NPC Submits Comments to the FDA on Draft Guidance on Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities

April 19, 2017

Divisions of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane Rm 1061
Rockville Maryland 20852

RE: Draft Guidance on Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities. FDA-2016-D-1307


Dear Sir or Madam:

The National Pharmaceutical Council (NPC) shares the FDA’s interest in ensuring that information provided to payers is credible, reliable, truthful and non-misleading. Selection, coverage and reimbursement decisions by payers and other population health decision-makers impact many patients. These decisions often compare treatment options and affect more diverse patient populations, broader provider networks and different care settings than included in the typical FDA approval submission. High-quality decision-making requires access to truthful and non-misleading evidence. Sophisticated audiences such as payers and population health decision-makers need ready access to this evidence from all sources to make informed assessments and decisions as they budget, make coverage decisions and incentivize more efficient and high-quality care. For nearly a decade, NPC has worked to identify the constraints to disseminating evidence and to develop standards for credible, reliable, truthful and non-misleading information. We welcome the FDA’s comprehensive review of regulations and policies concerning the communication of evidence. 

NPC is a health policy research organization dedicated to the advancement of good evidence and science, and to fostering an environment in the United States that supports medical innovation. We are supported by the major U.S. research-based biopharmaceutical companies and focus on the critical issues of evidence, access, innovation and the value of medicines for patients. Our research helps inform critical health policy debates and supports the achievement of the best patient outcomes in the most efficient way possible.

We commend the FDA’s recognition that payers need additional and different information from the information traditionally included in FDA reviews. Our comments focus on the following six areas:

  1. Clarify the intended audience for health care economic information (HCEI) by including a broader range of organizations and individuals as examples of who can receive HCEI.
  2. Broaden the generally-accepted scientific practices recognized as competent and reliable scientific evidence (CARSE); confirm endpoints desired in a value-based payment environment are permissible to communicate.
  3. Permit pre-approval exchange of information for both investigational products and investigational indications for approved products.
  4. Ensure disclosures encourage transparent and timely communications without being overly prescriptive.
  5. Grant a promotional submission safe harbor to risk-sharing and value-based contracting HCEI discussions.
  6. Clarify differences in criteria and interpretation across multiple FDA guidance documents; and highlight the need for the FDA to lead coordination with the cross-agency interpretation of off-label and beyond-the-label communications.

We urge the FDA to carefully consider all comments received and to prioritize finalization of this guidance in an expeditious manner.

I. Clarify the Entities and Individuals Who Can Receive HCEI

  1. Entities Who Can Receive HCEI

NPC appreciates the additional clarification from FDA on the audience for HCEI under section 502(a) of the Federal Food, Drug, and Cosmetic Act. The audience for HCEI outlined in the draft guidance includes a broad array of entities. However, the organizations who are responsible for financing or reimbursement of treatments, the selection of drugs, and management of formularies are changing. Many stakeholders making population health recommendations, delivering care, and managing costs did not exist five years ago. For example, new care delivery models such as accountable care organizations — virtually unheard of 10 years ago — now provide care for nearly 28 million lives.[1] As clinical practice guideline groups and value assessment framework organizations evolve, they are expected to have a greater influence on providers, health plans and health systems.[2] Moreover, new delivery models and entities are likely as care is coordinated and the lines separating traditional health care organizations from payers are blurred.

Consider these examples:

  • An accountable care organization (ACO) needs to understand the overall health care cost and quality implications of including a drug on the formulary that reduces hip and vertebral fractures. Would the ACO be a “formulary committee or other similar entity” under the draft guidance? Would information exchange be permitted?[3]
  • An organization of providers is enrolled in the Center for Medicare and Medicaid Innovation Oncology Care Model. They are interested in the impact of different chemotherapy regimens on patient symptoms and quality measures. Would a provider organization developing care pathways be considered to select medications? Would risk-bearing providers responsible for meeting cost and quality of care benchmarks be eligible for information exchange?
  • A clinical practice guideline group aims to “include cost-effectiveness/value assessments and recommendations in practice guidelines and performance measures.”[4] Would clinical practice guideline organizations or value assessment bodies be considered “other multidisciplinary entities that review scientific and technology assessments?” Would information exchange be permitted?

The health care organizations and collaborations described above would meet the criteria outlined in the draft guidance. Each organization is 1) responsible for the recommendation, selection, and management of treatments on a population basis, 2) uses a deliberative process, and 3) has knowledge and expertise in the area of health care economic analysis.

