IC recommended in FDA guidance

Drug and Device Manufacturer
Communications With Payors,
Formulary Committees,
and Similar Entities
Questions and Answers
Guidance for Industry
and Review Staff

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)
Office of the Commissioner (OC)

June 2018
Procedural

OMB Control No. 0910-0857
Expiration Date: 08/31/2024
(Note: OMB control number and expiration date added 09/28/2021)
See additional PRA statement in section IV of this guidance.

Drug and Device Manufacturer
Communications With Payors, Formulary
Committees, and Similar Entities
Questions and Answers
Guidance for Industry and Review Staff
Additional copies are available from:
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and/or
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and/or
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Food and Drug Administration
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and/or
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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)
Office of the Commissioner (OC)
June 2018
Procedural

Contains Nonbinding Recommendations
TABLE OF CONTENTS

I.

INTRODUCTION............................................................................................................. 1

II.

BACKGROUND ............................................................................................................... 2

III.

QUESTIONS AND ANSWERS ....................................................................................... 4

A.

Communications of HCEI by Firms to Payors Regarding Approved Drugs ........................... 4

B.

Communications of HCEI by Firms to Payors Regarding Approved or Cleared Medical

Devices ................................................................................................................................................... 17
C.

Communications by Firms to Payors Regarding Unapproved Products and Unapproved

Uses of Approved/Cleared Products ................................................................................................... 18

IV.

PAPERWORK REDUCTION ACT OF 1995.............................................................. 22

Contains Nonbinding Recommendations

Drug and Device Manufacturer Communications With Payors,
Formulary Committees, and Similar Entities
Questions and Answers
Guidance for Industry and Review Staff 1
This guidance represents 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 office responsible for this guidance as listed on the
title page.

I.

INTRODUCTION

This guidance provides answers to common questions regarding firms’ 2 communication of health
care economic information (HCEI) 3 regarding their prescription drugs 4 and medical devices 5 to
payors, formulary committees, or other similar entities 6 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 7 that are not yet approved or cleared for any use and dissemination to payors of
information about unapproved uses of approved/cleared medical products.
1

This guidance has been prepared by the Office of Prescription Drug Promotion in the Center for Drug Evaluation
and Research in cooperation with the Center for Biologics Evaluation and Research, the Center for Devices and
Radiological Health, and the Office of the Commissioner at the Food and Drug Administration.

2

The term “firms” refers to medical product manufacturers, packers, and distributors, including representatives of
these entities.

3

See Q.A.1/A.A.1 for a definition of HCEI.

4

Each biological product that also meets the definition of “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 (21 U.S.C. 355). See section 351(j) of the PHS Act (42 U.S.C.
262(j)). For the purposes of this guidance, the term “drugs” means human prescription drugs, including those that
are licensed as biological products.
5

The term “device” refers to a medical device intended for human use, including a device that is licensed as a
biological product.

6

The terms “payors, formulary committees, or other similar entities” are discussed in Q.A.2/A.A.2 of this guidance.

7

The term “medical products” refers to both drugs and devices.

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The questions and answers are grouped in the following categories:
•

Communications of HCEI to payors regarding approved drugs;

•

Communications of HCEI to payors regarding approved/cleared devices; 8

•

Communications to payors about unapproved drugs/devices (unapproved products 9); 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
the word should in Agency guidances means that something is suggested or recommended, but
not required.

II.

BACKGROUND

A number of FDA’s statutory and regulatory provisions potentially impact firms’
communications with payors. 10 This guidance provides FDA’s thinking on frequently asked
questions regarding such communications in order to provide clarity to firms and payors.
8

As used in this guidance, the term “approved/cleared device,” and similar terms, includes devices that are legally
on the market as a result of premarket approval, 510(k) clearance, De Novo marketing authorization, a humanitarian
device exemption (HDE) approval, or an exemption from premarket notification.

