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

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 UsApotheCom, 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, CPCExecutive 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

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.

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

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

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.

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

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

Approved Drugs

Communication of HCEI by Firms to Payors

Regarding Approved Drugs

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 ConsumersNOT

COVERED

Evidentiary SupportCARSE 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

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

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

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

What To IncludeFDA 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

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 consequencesModeling

• 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

• Other drugs, other medical care, no treatmentTreatment

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

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

differencesFDA-approved

indication/ FDA-

approved labeling

Disclosure of

omitted studies or

data sources

Risk

information

Financial/

affiliation

biases

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:”

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”

Investigational Drugs and Devices

Communications by Firms to Payors Regarding

Investigational Drugs and Devices

IntroductionFDA 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

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”

Conclusion

Summary and Recommendations

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?

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

Nathan White, CPC

nathan.white@apothecom.com