NPC recommends that the FDA clarify the intended audience by including a broader range of organizations that meet the three proposed criteria as examples of appropriate audiences for receiving HCEI. This includes accountable care organizations, provider groups that share risk for patient costs and health, and technology assessment organizations such as clinical practice guideline groups and value assessment bodies.

  1. Include Individuals, Not Just Entities

The draft guidance defines the audience for HCEI to be entities or organizations, not health care providers making individual patient prescribing decisions. It is unclear if individuals who have multiple professional responsibilities, both caring for individual patients and advising population health decisions are included. Pharmacy and therapeutics (P&T) committees include both internal and external primary care and subspecialist providers.[5] Regulatory requirements for Medicare Part D and accreditation bodies such as URAC recommend P&T committees include practicing providers and pharmacists. At least one of the members must be “independent and free of conflict with respect to the Part D sponsor.”[6],[7] Some organizations even restrict voting membership to individuals who are not employees of their health plan or pharmacy benefits manager.[8]

Consider these examples:

  • If an individual advises a health plan P&T committee but is not a direct employee of the payor, are they eligible to receive truthful and non-misleading information?
  • Are individuals with multiple professional responsibilities eligible for information exchange when acting in their formulary or drug selection committee role?
  • Would individuals who are employees of a health plan and inform benefit design, but are not responsible for the selection of drugs, such as actuaries, be appropriate audiences for HCEI?

In each of the examples above, the individual serves as part of the “multidisciplinary entities that review scientific and technology assessments to make drug selection, formulary management, and/or coverage decisions on a population basis for health care organizations.”

NPC recommends that the FDA clarify that the intended audience for HCEI includes individuals who advise or inform the selection of drugs for population-based health decisions — not just organizational entities -- as long as the HCEI is not being communicated to these individuals in their capacities as health care providers making individual patient prescribing decisions.

II. Broaden the Generally-Accepted Scientific Practices Recognized as the Basis for CARSE; Confirm Endpoints Desired in a Value-based Payment Environment are Permissible

  1. Expand Standards Which Serve as the Basis for CARSE; Allow Flexibility for Future Methods Innovation

NPC welcomes the guidance on the evidentiary standards associated with competent and reliable scientific evidence (CARSE). Similar to the Federal Trade Commission definition, the draft allows a flexible standard for methods innovation based on the expertise of professionals in the relevant area.[9] Sources of evidence have evolved over time, and so too has the range of meaningful and scientifically valid evidence. As our evidence base continues to grow, we not only need to develop standards that work in 2017 — but standards sufficiently flexible for the data sources and analytic innovation in the future.

Over the past 5 to 10 years, there has been a proliferation of best practices and standards. A literature review published in 2016 found at least nine standards exist for conducting high-quality observational research studies. These standards and best practices were developed by a variety of disciplines (e.g., epidemiology, pharmacovigilance, and health economics) and organizations (e.g., professional societies, cross-stakeholder efforts, and governmental and non-governmental organizations).[10] While standards developed by the Patient-Centered Outcomes Research Institute (PCORI) and the International Society for Pharmacoeconomic and Outcomes Research (ISPOR) were identified in FDA's draft guidance, these are not the only recognized and generally-accepted good practices for observational research. For example, a multi-stakeholder group developed the Good ReseArch for Comparative Effectiveness (GRACE) Principles and GRACE checklist to help decision-makers assess the quality and usefulness of observational studies.[11],[12] The GRACE effort has been cited by a number of organizations including: the International Society of Pharmacoepidemiology, the Journal of Managed Care and Specialty Pharmacy, and United Kingdom National Institute for Health and Clinical Excellence. Similarly, NPC collaborated with the Academy of Managed Care Pharmacy (AMCP) and ISPOR, professional societies of experts in their respective areas, to create online tools and checklists to help population health decision-makers evaluate the relevance and credibility of new research methods. These checklists include techniques to assess if observational, modeling, and network meta-analysis studies are sufficiently credible based on good practices agreed upon by academic experts, industry researchers and payers.[13],[14],[15]

By limiting CARSE and the citations to authoritative bodies such as PCORI and ISPOR, these standards will de facto apply to all communications. However, these standards: 1) do not represent all accepted standards; 2) differ in their audience and purpose (e.g., researchers conducting studies vs. end-users evaluating the credibility and rigor of the study for decision-making); and 3) vary in the level of standards (e.g., best practice vs. minimum threshold). Singular citation of particular bodies can have unwanted risks: 1) research method innovations will stall and 2) studies conducted with up-to-date best practices may not be deemed to be “competent and reliable scientific evidence.”[10]

NPC recommends that the FDA reference additional generally-accepted scientific standards (e.g., GRACE Checklist and the ISPOR-AMCP-NPC Good Practice Task Force Reports among others). Standards should be flexible and iterative to facilitate research methods innovation.

