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: 
 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
and/or 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm    
and/or 
Office of the Center Director 
Center for Devices and Radiological Health 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 66, Room 5431 
Silver Spring, MD 20993-0002 
Email: CDRH-Guidance@fda.hhs.gov 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.htm 
and/or 
Office of Policy 
Office of the Commissioner 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 32, Room 4232 
Silver Spring, MD  20993-0002 
Phone: 301-796-4830 
 
 
 
 
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 Staff1 
 
 
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 firms2 communication of health 
care economic information (HCEI)3 regarding their prescription drugs4 and medical devices5 to 
payors, formulary committees, or other similar entities6 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 
products7 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. 
 
  1  Contains Nonbinding Recommendations 
 
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 products9); and 
about unapproved uses of approved/cleared medical products.  
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys 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 FDAs statutory and regulatory provisions potentially impact firms 
communications with payors.10  This guidance provides FDAs 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 
 
  2  Contains Nonbinding Recommendations 
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 FDAs 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 FDAs 
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 FDAs 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 FDAs 
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 
FDAs current postmarketing reporting regulations, health care economic information as defined in this section 
 
  3  Contains Nonbinding Recommendations 
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 FDAs 
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, FDAs 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.  
 
  4  Contains Nonbinding Recommendations 
comparative analyses of the economic consequences of a drugs 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 committees16 
(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 decision-
making 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). 
 
  5  Contains Nonbinding Recommendations 
 
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 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,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). 
 
  6  Contains Nonbinding Recommendations 
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 
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cceormtapirneh reensspiveec tosr f rreosmtr,i cintifvoer.m  ation presented in the FDA-approved labeling.  
Examples of HCEI Analyses That Relate to an Approved Indication  
E  xample  Description 
Duration of Treatment  Where the approved indication for a drug does not 
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 
 
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 
23 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. 
 
  7  Contains Nonbinding Recommendations 
Example  Description 
other setting, or results of clinical trials conducted 
in a hospital center could be extrapolated to an 
Burden of Illness  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 
Dosing/Use Regimen  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 
Patient Subgroups  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 
Length of Hospital Stay  formed the basis for approval of the drug. 
 
HCEI analyses may be derived from studies of 
Surrogate or Intermediate  treatment impacts on length of hospital stay. 
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 
  8  Contains Nonbinding Recommendations 
Example  Description 
24
Clinical Outcome   reasonably likely to predict clinical benefit.    
Assessments (COAs)25 or   
Other Health Outcome  HCEI analyses may be derived from studies 
Measures (e.g., Quality- involving the approved indication of a drug that 
Adjusted Life Year  assess COAs (e.g., patient-reported outcomes 
(QALY))26  (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 
Compliance/Adherence27  particular COA or other health outcome measure). 
 
HCEI analyses may be derived from studies 
assessing patient compliance/adherence with a 
Persistence28  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 
Comparisons   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 FDAs guidance for industry 
Expedited Programs for Serious Conditions  Drugs and Biologics, and, for devices, see FDAs 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 patients 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 FDAs 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. 
   
  9  Contains Nonbinding Recommendations 
Example  Description 
  intervention or to no treatment. 
The following are examples of HC EI 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 drugs 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), Patient-
Centered 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 products approved indication.  See also 
page 66 of H.R. Rep. No. 105-310 for additional discussion. 
 
  10  Contains Nonbinding Recommendations 
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 drugs 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.   
 
  11  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. 
 
  12  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 studies46 and indirect treatment 
comparisons47 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. 
 
  14  Contains Nonbinding Recommendations 
approved for the drug49 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 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 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 FDA-
approved 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 firms 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).   
 
  15  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 patients 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 FDAs requirements for promotional 
materials apply to HCEI?  
 
A.A.9.  HCEI disseminated in accordance with section 502(a) is promotion51 and, 
therefore, is subject to FDAs 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 FDAs 
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.   
 
  16  Contains Nonbinding Recommendations 
Q.A.10.  What are the Agencys 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 labeling55 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 Products56 
 
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 FDAs 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 FDAs draft 
guidance for industry Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and 
Medical Devices.  When final, this guidance will represent FDAs 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 firms 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 firms 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).   
 
  20  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 FDA-
approved/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.  FDAs 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 decision-
making.   
 
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 
  21  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 FDA-
approved or cleared medical devices.  See FDAs 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 FDAs 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 FDAs revised draft guidance Distributing Scientific and Medical Publications on Unapproved New Uses  
Recommended Practices.   
  22  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)). 
 
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