June 17, 2019
Re: AMCP Format for Formulary Submission Version 4.1: Call for Comments
The National Pharmaceutical Council (NPC) commends the Academy of Managed Care Pharmacy (AMCP) and the Format Executive Committee on the revised AMCP Format for Formulary Submissions Version 4.1. As a health policy research organization dedicated to the advancement of good evidence and science, we are pleased to see the Format’s revision and alignment with the 2018 Food and Drug Administration (FDA) Guidance Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities. While the 2018 FDA final guidance provides an important step forward to modernize health care communications, parallel efforts to operationalize the pathways to exchange of high-quality and robust information between biopharmaceutical manufacturers and health care decisionmakers determining coverage are needed. The Format advances this shared vision.
Our comments address the questions outlined by AMCP and emphasize three issues:
- Underscore the importance of bi-directional rather than unidirectional feedback,
- Highlight the need to include caveats regarding the availability of evidence at various points in a product’s lifecycle, and
- Ensure consistency with the FDA Final Guidance.
Question 1: Please provide feedback on whether the role of the Format is accurately conveyed based on current Food and Drug Administration guidance and the current state of communications between manufacturers and payers.
NPC applauds the Format’s recognition of the need for bi-directional exchange of timely, quality, and relevant clinical and economic information between biopharmaceutical manufacturers and health care decision-makers. New and innovative medicines bring value to patients and our health system. We recommend additional work to ensure the process facilitates clear, transparent, bi-directional communication rather than a uni-directional submission of information. Developing efficient and high-quality evidence to meet the varying needs of diverse stakeholders, including health care decision-makers is a time and resource-intense activity. Clarity in the information ultimately considered (or disregarded) in the budgeting, forecasting, and coverage determinations can improve the evidence developed and communicated.
Question 2: General Definitions and Considerations: AMCP has updated definitions upon new FDA guidance. This section also outlines the communication process between manufacturers and HCDMS. Do these definitions properly convey the current state of communications based upon the FDA guidance? In particular, please provide feedback on whether Table 1 is helpful in conveying requirements in a concise manner. In addition, are the terms pre-approval information dossier, post-approval dossier, and new indication dossier helpful in being able to convey this information?
NPC appreciates the comparisons outlined in Table 1 describing pre-approval information dossiers, post-approval dossiers, and new indication dossiers. Clarity in the descriptions will help to inform users and reviewers reviewing at-a-glance descriptions. To aid this, we suggest these modifications or clarifications:
- We recommend replacing the terms proactive and reactive communication with solicited and unsolicited requests to ensure consistency with the FDA guidance. Proactive and reactive communications are not defined elsewhere in AMCP Format nor the FDA final guidance. Further, as noted in footnote 57, the final FDA guidance does not to supersede the draft guidance for Responding to Unsolicited Requests for Off-Label Information About Prescription Drugs and Medical Devices when payors make unsolicited requests to firms. We recommend the Format use consistent terminology with the FDA guidance documents.
- We recommend adding a row that includes describes the dossier ability to communicate the value of a product. Traditional AMCP post-approval dossiers allow the manufacturer to communicate the value of a product based on evidence-based medicine principles. Pre-approval or unapproved indication dossiers do not make characterizations or conclusions.
- We recommend the Format remain silent on who from the manufacturer should communicate or provide a dossier. Appropriate training and expertise are critical to optimizing the exchange of relevant and credible information. However, who provides this information should be at the manufacturer’s discretion for two reasons. First, there is not a parallel requirement that health care decisionmakers, payers, or entities that make or influence formulary, coverage, policy, or reimbursement decisions have appropriate medical credentials or expertise to receive this information. Second, and most critical, the FDA has remained silent on who should communicate or provide a dossier. Differences in recommendations between the FDA guidance and that included in the Format may lead to confusion between both. This table should be amended to align with the FDA guidance. If discrepancies remain, documentation and footnotes outlining where the Format goes beyond the FDA guidance are needed.
- We recommend clarifying that anticipated product price is reflected as a price corridor as outlined in Section 1.1 Table of Highlights for Unapproved Product. Final product pricing considers registrational trial results and the final FDA-approved labeled population and indication. Requiring specific pricing information rather than price corridors early in the clinical trial development process (e.g., 24 months prior to product approval) is likely to impede rather than aid forecasting and budget calculations.