  1. Payers and Risk-Bearing Providers Desire More Information Including Quality Measures

NPC commends the FDA on the recognition of the interdependence between the HCEI consequences associated with the use of the drug and the clinical information. Health care economic information is broader than the economic consequences alone. Most payers and risk-bearing providers are eager for more, and better, information. A survey of payers and risk-bearing providers found that between two-thirds and three-quarters of payers and providers feel at least somewhat limited by the amount, type, and the quality of information they receive.

Payers and providers utilize different outcomes and sources of information when making drug selection and coverage decisions. Between 60% and 90% of payers felt it was “extremely important” or “very important” to understand each of the following: the clinical benefits of treatments; how a treatment compares to alternatives based on information from either a clinical trial or high-quality, real-world study; whether patients reach quality outcome measures (e.g., asthma control or lipid goals); what side effects might occur; whether medication use is associated with changes in the utilization of other health care services; and the projected budget impact of treatment. However, when asked about the next three to five years, payers and risk-bearing providers felt the following measures would be of greater importance:[16]

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Besides the outcomes listed above, payers and risk-bearing providers recognize the increasing importance of information on treatment performance against quality measures. Quality measures help payers benchmark performance and are central to accountable care organizations and innovative payment programs such as bundled payments and risk-sharing agreements. Among payers, 53% agreed “completely” or “very much” that a product’s performance against quality measures would influence coverage decisions in the next three to five years. Only 12% did “not agree very much” or “not at all.” Among providers, 78% agreed “completely” or “very much” and 3% “did not agree very much” or “not at all.”[16]

NPC commends the FDA on the recognition that performance measures and clinical outcome assessment measures that are related to an approved indication are permissible forms of HCEI. In the shifting payment environment, explicit inclusion of quality measures, which are another form of performance outcome measures, as permissible types of HCEI would be a logical next step based on the agency's current position. Dissemination should be permissible even if the quality measure is not linked to an economic outcome.

III. Permit Pre-Approval Exchange of Information for Both Investigational Products and Investigational Uses of Approved Products

The draft guidance is an important first step for the exchange of pre-approval information. Payers need ready access to truthful and non-misleading evidence to aid them as they plan, budget, and forecast for new products and new indications. Payers routinely request information from manufacturers about investigational products and indications.[17] However, less than half of the payers receive this information. Even when information is provided, it is often too late to inform the review process.[18]

Timely information is needed well before product approval. For example, health plans are planning now for investigational products and supplemental indications with a potential 2018 FDA approval. Because insurance rates for the calendar year 2018 must be submitted 6-9 months in advance (e.g., spring 2017), lack of information or awareness may result in two unintended consequences. First, plans may underestimate the utilization and cost of new treatments resulting in premiums which do not cover costs. Second, plans may overestimate the utilization and costs of new treatments resulting in high premiums which discourage consumer decisions to purchase coverage.[19],[20]

The rationale for communications for investigational products applies equally to new indications for approved medications. It is not uncommon for products to be approved for one indication (e.g., advanced melanoma) and be under investigation for supplemental indications (e.g., non-small cell lung cancer, head and neck cancers, etc.). In 2014, the number of approvals for supplemental new indications was nearly equal to the number of new product approvals.[21] Most, if not all, of the information outlined in A.B.1 (starting at line 426 of the draft guidance) is specific to the indication rather than the product (e.g., indication sought, clinical data, and anticipated timeline for possible FDA-approval). If the new indication involves a different dose, frequency, or use (e.g., combination vs. mono-therapy), then product pricing information for the first indication will be inaccurate. Because product utilization and medication costs for supplemental indications may exceed those of the initial indication, plans need information at the indication- rather than the product-level.[22]

Strong incentives for continued evidence development and FDA approval exist. Payers use sophisticated approaches and make coverage policies based on the drug indication. A recent analysis of over 301 drug-indication coverage decisions by the 17 largest health plans found that 32% of all coverage decisions were more restrictive than the FDA-approved label (e.g., either do not cover, or policies are more restrictive than the FDA label). Coverage policies were consistent with the FDA-approved label for 58% of the decisions.[23] Incentives for evidence development will continue as reimbursement is often restricted for indications without sufficient evidence for payer decisions.

