychological function, social function, impairment, pain) should be provided and (2) the methods for the valuation of health outcomes should be disclosed, and their appropriateness for the patient population and the disease or condition being studied should be explained.
Q9. Is communication of HCEI under section 502(a) considered to be promotional labeling? Do FDA’s requirements for promotional labeling apply to HCEI?
As previously noted, FDA considers communication of HCEI under section 502(a) to be promotional labeling. For prescription drugs, HCEI as described in section 502(a) is subject to FDA’s requirements for submission of promotional materials, including but not limited to the postmarketing requirement under 21 CFR 314.81(b)(3)(i) to submit such materials to FDA at the time of initial publication or dissemination (using Form FDA 2253 (Transmittal of
<!-- page 19 -->Advertisements and Promotional Labeling for Drugs and Biologics for Human Use)) and, for HCEI about drugs submitted for approval under the accelerated approval pathway or about drugs approved based on animal studies, the requirements regarding pre-dissemination submission of promotional materials. All supporting information for HCEI should be referenced and be made available upon request.
Medical device promotional labeling is not subject to a requirement for submission to CDRH on initial publication or dissemination, so HCEI as described in section 502(a) about a medical device is not subject to such a requirement.
Q10. What are the Agency’s policies regarding risk-sharing and other value-based contracts between firms and payors?
This guidance addresses the communication of HCEI to payors, which may include communication of HCEI in the course of discussions between firms and payors related to risk- sharing and other value-based contracts. This guidance, however, is not intended to address the terms of contracts between firms and payors. FDA does not regulate the terms of contracts between firms and payors, and such contracts are not subject to FDA reporting requirements.
B. Communications by Firms to Payors Regarding Unapproved Medical Products and Unapproved Uses of Approved/Cleared Medical Products
Medical product firms may wish to provide certain types of information to payors (as that term, used to collectively refer to payors, formulary committees, and similar entities, is described in Q2) regarding their unapproved medical products and regarding unapproved uses of their approved/cleared medical products. Such information may help payors plan and budget for future coverage and/or reimbursement decisions before FDA approval/clearance of unapproved medical products and may also inform coverage and/or reimbursement decisions for new uses of approved/cleared medical products. This section provides answers to frequently asked questions on this topic.
As noted earlier, section 3630 of the Consolidated Appropriations Act, 2023 added section 481 502(gg) to the FD&C Act, which provides that “no drug or device shall be deemed to be misbranded” under section 502(f)(1) (21 U.S.C. 352(f)(1)) because of certain truthful and not misleading information provided to payors. Section 502(gg) applies to information that “relates to an investigational drug or device or investigational use of a drug or device that is approved, cleared, granted marketing authorization, or licensed under section 505, 510(k), 513(f)(2), or of this Act or section 351 of the Public Health Service Act (as applicable).” We note that this
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section of the guidance applies to truthful and not misleading information about all unapproved medical products and unapproved uses of approved/cleared medical products.
Q11. What are the types of “product information” covered in section 502(gg) of the FD&C Act and in section B of this guidance?
Product information includes:
* Information describing the medical product (such as drug class, device description, and features)
* Information about the indication(s) being investigated, such as information from the clinical study protocol(s) about endpoint(s) being studied and the patient population under investigation (e.g., number of subjects enrolled, subject enrollment criteria, subject demographics)
* Anticipated timeline for possible FDA approval/clearance of the medical product or of the new use
* Medical product pricing information
* Patient utilization projections, such as epidemiological data projection on incidence and prevalence
* Medical product-related programs or services, such as patient support programs
* Factual presentations of results from studies, including clinical studies of medical products or bench tests that describe device performance, “that do not characterize or make conclusions regarding safety or efficacy” of the unapproved medical product or the unapproved use
Below are examples that FDA considers to be appropriate, factual presentations contrasted with presentations that inappropriately characterize or make conclusions regarding safety/effectiveness. The examples illustrate just a few of the many ways firms can appropriately present results from studies:
− A firm intends to submit a marketing application for its medical product for the management of severe pain. An appropriate communication by the firm to payors may include language such as “In an X-week randomized controlled trial comparing PRODUCT to placebo, a statistically significant improvement was observed on the primary endpoint of reduction in mean pain scores from baseline” in conjunction with a graph and/or table summarizing the numerical study results.
