The recent enactment of the 21st Century Cures Act has profound immediate and long-term implications for development and communication of HEOR/RWE in the US, particularly in relation to communications with payors about healthcare economic information (HCEI).  In January, the FDA released draft guidance for public comment to outline its thinking around communication to payors of HCEI, but there are still unanswered questions to be addressed in the final guidance.  Industry will need to quickly establish new policies and procedures to maintain compliance with the new regulations, especially in relation to OPDP submission requirements – a steep transition from a space that has largely been unregulated. 

1. ApotheCom Educational Series
What’s Next In US Payor Communications:
The Impact of FDA’s Proposed Guidance on
Communication of Healthcare Economic Information
March 23, 2017
New York | Philadelphia (Yardley) | San Diego | San Francisco | London | Dubai | Auckland | Shanghai | Singapore

2. For more than 15 years, Mr. White has been offering clients advice on global, US, and European market access and reimbursement
challenges. Nathan began his career at Express Scripts, working in leadership, field-based, and internal operational roles in the specialty
pharmacy and reimbursement support program divisions. He spent more than five years designing and implementing reimbursement
operational solutions at PAREXEL Consulting and inVentiv Health, before shifting into global market access consulting roles as Director of
Market Access at Nucleus Global and Managing Director and Head of Market Access at eMAX Health Systems. In 2016, he joined
ApotheCom to lead the Access Pathways and Outcomes practice. Nathan has a BS in Community Health from State University of New
York and is a Certified Professional Coder (CPC) in medical billing/coding.
Today’s
Presenter
● Environmental impact assessment
● Competitive analysis
● Internal value assessment workshops
About Us
ApotheCom, part of Huntsworth Health, is an integrated global medical affairs, RWE, and market access solutions firm, providing market
access and value research/analytics, medical education and marketing, and scientific publication services to the life sciences industries.
NATHAN WHITE, CPC
Executive Vice President and Global Practice Lead
Access Pathways and Outcomes
● Mixed method market research
● Advisory boards
● HTA/payor consultations
● HTA analysis
● Internal evidence assessment
● HTA/payor archetyping
● Burden of disease research
● Value message development
● Message resonance testing
● HTA submissions
● Value dossiers and payor comm. tools
● Outcomes-based contracting strategy
● RWE generation
● Health economic modeling
● Patient programs

3. Learning Objectives
Upon completion of this session, participants should be able to:
Understand history in communications of health economic information
in the US
Understand the proposed guidance by the FDA surrounding communications
with payors about healthcare economic information, related to both approved
and investigational drugs and medical devices
Relate the guidance to practical, operational, and organizational changes
that need to occur in medical affairs, market access, and HEOR departments
1
2
3
NOTE: Quotations throughout this training are derived from Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers. Guidance
for Industry and Review Staff. Published Jan 2017.

4. History of US HEOR Communications Policy
FDAMA first defined healthcare economic information (HCEI) in an amendment of the
FD&C Act (21 U.S.C. 352(s)) (section 502(a)).
For nearly 35 years, the health economics field continued to develop until it was formally
recognized in US health policy with the modernization of the FDA (FDAMA).
1930 2017
Food Drug
and Cosmetic
Act passed
FDA
Modernization
Act enacted
21st Century
Cures Act
enacted
Health
economics
field begins
1938 1963 1997 2016

5. CURES Provisions For Industry
CURES will change the review and approval process as provisions are implemented over the coming years.
Becoming law on December 13, 2016, CURES gives 7 key provisions to manufacturers,
viewed as mostly positive to industry interests.
Expedited review process for certain drugs
Facilitate recognition of drug outcome measures
Acknowledge RWE as a valuable tool for
regulatory approval
Priority Review Vouchers (PRV) for national
security threat countermeasures
Continuation of rare pediatric disease PRVs
Scope and appropriateness of HCEI
dissemination
Publication requirement of manufacturer
expanded access policies
• CURES requires FDA to develop and implement a framework for an RWE evaluation program
by end of 2018 (section 3022)
• Support approval of a new indication for an approved drug and support/satisfy post-approval study requirements

6. RWE Provisions in CURES
The design of the framework is left largely up to the HHS Secretary –
it may include public/private partnerships and 3rd party research organizations.
CURES requires the HHS Secretary to implement a framework for evaluation of RWE by
December 2018 and publish draft guidance on the program by December 2021.
1. Support approval for a
new indication for a
previously approved drug
2. Support or satisfy
requirements for
postapproval studies
PROGRAM GOALS
CONTENTS OF FRAMEWORK
• Sources of real world evidence, including ongoing safety surveillance,
observational studies, registries, claims, and patient-centered outcomes
research activities
• Gaps in data collection activities
• Standards and methodologies for collection and analysis of real world evidence
• Priority areas, remaining challenges, and potential pilot opportunities
Circumstances for use of RWE, standards, and methodologies
will be outlined in draft guidance from HHS.