- We recommend similar clarifications regarding price corridors for unapproved indication dossiers consistent with the information outlined in Section 1.2 Table Highlights for Unapproved Use of an Approved Product. For some products, the anticipated annual cost per patient may vary based on the FDA-approved dosages for each indication. For other products, novel payment schemes such as indication-based pricing may alter the anticipated annual cost per patient. Finally, footnotes specifying that pricing information is provided based on manufacturer discretion are warranted. These notations and clarifications can help align expectations between both manufacturers and health care decisionmakers.
Question 3: Updating Dossiers: Does this section properly convey information for updating dossiers?
NPC appreciates the additional guidance on when a product dossier should be updated. We propose two clarifications:
- We agree dossiers should be reviewed and updated when there are significant changes to the prescribing information, line extensions, new safety information or any information that materially affects the overall evidence. However, a complete revision should not be required for all significant changes. For example, a product label expanding use among females with breast cancer to include use among males with breast cancer is a significant change to the prescribing information. However, much of the baseline product description, disease description, unmet need and approaches to treatment will be similar and not require a “complete” revision.
- NPC recommends developing a mechanism to ensure health care decisionmakers review the most up-to-date information (e.g., in Appendix A). As outlined in the Format Version 4.1, evidence evolves as products move from pre-approval to post-approval. Updating the corollary information is labor and time intensive, requiring special care to ensure up-to-date information is available for decisionmakers. Thus, it is critical that health care decisionmakers use the same up-to-date information not only to justify these resource investments but also to ensure the decisions ultimately affecting patients are based on current information.
Question 4: Are there any other general comments you would like to add?
We offer three comments:
- We appreciate the additional guidance and limited provisions provided to streamline public comment. However, in the select provisions, it is unclear whether the elements outlined on pages 16-21 reflect the “Evidence Requirements for Pre-Approval Information Dossier and Unapproved Indication Dossiers,” or the evidence requirements for all dossiers. If intended for all dossiers, such provisions may be appropriate. If intended for pre-approval or unapproved indication dossiers, several items outlined may not be relevant until closer to the product or indication approval. These include:
- Section 2.1:
- Item 10. All dosage forms, including strengths and package sizes;
- Item 13. FDA-approved contraindications/warnings/precautions/adverse events;
- Item 14. Special populations (e.g., pregnancy, pediatric use, renal impairment);
- Item 15. Interactions with suggestions on how to avoid them;
- Item 17. Prescribing restrictions;
- Item 20. Product-related programs or services, e.g., patient support programs;
- Item 22. Product pricing information.
- Section 2.1.1
- Product comparisons demonstrating biosimilarity or interchangeability should be limited to factual comparisons.
- Section 2.5.8
- “anticipated outcomes of therapy (e.g., a cure, palliation, relief of symptoms, quality of life, patient-reported outcomes, productivity, etc.” As outlined in A.C.1 in the FDA guidance, characterizations beyond the study results would not be appropriate.
- Section 2.1:
- We recommend Section 4.0 Economic Value and Modeling Report adopt the recommendations from the Second Panel on Cost-Effectiveness in Health and Medicine. These recommendations reflect the current state of cost-effectiveness analyses and were developed through active participation of health economists, extensive external review and public comment periods. We recommend key changes from the Second Panel (e.g., the need to utilize a reference case to encourage comparability and quality of cost-effectiveness analyses, inclusion of a societal perspective as a co-base case, assessment of the impact inventory of the societal impact, and improvements to the transparency and sensitivity analyses of cost effectiveness) are recognized in the Format Version 4.1. Final recommendations from the October 2016 Second Panel were not yet publicly available at the release of the prior Format Version 4.0.
- We recommend AMCP engage with the FDA to ensure the Format Version 4.1 aligns with the FDA’s current thinking and guidance on communications between manufacturers and payers and the unsolicited request process. Without reassurance from the FDA — even informally — provisions meant to modernize and encourage clear, transparent and bi-directional communications are likely to be dampened due to concerns regarding regulatory compliance and regulations.
At a time when new and novel treatments are curing diseases and reimbursement is based on quality and value rather than volume, clear communication channels between innovators and decisionmakers are needed. NPC applauds the leadership of AMCP to modernize the bi-directional communications of credible information between biopharmaceutical companies and health care decisionmakers. NPC looks forward to answering questions and working as a partner to advance the development of good evidence and science for coverage determinations for innovative treatments.
Jennifer Graff, PharmD
Vice-President, Comparative Effectiveness Research
 Sanders GD, Neumann PJ, Basu A, et al. Recommendations for Conduct, Methodological Practices and Reporting of Cost-effectiveness Analyses Second Panel on Cost-Effectiveness in Health and Medicine. JAMA. 2016. 316(10):1093-1103.