9

As used in this guidance, the term “unapproved products” refers to drugs and devices that are not yet
approved/cleared by FDA for any use (but which must be approved/cleared to be legally marketed), including
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 (21 U.S.C. 360c(f)(2)), or a HDE application.

10

For example, section 502(a) of the FD&C Act, (section 502(a)), as amended by section 114 of the Food and Drug
Administration Modernization Act of 1997 (FDAMA) (Public Law 105-115) and section 3037 of the 21st Century
Cures Act (Public Law 114-255), includes the following provision regarding communication of HCEI to payors
about approved drugs:
“Health care economic information 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 for coverage or reimbursement, shall not be considered to be
false or misleading under this paragraph if the health care economic information relates to an
indication approved under section 505 or under section 351(a) of the Public Health Service Act [42
U.S.C. 262(a)] for such drug, is based on competent and reliable scientific evidence, and includes,
where applicable, a conspicuous and prominent statement describing any material differences between
the health care economic information and the labeling approved for the drug under section 505 or
under section 351 of the Public Health Service Act. The requirements set forth in section 505(a) or in
subsections (a) and (k) of section 351 of the Public Health Service Act shall not apply to health care
economic information provided to such a payor, committee or entity in accordance with this
paragraph. Information that is relevant to the substantiation of the health care economic information

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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 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
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.
Because coverage and reimbursement decisions by payors impact many patients, FDA believes it
is critical that information provided by firms to payors about their medical products be truthful
and non-misleading and that appropriate background and contextual information be provided to
enable payors to make informed decisions. 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 non-misleading. Specifically, section III.A provides FDA’s
thinking on frequently asked questions regarding communication of HCEI to payors about
approved prescription drugs under section 502(a) of the FD&C Act (21 U.S.C. 352(a)). Section
III.B provides FDA’s thinking on frequently asked questions regarding communication of HCEI
to payors about approved/cleared devices. As noted in section III.B, although the language in
section 502(a) addressing HCEI applies only to drugs, the general requirement in section 502(a)
that labeling not be false or misleading applies to devices as well as to drugs. FDA considers
firms’ communications of HCEI to payors that otherwise meet the definition in section 201(m) of
the FD&C Act (21 U.S.C. 321(m)) to be labeling. 11 Thus, FDA believes the recommendations
presented pursuant to this paragraph shall be made available to the Secretary [of Health and Human
Services] upon request . . . For purposes of this paragraph, the term ‘health care economic
information’ means 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. Such analysis may be
comparative to the use of another drug, to another health care intervention, or to no intervention….
Such term does not include any analysis that relates only to an indication that is not approved under
section 505 or under section 351 of the Public Health Service Act for such drug.”
11

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
statute, 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 https://www.congress.gov/congressional-report/105th-congress/senate-report/43/1), and that under
“FDA’s current postmarketing reporting regulations, health care economic information as defined in this section

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provided in section III.A are generally applicable to firms’ communication of HCEI to payors
about devices as well, and can help ensure these communications are not false or misleading.
Payors have also indicated that due, in part, to their need to, in some situations, 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 about unapproved uses of
approved/cleared medical products. For the reasons described previously, it is critical that
information provided by firms about their unapproved products and about unapproved uses of
approved/cleared products be truthful and non-misleading. Section III.C provides FDA’s
thinking on frequently asked questions regarding communications to payors about unapproved
products and about unapproved uses of approved/cleared products.

III.

QUESTIONS AND ANSWERS
A.

Communications of HCEI by Firms to Payors Regarding Approved Drugs

Q.A.1.

What is HCEI, and how can it be presented?

A.A.1.