7. Definition of HCEI
The guidance adds that HCEI can be presented in an evidence dossier, publication reprint,
budget impact model, or modelling software (not a comprehensive list).
“HCEI pertains to the economic consequences related to the clinical outcomes of treating a
disease (or specific aspect of a disease) or of preventing or diagnosing a disease.”
• Any analysis that identifies, measures, or describes the economic consequences
• Including the clinical data, inputs, clinical or other assumptions, methods,
results, and other components underlying or comprising the analysis
• May be based on the separate or aggregated clinical consequences of the
represented health outcomes, of the use of a drug
• Analysis may be comparative to:
• Use of another drug
• Another health care intervention
• No intervention

8. Introduction To Draft FDA Guidance
Guidance doesn’t establish legally enforceable responsibilities,
but describes FDA’s thinking and recommendations.
Guidance released in January 2017 aims to answer common questions surrounding communication of
HCEI to payors, formulary committees, and similar entities with expertise in healthcare economic analysis.
Communication of HCEI to payors regarding
approved drugs
Communications to payors about investigational
drugs and devices (investigational products)
1
2
Drug and Device Manufacturer
Communications With Payors,
Formulary Committees, and Similar
Entities –
Questions and Answers
Guidance for Industry and Review
Staff

9. Approved Drugs
Communication of HCEI by Firms to Payors
Regarding Approved Drugs

10. Potential Recipients of HCEI
“Other multidisciplinary entities” “review scientific and technology assessments to make drug selection, formulary
management, and/or coverage and reimbursement decisions on a population basis for health care organizations.”
In order to be considered an audience to receive HCEI, the audience should have significant
knowledge and expertise in healthcare economic analysis.
Payors Formulary
Committees
Technology
Assessment
Panels
Drug
Information
Centers
PBMsOther
Multidisciplinary
Entities
HCPs Consumers
NOT
COVERED

11. Evidentiary Support
CARSE standards apply to all components of HCEI, including clinical outcomes
(e.g. safety and efficacy).
Based on “competent and reliable scientific evidence”
Based on good research practices developed by “authoritative bodies”
(e.g. ISPOR, PCORI)
Must include study design, methodology, generalizability, limitations, sensitivity
analysis, and information to provide a “balanced and complete presentation”
HCEI considered NOT false or misleading
IF

12. What is CARSE and why is it important?
CARSE is important because it is the pre-established framework for determining is information is
false or misleading, and required by law in the context of communicating HCEI.
CARSE is “generally-accepted scientific standards, appropriate for the information being conveyed
that yield accurate and reliable results.”
SOURCES: https://www.ftc.gov/sites/default/files/attachments/training-materials/substantiation.pdf
COMPETENT
AND
RELIABLE
SCIENTIFIC
EVIDENCE
CARSE is:
• Tests, studies or other scientific research
• Based on expertise of professionals in field
• Objectively conducted by qualified people
• Using procedures accepted as accurate
CARSE is not:
• Anecdotal evidence from customers
• Newspapers or magazine articles
• Sales material
• Low return rate or money-back guarantee

13. HCEI Analyses Related To Approved Indication
FDA provides the above examples of HCEI analyses that could be considered
“related to an approved indication of a drug.”
HCEI analyses should relate to the disease/condition, manifestation of the disease/condition, or symptoms
associated with the disease/condition in the FDA-approved-label patient population.
Duration of treatment
Practice setting
Burden of illness
Dosing
Patient subgroups
Length of hospital stay
Validated surrogate endpoints
Clinical outcome assessments or other health
outcome measure
Persistence Comparisons

14. HCEI Analyses NOT Related To Approved Indication
The following HCEI analyses are not considered to relate to an approved indication.
An economic analysis of disease
course modification related to use of
a drug that is approved only to treat
the symptoms of the disease
HCEI analyses derived from
studies in patient populations that
are not within the indicated
patient population

15. What To Include
FDA provides guidance on the five key components to include as part of their communication
of HCEI in order to maintain compliance with the law.
Study design and
methodology
Generalizability
Limitations
Sensitivity analysis
Additional material for a balanced
and complete presentation

16. Study Design and Methodology
• Describe the study type (e.g., cost minimization analysis, cost-effective analysis,
cost-utility analysis, cost benefit analysis, cost-consequence analysis)
• Include the rationale for choice of the type of analysis
Type of analysis
• Describe modeling technique, choice, scope, key parameters/variables
• Rationale and consequences
Modeling
• Number of patients and relevant demographic information, such as age, gender,
ethnicity, clinical characteristics, and socio-economic statusPatient population
• Clearly stated so payors can understand the rationale of selection of inputs
• Guides audience to determine relevance to their healthcare organizations
Perspective/
viewpoint
1
2
3
4