<!-- page 21 -->-
By contrast, it would not be appropriate for the firm’s communication to contain language making characterizations or conclusions, such as “PRODUCT allows health care providers to optimize pain relief” or “PRODUCT has been demonstrated to provide potent pain relief.”
-
A firm recently completed a phase 3 trial evaluating its medical product, Drug X, for the treatment of metastatic non-small cell lung cancer and intends to submit a marketing application for this use. An appropriate communication by the firm to payors may include language such as “In a randomized, multi-center trial of Drug X versus [active control] in patients with metastatic non-small cell lung cancer, Drug X met its primary endpoint of improving progression-free survival compared to [active control].”
-
By contrast, it would not be appropriate for the firm’s communication to contain language making characterizations or conclusions, such as “Drug X shows superior efficacy to [active control]” or “We expect Drug X to be the drug of choice for non-small cell lung cancer.”
Q12. What is FDA’s approach with respect to firms that wish to provide “product information” to payors before FDA approval/clearance of an unapproved medical product or an unapproved use of an approved/cleared medical product?
Under section 502(gg) of the FD&C Act, medical products shall not be deemed to be misbranded under section 502(f)(1) through a communication by a firm to a payor about investigational medical products or investigational uses of approved/cleared medical products if such communication is:
(1) The type of product information set forth in section 502(gg)(2), which is discussed in Q11;
(2) Truthful and not misleading;
(3) Presented with the information set forth in section 502(gg)(1)(A), which is discussed in Q13; and
(4) Not presented with the information set forth in section 502(gg)(1)(B), which is discussed in Q14.
While section 502(gg) addresses investigational medical products or investigational uses of medical products, FDA does not intend to object under section 502(f)(1) on the basis of a firm’s communication of product information to payors about unapproved medical products or unapproved uses of approved/cleared medical products, even when such unapproved medical products or uses may not be considered investigational, if the communication of product information is consistent with section 502(gg).
<!-- page 22 -->In addition, FDA does not intend to object under 21 CFR 312.7(a) or 21 CFR 812.7(a) or (d) to communications made in accordance with this guidance or to use such communications, standing alone, as evidence of a new intended use. FDA also does not intend to enforce any applicable postmarketing submission requirements for these materials.
Q13. What information does section 502(gg) of the FD&C Act require and section B of this guidance recommend that “product information” include?
Section 502(gg)(1)(A) of the FD&C Act provides that product information must include:
* A clear statement that the medical product or use is not approved/cleared and that the safety or effectiveness of the medical product or use has not been established
* Information related to the stage of medical product development, such as:
− The status of any study or studies in which a medical product/new use is being investigated;
− How the study or studies relate to the overall medical product development plan; and
− Whether a marketing application or submission for the medical product or new use has been submitted to FDA and when such a submission is planned
* For information that includes factual presentations of results from studies, which shall not be selectively presented (e.g., both positive and negative or null findings are presented), a description of:
− All material aspects of study design, methodology, and results; and
− All material limitations related to the study design, methodology, and results
In addition, where applicable, firms must provide:
* A prominent statement disclosing the indication(s) for which FDA has approved/cleared the medical product, and a copy of the most current FDA-required labeling
Firms must provide updated information to payors if previously communicated information becomes materially outdated as a result of significant changes or as a result of new information
<!-- page 23 -->regarding the medical product (e.g., failure to meet the primary effectiveness endpoint in the pivotal trial) or its review status (e.g., an application is determined to not be ready for approval upon completion of the review cycle, a study is placed on a clinical hold).
As explained earlier, section 502(gg) applies to investigational medical products and investigational uses of approved/cleared medical products, while this guidance applies to unapproved medical products and unapproved uses of approved/cleared medical products. To the extent that there are products to which this guidance applies but section 502(gg) does not, FDA recommends that firms provide the information set forth in section 502(gg)(1)(A).