HCEI is defined in section 502(a) 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.
Such analysis may be comparative to the use of another drug, to another health
care intervention, or to no intervention.” 12 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. 13 HCEI may include

must be submitted to the FDA at the time it is initially provided to a formulary committee or other similar entity”
(see page 67 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
https://www.congress.gov/congressional-report/105/house-report/310). The referenced postmarketing reporting
requirements apply to promotional labeling (as well as to advertisements) (see 21 CFR 314.81(b)(3)(i)). Since
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 Q.A.9/A.A.9.
The Agency similarly considers communications of HCEI about devices to be promotional labeling.
12

See section 502(a), as amended by section 114 of FDAMA and section 3037 of the 21st Century Cures Act. As
used in this guidance, the term “section 502(a)” refers to the part of that section specific to HCEI.
13

See footnote 12. 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 Q.A.2/A.A.2, Q.A.4/A.A.4, and
Q.A.5/A.A.5 of this guidance.

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comparative analyses of the economic consequences of a drug’s clinical outcomes
to alternative options (including the use of another drug) 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.
Q.A.2.

What is the appropriate scope of the audience for the communication of HCEI
about approved drugs under section 502(a)?

A.A.2.

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 for coverage or reimbursement.” 14
This audience includes public and private sector payors, 15 formulary committees 16
(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, 17 review scientific and/or technology assessments to make drug or
device selection or acquisition, formulary management, and/or coverage and
reimbursement decisions on a population basis. 18
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 decisionmaking process. 19,20 Expertise in this area is critical to understand and evaluate
health care economic analyses and their limitations.

14

See footnote 13.

15

The term “payors” refers to entities who 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).
16

The term “formulary committees” refers to multidisciplinary committees that have the responsibility for the
selection of drugs and the management of a drug formulary.
17
The term “health care organizations” may include entities such as integrated health care delivery networks,
hospitals, and hospital systems.
18

See page 65 of H.R. Rep. No. 105-310.

19

See footnote 18.

20

See section 502(a).

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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. 21 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 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
professional 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 drugs for coverage or reimbursement for a payor, formulary
committee, or similar entity.
Q.A.3.

How does FDA intend to implement this guidance for HCEI disseminated in
accordance with section 502(a)?

A.A.3.

If a firm disseminates to an appropriate audience HCEI that is the type of
information within the scope of 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 Q.A.7/A.A.7 and Q.A.8/A.A.8
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 FDAapproved 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,” 22
as discussed in Q.A.7/A.A.7.
In addition, FDA does not intend to use HCEI that is disseminated consistent with
this guidance as evidence of a new intended use.

21
Congress believed that limiting the scope of the audience for HCEI is 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.
22

See section 502(a).

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Q.A.4.

Section 502(a) provides that HCEI shall not be considered false or misleading
if, among other things, it “relates to an [approved] indication.” 23 What types of
information does FDA consider to relate to an approved indication?

A.A.4.

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 drug 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 drug, 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.

Examples of HCEI Analyses That Relate to an Approved Indication
Example
Description
Where the approved indication for a drug does not
Duration of Treatment
limit the duration of use, HCEI analyses may
incorporate information about the long-term use of
the drug 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 drug 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

23

HCEI analyses may be based on use of the drug 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

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 or under section 351 of the Public Health Service
Act. . .” If an analysis is consistent with the recommendations in Q.A.4/A.A.4, 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 Q.A.4/A.A.4, FDA
would not consider it to be within the scope of HCEI as defined in this section.

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Example

Burden of Illness

Dosing/Use Regimen

Patient Subgroups

Length of Hospital Stay
Surrogate or Intermediate
Endpoints

Description
other setting, or results of clinical trials conducted
in a hospital center could be extrapolated to an
ambulatory care setting).

HCEI analyses may be derived from studies of the
burden of a disease for which the drug is
indicated, including economic consequences 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).

HCEI analyses may be based on data or studies of
approved dosage forms and strengths of a drug 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).
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 drug.
HCEI analyses may be derived from studies of
treatment impacts on length of hospital stay.