NPC agrees with the recommendations that emerged from the AMCP Partnership Forum on Enabling the Exchange of Clinical and Economic Data Pre-FDA Approval. The multi-stakeholder group noted that pre-approval information exchange was desired for both new medications and new indications of existing medications.[19]

NPC recommends that the FDA treat communication to payers regarding unapproved uses for approved products consistent with communications to payers regarding unapproved uses for investigational products.

IV. Ensure Disclosures Encourage Transparent and Timely Communication Without Being Overly Prescriptive

Contextual information about HCEI is important to allow readers a full understanding of the information relevance and credibility. However, disclosures need to be consistent with the format in which the HCEI is presented. In a recent survey, 65% of payers reported disclosure of study limitations to be “valuable” or “extremely valuable.” Just over half of the respondents found disclosures to be “valuable” or “extremely valuable” when the study or the information shared was not included in the FDA-label.[16] We agree that balanced and complete presentation of the material differences and the FDA-approved indication or labeling should be included.

However, the disclosures outlined in A.A.7 of the draft guidance may not apply to all HCEI communications and all study designs. For example, a study assessing patient persistence would not report the perspective of the analysis (e.g., health care system vs. society perspective). The credibility of a network meta-analysis is based on the search criteria to select studies for inclusion and the analytic methods to address potential differences in study design and populations — not the source of cost estimates.[13] Details can aid the understanding of a study population (e.g., “a clear description of …potential biases and/or confounders,” detailed clinical characteristics, and patient socioeconomic status, etc.). However, this level of detail far exceeds that contained in product labeling.

Disclosures meant to ensure that information is not false or misleading are overly prescriptive. We recommend that the elements for disclosures be based on the format of the communication and good practices agreed upon by payers, industry, and researchers.[13],[14],[15] The format for dissemination may vary. Appropriate disclosures should be accessible (e.g., as a cover page to the HCEI with a link to the study publication, analysis plan, or other relevant information), but not a part of the specific HCEI.

NPC recommends that disclosures should be based on the generally-accepted good practices for the study design and the format of HCEI dissemination. Study limitations and methods can be optimally provided through study documents (e.g., publication, analysis plan, etc.) rather than within the HCEI communication.

V. Grant a Safe Harbor to Risk-Sharing and Value-Based Contracting HCEI Discussions

NPC welcomes the agency’s recognition that HCEI may be shared in risk-sharing and value-based contracting discussions between firms and payers. Unclear regulation has slowed the negotiation and implementation of risk-sharing agreements.[24] However, the draft guidance is unclear if these conversations and exchanges would be deemed promotion and subject to FDA’s requirements for submission of promotional materials.

The foundation of risk-sharing agreements may be based on certain HCEI , such as the achievement of patient adherence to treatment, achievement of outcome targets (e.g., achievement of HbA1c Goal) or management of the total cost of care. However, regulating the communication of HCEI in the context of negotiating risk-sharing and other value-based contracts does not make sense from either a logistical or policy perspective. Submission of such endpoints, models, and analyses to FDA using Form FDA 2253 could disclose confidential contractual terms and negotiations. Moreover, the communication of HCEI in this context--in order to arrive at precise terms in a transaction--is distinguishable from the broader promotional context in which this information is typically shared with payers and that is addressed by the draft guidance. As others have highlighted, these contracts should be granted certain legal and regulatory safe harbors.[25] Submission of risk-sharing and value-based contract discussion materials to FDA are one such safe harbor that should be enacted.

NPC recommends that risk-sharing and other value-based agreements should be granted safe harbor from promotional submission requirements to avoid improper disclosure of confidential contract terms between firms and payers.

VI. Clarify Differences in Criteria Across Multiple FDA Guidance Documents

  1. Delineate Difference in Criteria Across Multiple FDA Guidance Documents

The relationship of HCEI to the approved indication has long been a source of ambiguity.[3],[26],[27] The revised language in Section 3037 of the 21st Century Cures Act and illustrative examples outlined in A.A.4 in the draft guidance provide greater clarity. However, there is a lack of clarity across recent FDA draft guidance documents. For example, the Draft Guidance on Medical Product Communications That Are Consistent With the FDA-Required Labeling outlines three factors for communications to be “consistent with the product’s FDA-required labeling.” The relationship between “consistent with labeling” and “relates to an [approved] indication" are unclear. Are there examples where information would meet criteria in one guidance but not the other?

NPC recommends that the agency provide guidance on the relationship between “relates to” and “consistent with” the approved indication to reduce the ambiguities associated with multiple regulatory documents.