17. • Other drugs, other medical care, no treatment
Treatment
comparator
• Relation to major clinical and economic outcomes (e.g. safety, efficacy, economic
consequences)Time horizon
• Describe clinical and non-clinical data sources
• Example measures: PROs, QALYs
Outcome measures
• Resource items for treatment pathway valuation, price/cost data sources
• Disclosure of manipulations and assumptions (e.g. currency conversions, inflation)
Cost estimates
• Information related to patient demographics or characteristics, natural disease
course, disease management/clinical practice, and cost of clinical eventsAssumptions
5
6
7
8
9
Study Design and Methodology

18. What does “balanced and complete presentation” mean?
In addition to information related to study design/methodology, limitations, generalizability, and sensitivity
analysis, FDA further details what should be included in order to be considered balanced and complete.
Conspicuous and
prominent
statement
describing
material
differences FDA-approved
indication/ FDA-
approved labeling
Disclosure of
omitted studies or
data sources
Risk
information
Financial/
affiliation
biases

19. COAs and Other Health Outcome Measures
Patient health status data capture methodology
and rationale for inclusion in analysis
Health outcomes valuation methodology and
appropriateness for patient population, disease,
and/or condition
1
2
These two aspects
should be considered
to “facilitate
interpretability and
comprehensibility of
the information:”

20. OPDP Requirements
“HCEI disseminated in accordance with section 502(a) is promotion, and, therefore, is subject to FDA’s
requirements for submission of promotional materials.”
“These include, but are not limited to, the
post-marketing requirement at 384 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 386
Advertisements and Promotional
Labeling for Drugs and Biologics for
Human 387 Use)”
“For HCEI about drugs submitted for
approval under the accelerated approval
pathway or about drugs approved based
on animal studies, the requirements
regarding pre-dissemination submission of
promotional materials”

21. Investigational Drugs and Devices
Communications by Firms to Payors Regarding
Investigational Drugs and Devices

22. Introduction
FDA provides much less guidance in communication with payors prior to FDA approval,
but does outline 7 key informational requirements.
“unbiased, factual, accurate, and non-misleading”
&
Product information
Information about the indication sought
Factual presentations of studies
Anticipated timeline for
approval/clearance
Product pricing information
Targeting/marketing strategies
Product-related programs/services

23. What additional information should be included?
FDA also suggest that manufacturers follow-up with payors as information becomes obsolete
due to new data and product information becoming available.
In addition to the 7 key informational requirements, FDA suggests that a investigational status
statement be accompanied by product development stage information.
“Clear statement that the
product is under investigation
and that the safety or
effectiveness of the product
has not been established”
“Information related to the stage
of product development”

24. Conclusion
Summary and Recommendations

25. Unanswered Questions
The public comment period ends on April 19, 2017; final guidance will be
published at a future unknown date.
ApotheCom will be working through questions and comments with key industry partners to identify
additional unanswered questions to submit to FDA during the public comment period.
Is FDA truly prepared for the additional workload for OPDP review of HCEI communications?
When and how frequently should a particular HCEI analysis be submitted to OPDP?
Do the required statements and supporting information need to be stated at every presentation of
each HCEI analysis, or just as the initial presentation? For example, does an abstract submission
containing HCEI need to include the supporting information if a poster will include the supporting
information? Will supporting information be required in an initial publication of a journal article?
Does clinical information from a pivotal trial become HCEI if it is used in the context of a model after
FDA approval?
Regarding communications with payors on investigational products, pricing and marketing strategies
may prove to be a challenge due to the highly sensitive nature of this information. How will industry
be assured confidentiality on these topics?

26. Key Learnings
The definitions of HCEI and payors are broad and therefore covers a wide range of study and analysis types, as well as
audience types.1
HCEI should not be false or misleading – in order to demonstrate that it is not, manufacturers should follow CARSE and good
practice guidance from authoritative bodies, as well as include detailed information on methodology, generalizability,
limitations, sensitivity analysis, and information to demonstrate a balanced and complete presentation.
2
HCEI should be related to an approved indication through one of a variety of analytical methods and study designs.3
HCEI communications with payors for approved products is considered promotional; thus, following regulatory guidance on
submission of promotional materials should be followed.4
Many unanswered questions remain related to practical implementation issues, particularly in relation to communication of
HCEI to payors on approved products.5

27. Nathan White, CPC
nathan.white@apothecom.com