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
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Example
Clinical Outcome
Assessments (COAs) 25 or
Other Health Outcome
Measures (e.g., QualityAdjusted Life Year
(QALY)) 26

Compliance/Adherence 27

Persistence 28

Comparisons

Description
reasonably likely to predict clinical benefit. 24

HCEI analyses may be derived from studies
involving the approved indication of a drug that
assess COAs (e.g., patient-reported outcomes
(PROs), such as work productivity, basic activities
of daily living) or other health outcome measures
(e.g., QALY) 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).
HCEI analyses may be derived from studies
assessing patient compliance/adherence with a
drug for its approved indication.
HCEI analyses may be based on data estimating
patient persistence on a drug for its approved
indication (e.g., estimates based on drug
utilization data from a health plan database).

HCEI analyses may be derived from studies
comparing the safety or effectiveness of a drug for
its approved indication to another drug or

24

For more information on surrogate and intermediate clinical endpoints, see FDA’s guidance for industry
Expedited Programs for Serious Conditions – Drugs and Biologics, and, for devices, see FDA’s guidance for
industry, tool developers, and Food and Drug Administration staff Qualification of Medical Device Development
Tools. We update guidances periodically. For the most recent version of a guidance, check the FDA guidance web
page at http://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
25
A COA is any assessment of a patient’s clinical state by the patient or a clinician. There are four types of COA
measures (i.e., patient-reported outcomes, clinician-reported outcomes, observer-reported outcomes, and
performance outcomes). See FDA’s guidance for industry Patient-Reported Outcome Measures: Use in Medical
Product Development to Support Labeling Claims.
26

A QALY is a measure of the value of a health outcome that is typically scored on a scale from zero (corresponds
to death) to one (corresponds to perfect or optimal health), integrating the life expectancy and treatment impact on
morbidity of the compared interventions that may be used in HCEI.
27

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.” See Cramer JA, Roy A, Burrell A, et al., Medication
Compliance and Persistence: Terminology and Definitions, Value in Health, 2008;11(1):44-47.
28

The term “persistence” refers to “the duration of time from initiation to discontinuation of therapy.” See footnote
27.

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Example

Description
intervention or to no treatment.

The following are examples of HCEI analyses that are not considered to relate to an
approved indication:
•

If a drug is approved only to relieve the symptoms of a disease, HCEI analyses
regarding use of the drug to prevent, cure, or mitigate/change the course of the
disease would not be considered related to the drug’s approved indication. 29
Thus, for example, if an analysis for a drug indicated for the management of pain
in cancer patients discussed the effect of the drug on delaying the progression of
cancer or on 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 drug. For example, if a drug is approved only for use in 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
drug.

Q.A.5.

What evidentiary support should firms have for their HCEI under section
502(a)?

A.A.5.

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, appropriate for the information
being conveyed, that yield accurate and 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, International Society for Pharmacoeconomic and Outcomes Research
(ISPOR), International Society for Pharmacoepidemiology (ISPE), PatientCentered Outcomes Research Institute (PCORI), and 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

29

See generally section 502(a)(1) and (a)(2)(B) of the FD&C Act. As a clinical matter, a drug 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 product for preventing, curing, or
changing the course of the disease would not be considered to relate to the product’s approved indication. See also
page 66 of H.R. Rep. No. 105-310 for additional discussion.

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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 Q.A.7/A.A.7 and Q.A.8/A.A.8 of this guidance, including study
design and methodology, generalizability, limitations, sensitivity analyses, and
information relevant to providing a balanced and complete presentation.
Q.A.6.

Does the CARSE standard apply only to the economic components of HCEI, or
does it also apply to the other components?

A.A.6.

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 drug’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 Q.A.4/A.A.4, such
information must also relate to an approved indication in order to fall within the
provisions of section 502(a) regarding HCEI.

Q.A.7.

What information should firms include when disseminating HCEI?

A.A.7.

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 (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) is provided, as further 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 include 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.

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Contains Nonbinding Recommendations
1.