  1. Cross-Organizational Acknowledgement of FDA-Leadership

Multiple government agencies  including the Federal Trade Commission, the Department of Health and Human Services Office of the Inspector General, the Department of Justice, and state attorneys general have enforcement authority regarding off-label or beyond-the-label communication.[28],[29] HCEI communications permissible under FDA guidance may have different interpretation by other agencies.[30],[31] While some experts note that communications permitted under a regulation or guidance document cannot be the basis for a False Claims Act, the potential time, staff and legal fees associated with even the threat of action may chill the intended effects of FDA draft guidance.[31] Without cross-organization acknowledgement, provisions designed to enable communication between firms and payers may be dampened.

NPC recommends that the FDA seek to lead coordination across other government agencies with the goal of having other agencies acknowledge the FDA’s leadership over the issues contained within this guidance.


We appreciate this opportunity to provide input on the Draft Guidance on Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities. The communication of health care information is now more important than ever. The products available to treat conditions, the ways health care is organized, delivered and reimbursed, and the information sources and analytic processes available have become more sophisticated. Now is the time for regulations and guidance for communication to evolve in parallel. NPC looks forward to participating in the dialogue to advance the development and communication of good evidence and science. We stand ready to address any future comments as the draft guidance is finalized. Thank you for the opportunity to provide these comments.

Respectfully submitted,


Jennifer S. Graff, PharmD
Vice President, Comparative Effectiveness Research
National Pharmaceutical Council


Robert W. Dubois, MD, PhD
Chief Science Officer
National Pharmaceutical Council

[1] Muhlestein D, McClellan M. Accountable Care Organizations in 2016: Private and Public-Sector Growth and Dispersion. Health Affairs Blog. April 21, 2016. Available at: Accessed: March 21, 2017.

[2] Westrich K. Current Landscape Value Assessment Frameworks. June 2016. Available at: Accessed March 25, 2017.

[3] Neumann PJ, Saret CJ. When Does FDAMA Section 114 Apply? Ten Case Studies. Value in Health. 2015; 18:682-9.

[4] Anderson JL, Heidenreich PA, et al. ACC/AHA Statement on Cost/Value Methodology in Clinical Practice Guidelines and Performance Measures. JACC. 2014; 63(21)2304-22.

[5] Leung MY, Halpern M, West ND. Pharmaceutical Technology Assessment: Perspectives from Payers. J Manag Care Pharm. 2012; 18(3):256-64.

[6] URAC Pharmacy Benefit Management Standards Version 2.0. Pharmacy & Therapeutics/Formulary Development Standards 4 P&T Committee Membership. Available at Accessed March 25, 2017.

[7] Medicare Prescription Drug Benefit Manual. Section 30.1.1. Membership. Chapter 6–Part D Drugs and Formulary Requirements. Available at Accessed March 23, 2017.

[8] CVS Caremark Formulary Development and Management at CVS Caremark. Available at: Accessed March 23, 2017.

[9] Garrison LP, Neumann PJ, Radensky P, Walcoff SD. A Flexible Approach to Evidentiary Standards for Comparative Effectiveness Research. Health Affairs. 2010; 29(10):1812-1817.

[10] Dreyer NA, Schneeweiss S, McNeil BJ et al. GRACE Principles: Recognizing High-Quality Observational Studies of Comparative Effectiveness. Am J Manag Care. 2010; 16(6):467-71.

[11] Dreyer NA, Velentgas P, Westrich K, Dubois R. The GRACE Checklist for Rating the Quality of Observational Studies of Comparative Effectiveness: A Tale of Hope and Caution. J Manag Care Phar. 2014; 20(3):301-8.

[12] Jansen JP, Trikalinos T, Cappelleri JC, et al. Indirect Treatment Comparison/Network Meta-Analysis Study Questionnaire to Assess Relevance and Credibility to Inform Health Care Decision Making: An ISPOR-AMCP-NPC Good Practice Task Force Report. Value in Health. 2014; 17(2):157-73.

[13] 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 in Health 17(2):143-56.

[14] Caro JJ, Eddy DM, Kan H et al. Questionnaire to Assess Relevance and Credibility of Modeling Studies for Informing Health Care Decision making: An ISPOR-AMCP-NPC Good Practice Task Force Report. Value in Health. 2014; 17(2):174-82.

[15] Morton SC, Costlow MR, Graff JS, Dubois RW. Standards and Guidelines for Observational Studies: Quality is in the Eye of the Beholder. J Clin Epidemiol. 2016; 71:3-10.

[16] National Pharmaceutical and Xcenda Survey. Pharmaceutical Information Exchange Survey. n=51 payers; n=31 providers in an accountable care organization or under a shared risk agreement.  April 2017.

[17] Dymaxium Decision Maker/Manufacturer Exchange of Informatio