Q14. What information does section 502(gg) require and section B of this guidance recommend be excluded from “product information”?
Section 502(gg)(1)(B) of the FD&C Act provides that product information must not include information that represents that an unapproved medical product:
* Has been FDA-approved/cleared or
* Has otherwise been determined to be safe or effective for the purpose(s) for which it is being studied
Similarly, product information must not include information that represents:
* That an unapproved use of an approved/cleared medical product is FDA- approved/cleared or
* That the medical product is safe or effective for the use(s) for which it is being studied
To the extent that there are products to which this guidance applies but section 502(gg) does not, FDA recommends that firms do not provide the information set forth in section 502(gg)(1)(B).
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REFERENCES
Berger, ML, BC Martin, D Husereau, K Worley, D Allen, W Yang, C Daniel Mullins, K Kahler, NC Quon, S Devine, J Graham, E Cannon, and W Crown, 2014, A Questionnaire to Assess the Relevance and Credibility of Observational Studies To Inform Health Care Decision Making: An ISPOR-AMCP-NPC Good Practice Task Force Report, Value Health, 17(2):143–156.
Cramer, JA, A Roy, A Burrell, CJ Fairchild, MJ Fuldeore, DA Ollendorf, and PK Wong, 2008, Medication Compliance and Persistence: Terminology and Definitions, Value in Health, 11(1):44–47.
Drummond, MF and TO Jefferson, 1996, Guidelines for Authors and Peer Reviewers of Economic Submissions to the BMJ, BMJ, 313(7052):275–283.
Gold, MR, JE Siegel, LB Russell, and MC Weinstein, editors, 1996, Cost-Effectiveness in Health and Medicine, New York (NY): Oxford University Press, accessed January 29, 2026,
https://academic.oup.com/book/54168
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Husereau, D, M Drummond, S Petrou, C Carswell, D Moher, D Greenberg, F Augustovski, AH Briggs, J Mauskopf, and E Loder, 2013, Consolidated Health Economic Evaluation Reporting Standards (CHEERS) — Explanation and Elaboration: A Report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force, Value in Health, 16(2):231–250.
Siegel, JE, MC Weinstein, LB Russell, and MR Gold, 1996, Recommendations for Reporting Cost-Effectiveness Analyses, Panel on Cost Effectiveness in Health and Medicine, JAMA, 276(16):1339–1341.
Song, F, YK Loke, T Walsh, A-M Glenny, AJ Eastwood, and DG Altman, 2009, Methodological Problems in the Use of Indirect Comparisons for Evaluating Healthcare Interventions: Survey of Published Systemic Reviews, BMJ, 338:b1147.
Footnotes
[1] This guidance has been prepared by the Office of Prescription Drug Promotion in the Office of Medical Policy in the Center for Drug Evaluation and Research in cooperation with the Center for Biologics Evaluation and Research and the Center for Devices and Radiological Health. (page 4)
[2] The term firms refers to medical product manufacturers, packers, and distributors, including representatives of these entities. (page 4)
[3] See Q1 for a definition of HCEI. (page 4)
[4] Each biological product that also meets the definition of a “drug” under the Federal Food, Drug, and Cosmetic Act (FD&C Act) is subject to provisions of the FD&C Act applicable to drugs, except that a biological product licensed under section 351 of the Public Health Service Act (PHS Act) is not required to have an approved new drug application under section 505 of the FD&C Act ( U.S.C. 355). See section 351(j) of the Public Health Service Act (PHS Act) ( U.S.C. 262(j)). In this guidance, the term drugs means human prescription drugs, including those that are licensed as biological products. (page 4)
[5] The term device refers to a medical device intended for human use, including a device that is licensed as a biological product. (page 4)
[6] The terms payors, formulary committees, and other similar entities are discussed in Q2 of this guidance. (page 4)
[7] The term medical products refers to both drugs and devices. (page 4)
[8] In this guidance, the term approved/cleared, as it relates to devices, and similar terms include devices that are legally on the market as a result of premarket approval under section 515 of the FD&C Act; substantial equivalence determination (510(k) clearance) for a premarket notification under section 510(k) of the FD&C Act; De Novo (page 4)
[9] In this guidance, the term unapproved medical products refers to drugs and devices that are not yet approved/cleared by FDA for any use (but that must be approved/cleared to be legally marketed), including medical products for which firms have submitted or plan to submit a new drug application (NDA), a biologics license application (BLA) (including an application submitted under the 351(k) pathway), an abbreviated new drug application (ANDA), a premarket approval application (PMA), a 510(k) submission, a De Novo submission under section 513(f)(2) of the FD&C Act, or a humanitarian device exemption application. (page 5)