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. 30
Modeling: The type of modeling technique should be disclosed, with an explanation of the
model choice, its scope, and its key variables/parameters. 31 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. 32,33
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). 34,35
Comparator: The choice of comparator (e.g., other drugs, other medical care, no treatment)
should be explained. 36,37
30
Drummond MF, Jefferson TO, Guidelines for Authors and Peer Reviewers of Economic Submissions to the BMJ,
BMJ, 1996;313:(7052):275-283.
31

Husereau D, Drummond M, Petrou S, et al., 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, 2013;16:231-250.
32

Gold MR, Siegel JE, Russell LB, et. al., editors, Cost-Effectiveness in Health and Medicine, New York, NY:
Oxford University Press, 1996.
33

See footnote 31.

34

See footnote 32.

35

See footnote 30.

36

See footnote 32.

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Contains Nonbinding Recommendations

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. 38,39
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 PROs (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 (EHRs),
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. 40 In addition, disclosure of and
explanation for any data manipulations and methods (e.g., discount rates, adjustments for
inflation, currency conversion) should be included. 41
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. 42 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.
2.

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. 43

37

See footnote 31.

38

See footnote 32.

39

See footnote 31.

40

See footnote 31.

41

See footnote 31.

42

See footnote 31.

43

Siegel JE, Weinstein MC, Russell LB, et al., Recommendations for Reporting Cost-Effectiveness Analyses, Panel
on Cost Effectiveness in Health and Medicine, JAMA, 1996;276(16):1339-1341.

13

Contains Nonbinding Recommendations

3.

Limitations

A discussion of the limitations of the economic analysis should be made explicit. 44 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. 45 For example, limitations and
methodological issues associated with observational studies 46 and indirect treatment
comparisons 47 should be described as they may inform conclusions that can be reliably made
based on these analyses.
4.

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. 48
5.

Additional Material Information for a Balanced and Complete Presentation

A balanced and complete presentation includes material information such as the following. 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

44

See footnote 32.

45

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 drop
outs, selection and timing of endpoints; failed to meet the primary endpoint; etc.
46
Berger ML, Martin BC, Husereau D, et al., 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, 2014;17(2):143-156.
47

Song F, Loke YK, Walsh T, et al., Methodological Problems in the Use of Indirect Comparisons for Evaluating
Healthcare Interventions: Survey of Published Systemic Reviews, BMJ, 2009;338:b1147.
48

See footnote 31.

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Contains Nonbinding Recommendations
approved for the drug” 49 must be presented. For example, if a particular HCEI presentation
is based on real-world data where actual patient use of the drug 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 a statement 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 misleadingly represent that the clinical assumptions that vary
from the FDA-approved labeling have been found by FDA to be safe and effective.
FDA-Approved Indication/FDA-Approved Labeling: HCEI should include a statement of
the FDA-approved indication of the drug and be accompanied by the most current FDAapproved 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 product
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.
Risk Information: HCEI should disclose important risk information associated with the
approved use of the drug and, under section 502(a), must disclose any additional risk
information related to clinical assumptions in economic analyses that vary from the FDAapproved labeling (e.g., risks observed in a particular patient subgroup).
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.

49

See section 502(a).

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Contains Nonbinding Recommendations
Q.A.8.

If HCEI is based on COAs or other health outcome measures, are there any
additional considerations of which firms should be aware?

A.A.8.

When HCEI includes COAs (e.g., PROs, 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) 50 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.

Q.A.9.

Is HCEI for prescription drugs disseminated in accordance with section 502(a)
considered to be promotion? Do FDA’s requirements for promotional
materials apply to HCEI?

A.A.9.

HCEI disseminated in accordance with section 502(a) is promotion 51 and,
therefore, is subject to FDA’s requirements for submission of promotional
materials. These include, but are not limited to, the postmarketing requirement at
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
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, 52 the
requirements regarding pre-dissemination submission of promotional materials.
All supporting information for HCEI should be referenced and be made available
upon request. 53

50

For further guidance regarding characteristics of valid and reliable assessments of COAs, please see FDA’s
guidance for industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support
Labeling Claims.
51

See footnote 11.

52

See 21 CFR 314.550, 314.640, 601.45, and 601.94.

