NPC Testimony on Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products

National Pharmaceutical Council Testimony As Prepared for Delivery by Jennifer Graff, PharmD

FDA-2016-N-1149 Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products; Public Hearing; Request for Comments

Thank you for the opportunity to provide input on issues related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.[1] At the National Pharmaceutical Council (NPC), we believe it is important for all stakeholders to work together to understand how treatments work in the real world. This evidence is central to guiding population health decision-makers as they budget, make coverage decisions, and incentivize more efficient and high-quality care. Understanding the constraints on sharing evidence and identifying standards for credible, reliable, truthful, and non-misleading evidence has been at the forefront of our work for the past several years. Therefore, 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.

Today, I would like to comment on two issues.

  1. Public Health Goals and Health Care Reform Initiatives Require Broader Communication

To achieve our shared goal of a high-performing, value-based health care system, informed and evidence-based decisions are needed. Greater efficiency and better care requires more information exchange—not less—about which treatments work best for whom and under which care settings.

However, the laws and regulations regarding what information exchange is permitted are numerous and ambiguous. Provisions such as Section 114 of the Food and Drug Administration Modernization Act of 1997 (FDAMA Section 114) intended to facilitate this exchange have instead resulted in uncertainty.  

Consider the following examples:

  • An accountable care organization (ACO) needs to understand the overall health care cost and quality implications of including a drug on a formulary list that reduces hip and vertebral fractures. Would information exchange be permitted, and would the ACO be considered a “formulary committee or other similar entity” under FDAMA Section 114?[2]
  • A health plan is interested in developing a value-based contract based upon hospital readmission rates for lung disease. Can information on outcomes that are relevant to a health plan, but not included in the FDA label, be shared?
  • Can payers and other groups who are financially rewarded for meeting quality goals receive information about a product’s ability to help achieve a quality outcome measure, such as the percentage of patients reaching asthma control, if the results are from a credible and reproducible study among patients in the real world?
  • If a biopharmaceutical company compares the effectiveness of two migraine treatments on outcomes that matter to employers and patients, will the biopharmaceutical company be able to communicate the results in the same manner as the public not-for-profit Patient-Centered Outcomes Research Institute?[3],[4]

These scenarios provide an impetus for manufacturers to develop high-quality data to inform population health decisions. Although randomized controlled trials may be able to answer some questions, other study designs, such as real-world studies, may be a better fit to address real-world effectiveness.

  1. Standards and Best Practices Exist and can be Relied on to Ensure Scientific Integrity

There has been a proliferation of best practices and standards for conducting observational or real-world studies over the last 5 to 10 years. These include initiatives in which NPC has had an opportunity to be involved, such as the Good ReseArch for Comparative Effectiveness (GRACE) Principles[5] and GRACE checklist[6] that identify features associated with high-quality observational studies. NPC also collaborated with the Academy of Managed Care Pharmacy and the International Society for Pharmacoeconomics and Outcomes Research, 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 studies using different research designs. These tools include techniques for assessing observational, modeling, and network meta-analytic studies that would not typically meet the substantial evidence threshold.

To date, these tools have more than 3,000 users among pharmacy, biopharmaceutical, and managed care professionals. In addition, a 19 credit hour training program has been developed to ensure sophisticated professionals have the confidence and ability to critically evaluate the credibility of these new types of studies for coverage, reimbursement, and care pathway decisions.[7]

We are not the only group engaged in these efforts. In partnership with the University of Pittsburgh Medical Center, we compared nine different guidelines and standards for conducting observational or real-world studies developed by public, private, and professional organizations in the U.S. and Europe.[8] This work provides insight on the level of scientific integrity required for credible, reliable, truthful, and non-misleading evidence.

In closing, NPC shares the goal of the FDA: to ensure that communication is done in a way that promotes public health and supports ongoing developments in science and technology, medicine, and health care delivery. Meeting these goals requires transparent, reproducible, and ongoing evidence generation and communication. Improved communication includes sharing what is known about the benefits and risks of a treatment, along with the limitations of that evidence. [4],[9]

In a world in which less than 4 percent of patients enroll in clinical trials, permitting communication of truthful and non-misleading evidence—rather than restricting communications—can encourage our transition to a learning health care system that rewards value. The National Pharmaceutical Council looks forward to submitting our full written comments, and we stand ready to provide additional information.


[1] 81 FR 60229. Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products; Public Hearing; Requests for Comments. Proposed Rule by the Food and Drug Administration. September 1, 2016.

[2] Neumann PJ, Saret CJ. When Does FDAMA Section 114 Apply? Ten Case Studies. Value in Health. 2015;18:682-689.

[3] Dentzer S. Communicating about comparative effectiveness research: a Health Affairs symposium on the issues. Health Aff (Millwood). 2012;31(10):2183-87.

[4] Perfetto EM, Bailey JE, Gans-Brans KR et al. Communication About Results of Comparative Effectiveness Studies : A Pharmaceutical Industry View. Health Aff (Millwood). 2012;31(10):2213-2219.

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

[6] 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.

[7] Perfetto EM, Anyanwu C, Pickering MK, Zaghab RW, Graff JS, Eichelberger B. Got CER? Educating Pharmacists for Practice in the Future: New Tools for New Challenges. J Manag Care Spec Pharm. 2016;22(6):609-16.

[8] Morton SC, Costlow MR, Graff JS, Dubois RW. Standard and guidelines for observational studies: quality is in the eye of the beholder. Journal of Clinical Epidemiology. 2016;71:3-10.

[9] AMCP Partnership Forum: FDAMA Section 114-Improving the Exchange of Health Care Economic Data. J Manage Care Spec Pharm. 2016;22(7):826-31.