[10] The term unapproved uses of approved/cleared medical products and similar terms refer to uses that are not lawfully included as an indication or use in the FDA-required labeling (see footnote 25) of an approved/cleared medical product, including while these uses are under review by the Agency. (page 5)
[11] Ibid. (page 5)
[12] See section 502(a) and 502(gg) of the FD&C Act. (page 6)
[13] The first sentence of section 502(a)(1) of the FD&C Act provides that a “drug or device” is deemed to be misbranded “[i]f its labeling is false or misleading in any particular.” Under longstanding FDA practice and FDA’s statutes, regulations, and case law, “labeling” encompasses more than merely the label of the drug but extends to other written, printed, or graphic matter “accompanying such article” (section 201(m) of the FD&C Act; see also 21 CFR 1.3(a)). According to Kordel v. United States, 335 U.S. 345, 350 (1948), the language “accompanying such article” in the labeling definition in the FD&C Act includes materials that supplement or explain an article; “[n]o physical attachment one to the other is necessary. It is the textual relationship that is significant.” When Congress first amended section 502(a) to include a provision about communication of HCEI, it indicated this provision established that health care economic information “may be included in . . . labeling or advertising submitted to a formulary committee, managed care organization, or similar entity” (see pages 87–88 of the Senate Report on the Food and Drug Administration Modernization and Accountability Act of 1997 (S. 830), S. Rep. No. 105-43, available at <u> (page 6)
[14] The Agency has issued other guidance documents that could apply to firms’ communications to other audiences. For example, FDA issued a draft guidance for firms on responding to unsolicited requests for information about unapproved uses of approved/cleared medical products. See the draft guidance for industry Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices (December 2011) (when final, this guidance will represent FDA’s current thinking on this topic). In addition, FDA issued a guidance regarding certain communications by firms to health care providers of scientific information on unapproved uses of approved/cleared medical products (see the guidance for industry Communications From Firms to Health Care Providers Regarding Scientific Information on Unapproved Uses of Approved/Cleared Medical Products: Questions and Answers (January 2025)). We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web page at <u> (page 8)
[15] See section 502(a) of the FD&C Act, as amended by section 114 of FDAMA; section 3037 of the 21st Century Cures Act; and section 3630 of the Consolidated Appropriations Act, 2023. As used in section III.A of this guidance, section 502(a) refers to the part of that section of the FD&C Act specific to HCEI. (page 8)
[16] Ibid. Section 502(a) further provides that HCEI provided to “a payor, formulary committee, or other similar entity” (payors) that “relates” to an approved indication and is based on “competent and reliable scientific evidence” shall not be considered false or misleading. Those terms are discussed in Q2, Q4, and Q5 of this guidance. (page 8)
[17] Ibid. (page 9)
[18] The term payors refers to entities that are responsible for the financing or reimbursement of costs associated with health care services (e.g., third-party payors, health plan sponsors, State Medicaid programs). (page 9)
[19] The term formulary committees refers to multidisciplinary committees that have the responsibility for the selection of medical products and the management of a formulary. (page 9)
[20] The term health care organizations may include entities such as integrated health care delivery networks, hospitals, and hospital systems. (page 9)
[21] See page 65 of H.R. Rep. No. 105-310. (page 9)
[22] Ibid. (page 9)
[23] See section 502(a) of the FD&C Act. (page 9)
[24] Congress believed that limiting the scope of the audience for HCEI was important because “it will ensure that the information is presented only to parties who have established procedures and skills to interpret the methods and limitations of economic studies. [Section 502(a)] is not intended to permit manufacturers to provide such health care economic information to medical practitioners who are making individual prescribing decisions nor is it intended to permit the provision of such information in the context of medical education.” See page 65 of H.R. Rep. No. 105-310. (page 9)