53

In addition, under section 502(a), if FDA requests submission of information that is relevant to the substantiation
of HCEI, firms are required to provide FDA with such information, which may include the primary data and
analysis methods used to support the HCEI.

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Contains Nonbinding Recommendations
Q.A.10.

What are the Agency’s policies regarding risk-sharing and other value-based
contracts between firms and payors?

A.A.10.

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 of HCEI by Firms to Payors Regarding Approved or
Cleared Medical Devices

Q.B.1.

To what extent do the recommendations described in section III.A of this
guidance apply to devices?

A.B.1.

Following issuance of the draft of this guidance, several commenters suggested
that the recommendations describing appropriate communication of HCEI by
firms to payors about approved drugs in section III.A of the guidance could also
be applied to devices. 54 Although the language in section 502(a) addressing
HCEI applies to drugs, not devices, FDA believes the recommendations provided
in section III.A are generally applicable to device firms’ communication of HCEI
to payors as well. Although section III.A refers to “drugs,” “approved
indications/approved uses,” and “FDA-approved labeling,” the recommendations
for “drugs” generally apply to “devices” and “approved/cleared indications/uses”
and “FDA-required labeling” 55 as well. Although the HCEI language in section
502(a) is specific to drugs, the requirement in section 502(a) that information not
be false or misleading applies to both drugs and devices, and the
recommendations provided in section III.A can help ensure that device firms’
communication of HCEI to payors is not false or misleading. We note, however,
that device firms are not subject to the same postmarketing reporting requirements
to submit promotional materials as described in Q.A.9, so the information
provided in A.A.9 regarding submission of promotional materials does not apply
to devices.

54
In the notice of availability of the draft version of this guidance that published in the Federal Register of
January 19, 2017 (82 FR 6568), we specifically requested comments from interested parties on this issue (82 FR at
6568 at 6571).
55

The term “FDA-required labeling” includes the labeling approved during the premarket approval process for a
device, or, for products not subject to premarket approval but instead subject to De Novo marketing authorization,
premarket notification (510(k)) requirements, 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.

17

Contains Nonbinding Recommendations
As stated in Q.A.3/A.A.3, if a device firm disseminates HCEI that complies with
the recommendations in section III.A, FDA does not intend to consider such
information false or misleading or evidence of a new intended use.
C.

Communications by Firms to Payors Regarding Unapproved Products and
Unapproved Uses of Approved/Cleared Products 56

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 Q.A.2/A.A.2) regarding their unapproved products and regarding unapproved
uses of their approved/cleared/licensed products. Such information may help payors plan
and budget for future coverage and/or reimbursement decisions prior to FDA approval,
clearance, or licensure of unapproved products and may also inform coverage and/or
reimbursement decisions for new uses of approved/cleared/licensed products. This section
provides answers to frequently asked questions on this topic.
Q.C.1.

What are the types of information covered in this section of the guidance, and
what is FDA’s approach with respect to firms that wish to provide such
information prior to FDA approval, clearance, or licensure of an unapproved
product or to provide such information about an unapproved use of an
approved/cleared/licensed product?

A.C.1.

When the following types of information about unapproved products (as defined
in this guidance) or unapproved uses of approved/cleared/licensed products
provided by firms to payors are unbiased, factual, accurate, and non-misleading,
and are presented with information discussed in Q.C.2/A.C.2, FDA does not
intend to object under 21 CFR 312.7(a) or 21 CFR 812.7(a) to such
communications, nor to use such communications as evidence of a new intended
use. 57 FDA also does not intend to enforce any applicable postmarketing
submission requirements for these materials. 58
•

Product information (e.g., drug class, device description and features).

56

The draft version of this guidance contained recommendations for communications by firms to payors regarding
drugs and devices that are not yet approved or cleared for any use (referred to in the draft guidance as investigational
drugs and devices). FDA received many comments requesting that the Agency also provide recommendations for
communications by firms to payors regarding unapproved uses of approved/cleared products. After consideration of
these comments, FDA has included recommendations for such communications in this guidance.

57

With respect to unsolicited requests by payors to firms, this guidance is not intended to supersede FDA’s draft
guidance for industry Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and
Medical Devices. When final, this guidance will represent FDA’s current thinking on this topic.
58

For example, see 21 CFR 314.81(b)(3)(i), 314.550, 314.640, 601.45, or 601.94.

18

Contains Nonbinding Recommendations
•

Information about the indication(s) sought, 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/licensure of the
product or of the new use.

•

Product pricing information.

•

Patient utilization projections (e.g., epidemiological data projection on
incidence and prevalence).

•

Product-related programs or services (e.g., patient support programs).

•

Factual presentations of results from studies, including clinical studies of
drugs or devices or bench tests that describe device performance (i.e., no
characterizations or conclusions should be made regarding the safety or
effectiveness of the unapproved product or the unapproved use). Below are
examples of 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. Firms should also refer
to Q.C.2/A.C.2 for recommendations with respect to information they should
provide when communicating to payors about unapproved products or about
unapproved uses of approved/cleared/licensed products:
−

A firm intends to submit a marketing application for its product for the
management of severe pain. An appropriate communication by the firm
to payors may include language such as “In a 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.


−

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 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

19

Contains Nonbinding Recommendations
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.”

Q.C.2.

What other information should firms provide to payors when communicating
information about their unapproved products or about unapproved uses of
approved/cleared/licensed products?

A.C.2.

FDA recommends that firms provide the following information to payors when
communicating information about unapproved products or about unapproved uses
of approved/cleared/licensed products:
•

A clear statement that the product or use is not approved/cleared/licensed, and
that the safety or effectiveness of the product or use has not been established;

•

Information related to the stage of product development (e.g., the status of any
study(ies) in which a product/new use is being investigated and how it relates
to the overall product development plan, whether a marketing application for
the product or new use has been submitted to FDA or when such a submission
is planned); and

•

For communications that include factual presentations of results from studies,
FDA recommends that firms describe material aspects of study design and
methodology and also disclose material limitations related to the study design,
methodology, and results. Firms should also ensure that results are not
selectively presented (e.g., both positive and negative or null findings should
be presented).

In addition, for communications to payors about unapproved uses of
approved/cleared/licensed products, firms should provide:
•

A prominent statement disclosing the indication(s) for which FDA has
approved, cleared, or licensed the product and a copy of the most current
FDA-required labeling.

FDA also suggests that firms provide follow-up information to payors if
previously communicated information becomes materially outdated as a result of
significant changes or as a result of new information regarding the 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).

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Contains Nonbinding Recommendations
Q.C.3.

What types of information would be considered inappropriate to communicate
to payors about unapproved products or about unapproved uses of
approved/cleared/licensed products?

A.C.3.

Communications between firms and payors that represent that an unapproved
product is FDA-approved/cleared/licensed, or has otherwise been determined safe
or effective for the purpose(s) for which it is being studied would not be
appropriate. Similarly, communications between firms and payors that represent
that an unapproved use of an approved/cleared/licensed product is FDAapproved/cleared/licensed or that the product is safe or effective for the use(s) for
which it is being studied would not be appropriate.

Q.C.4.

What additional considerations apply to communications to payors about
unapproved products and about unapproved uses of approved/cleared/licensed
products?

A.C.4.