[25] Section 502(a) applies to HCEI that relates to an "indication approved under section 505, 510(k), 513(f)(2), or 515 of this Act or under section 351(a) of the Public Health Service Act [42 U.S.C. 262(a)]." In this guidance, the term approved indication includes approved/cleared indications. See footnote 8. Additionally, in this guidance, the term FDA-approved labeling includes FDA-required labeling, which includes the labeling approved during the premarket approval process for a device or, for medical products not subject to premarket approval but instead subject to De Novo marketing authorization, premarket notification (510(k)) requirements, Humanitarian Device Exemption pathway, or exempt from premarket review, the labeling that provides adequate directions for use and other information required to appear on the label or in labeling. (page 10)
[26] See section 502(a) of the FD&C Act. (page 10)
[27] Section 502(a)(2)(B) of the FD&C Act also provides that the term HCEI "does not include any analysis that relates only to an indication that is not approved under section 505, 510(k), 513(f)(2), or 515 of this Act or section 351 of the Public Health Service Act. . ." If an analysis is consistent with the recommendations in Q4, FDA would consider it to be within the scope of HCEI as defined in section 502(a). If an analysis is based on data that includes both patients who are within the indicated patient population and patients who are outside of the indicated patient population (e.g., a drug is approved to treat condition X in adults, and a data source used for an analysis only can provide aggregate information for all patients who are using the drug to treat condition X, including pediatric patients), FDA would also consider that to be within the scope of HCEI as defined in section 502(a). On the other hand, if an analysis does not relate at all to an approved indication for a drug, as illustrated by the examples at the end of Q4, FDA would not consider it to be within the scope of HCEI as defined in section 502(a). (page 11)
[28] For more information on surrogate and intermediate clinical endpoints, see the guidance for industry Expedited Programs for Serious Conditions – Drugs and Biologics (May 2014). For devices, see the guidance for industry, tool developers, and FDA staff Qualification of Medical Device Development Tools (July 2023). (page 12)
[29] A COA is any assessment of a patient’s clinical state by the patient or a clinician. There are four types of COA measures: patient-reported outcomes, clinician-reported outcomes, observer-reported outcomes, and performance outcomes. See the guidance for industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (December 2009). (page 12)
[30] The QALY is a measure of the value of a health outcome that is typically scored on a scale from zero (death) to one (perfect or optimal health), integrating the life expectancy and treatment impact on morbidity of the compared interventions that may be used in HCEI. (page 13)
[31] The terms compliance and adherence refer to “the extent to which a patient acts in accordance with the prescribed interval, and dose of a dosing regimen” (Cramer et al. 2008). (page 13)
[32] The term persistence refers to “the duration of time from initiation to discontinuation of therapy” (Cramer et al. 2008). (page 13)
[33] See generally section 502(a)(1) and (a)(2)(B) of the FD&C Act. As a clinical matter, a medical product that is approved only to relieve symptoms of a disease cannot be assumed to prevent, cure, or change the course of the disease; therefore, assumptions about the health care economic consequences of use of such a medical product for preventing, curing, or changing the course of the disease would not be considered to relate to the medical product’s approved indication. See also page 66 of H.R. Rep. No. 105-310 for additional discussion. (page 13)
[34] Regarding study design limitations, firms should disclose whether the study lacked randomization, blinding, or a control group; lacked assay sensitivity; failed to include pre-specified endpoints; failed to include endpoints that are valid and reliable measures of the outcomes of interest; failed to identify dosing, patient population, patient dropouts, or selection and timing of endpoints; failed to meet the primary endpoint; etc. (page 16)
[35] See section 502(a). (page 17)
[40] See footnotes 9 and 10. (page 20)
[41] See section 502(gg)(2) of the FD&C Act. Generally, for devices, FDA interprets “efficacy” to mean “effectiveness” consistent with other provisions in the FD&C Act. (page 20)