Firms’ communications regarding unapproved products and unapproved uses of
approved/cleared/licensed 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 firm communications regarding unapproved products or unapproved uses of
approved/cleared/licensed medical products may potentially undermine
substantial government interests related to health and safety. These interests
include motivating the development of robust scientific data on safety and
efficacy; maintaining the premarket review process for safety and efficacy 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; and preventing the diversion of health care resources
toward ineffective treatments.
FDA recognizes that there can be, in certain instances, tension between the public
health interests directly advanced by the premarket review requirements and other
important interests. For example, as discussed in section II of this guidance, FDA
recognizes that payors, in some situations, 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. As a result, FDA recognizes the value of payors
receiving unbiased, factual, accurate, and non-misleading information of the type
described in Q.C.1/A.C.1 about unapproved products and unapproved uses of
approved/cleared/licensed medical products in order to inform their decisionmaking.
FDA believes that the categories of information described in Q.C.1/A.C.1 are, on
the one hand, broad enough to encompass the information that payors may need to

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Contains Nonbinding Recommendations
make informed coverage and reimbursement decisions and, on the other hand,
limited enough to maintain appropriate incentives for firms to conduct robust
studies to evaluate the safety and efficacy of unapproved products and
unapproved uses of approved/cleared/licensed medical products. In addition, if
firms follow the recommendations in Q.C.1/A.C.1 and provide unbiased, factual,
accurate, and non-misleading information, FDA believes that the risk that payors
will be misled is relatively low. Payors are a sophisticated audience with
established procedures to carefully consider the full range of relevant evidence
about new uses of medical products. Payors possess financial resources and
motivation to closely scrutinize information from firms. 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.
Thus, FDA believes the recommendations provided in this section of the guidance
appropriately balance the competing interests described above for firms’
communications with payor audiences about unapproved products and
unapproved uses of approved/cleared/licensed products. Firms’ communications
to other audiences about unapproved products or unapproved uses of
approved/cleared/licensed products could raise additional or different
considerations and are beyond the scope of this guidance. 59

IV.

PAPERWORK REDUCTION ACT OF 1995

This guidance contains information collection provisions that are subject to review by the Office
of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C.
3501-3520). Specifically, the guidance contains recommendations for information that should be
included when HCEI about approved prescription drugs and about approved or cleared devices is
disseminated to payors. FDA also recommends that certain information be included in firms’
communications with payors about unapproved products and about unapproved uses of
approved/cleared products.
FDA estimates that it will take firms approximately 20 hours to compile and draft the
information that this guidance recommends should be included when disseminating HCEI for
59

The Agency has issued other guidance documents that could apply to firms’ communications to other audiences.
For example, FDA has issued a draft guidance for industry describing its thinking on how firms can respond to
unsolicited requests for unapproved use information related to their FDA-approved prescription drugs and FDAapproved or cleared medical devices. See FDA’s draft guidance for industry Responding to Unsolicited Requests for
Off-Label Information About Prescription Drugs and Medical Devices. In addition, FDA has provided separate
guidances describing recommended practices for the dissemination by firms of scientific and medical publications
discussing unapproved uses of approved drugs or approved or cleared medical devices. See FDA’s guidance for
industry 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,
and FDA’s revised draft guidance Distributing Scientific and Medical Publications on Unapproved New Uses –
Recommended Practices.

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Contains Nonbinding Recommendations
approved prescription drugs and approved/cleared devices. FDA estimates it will take firms
approximately 30 minutes to compile and draft the information that this guidance recommends
should be provided with communications to payors about unapproved products or unapproved
uses of approved/cleared products, and that it will take about 2 hours for firms to compile and
provide communications of follow-up information regarding previously communicated
information to payors about their unapproved products or unapproved uses of approved/cleared
products. Send comments regarding this burden estimate or suggestions for reducing this burden
to:
FDA PRA Staff
Office of Operations
Food and Drug Administration
Three White Flint North
11601 Landsdown Street, 10A-12M
North Bethesda, MD 20852
This guidance also refers to previously approved collections of information found in FDA
regulations. The collections of information in 21 CFR 314.81(b)(3)(i) (Form FDA 2253) have
been approved under OMB control number 0910-0001.
An Agency may not conduct or sponsor, and a person is not required to respond to, a collection
of information unless it displays a currently valid OMB control number. The OMB control
number for this information collection is 0910-0857 (expires 08/31/2024 (Note: OMB control
number and expiration date added 09/28/2021)).

23