The past decade has seen a surge in medical advancement resulting in innovative therapies addressing unmet needs in rare and orphan diseases or demonstrating superior efficacy over existing therapies. The Food and Drug Administration (FDA) has responded by supporting access to these therapies with fast-track, collaborative new drug and biologic application review processes.

Health care payers have the challenge of determining coverage policies for the high number of innovative therapies that come to market. They rely on available clinical and economic evidence, when available, to plan and budget for future coverage and/or reimbursement for unapproved products and new uses of approved products. Payers increasingly need this information sooner to inform these challenging population-level coverage and access decisions.

What is Pre-approval Information Exchange?

Pre-approval Information Exchange (PIE) is the exchange of information between pharmaceutical manufacturers and payers about an unapproved drug, or an unapproved use of an approved drug. The FDA has provided guidance on communicating pre-approval information, most notably in its guidance on payor communications published in 2018.1 Moreover, the PIE Act of 2022 was signed into law on December 29, 2022 as part of the Consolidated Appropriations Act, 2023 (H.R. 2617), which codifies key elements of appropriate pre-approval information exchange.2

Below is our guide to some of the key considerations when providing pre-approval information related to the guidance.

Key considerations when communicating PIE

Key questionsUnapproved product/Unapproved use (PIE)
When can information be delivered?Anytime before indication approval
What information can be communicated?The guidance and law provides specific guidance as to what can be communicated, including disease information, clinical evidence, stage of development, and limited pricing and anticipated utilization data.
Who can deliver pre-approval information?The guidance does not specify who can (or cannot) deliver pre-approval information to payer audiences.
Who can receive pre-approval information?Payers, formulary committees, or other similar entities with knowledge and expertise in health care economic analysis, carrying out its responsibilities for the selection of drugs for coverage or reimbursement.
The guidance does not apply to dissemination of health care economic information to other audiences, such as healthcare providers making individual patient prescribing decisions.

What type of pre-approval information can manufacturers communicate?

Manufacturers should communicate pre-approval information that is unbiased, factual, and accurate. The information must not be misleading.

Disease: A description of the disease should include relevant epidemiology, risk factors, pathology, clinical presentation, burden of disease (e.g. societal, humanistic, health care resource utilization, economics) and how the disease is diagnosed.

Clinical: Factual presentations of study results should be communicated in an unbiased way with no conclusions regarding the safety or effectiveness of the unapproved product. Payers need to understand the study design as well as any limitations related to the study design, methodology and results. The study endpoints and rationale, patient inclusion and exclusion criteria, subpopulation analysis of safety and efficacy (if available), reasons for patients discontinuing the study, and the indication being sought.

Stage of product development: Include details about the status of any study/studies in which a product/new use is being investigated and how it relates to the overall product development plan. Detail whether a marketing application for the product or new use has been submitted to the FDA or when such a submission is planned.

Economic information: Under FDA guidance, manufacturers may provide product pricing information. As advised by the Academy of Managed Care Pharmacy (AMCP) Format 4.1, the manufacturer has discretion on whether and how to provide economic information.3

Product information: Include drug class, administration and whether the drug must be administered by a healthcare professional, whether the drug is likely to be dispensed through a specialty pharmacy and whether distribution will be limited. Include information about whether there will be a risk evaluation and mitigation strategies (REMS) program, a description of patient assistance programs, and to whom the drug will be marketed – only to specialists or also to primary physicians.

Notably, PIE communications regarding unapproved drugs must include a clear statement that the product or use is not approved/cleared/licensed, and that the safety or effectiveness of the product or use has not been established.

For unapproved uses of an approved drug, PIE communications must include a prominent statement disclosing the indication(s) for which the FDA has approved, cleared, or licensed the product and a copy of the most current FDA-required labeling.

What not to include: Manufacturers must not represent that an unapproved drug or the unapproved use of an approved drug is safe or effective for the use for which it is being studied.

How to communicate PIE

A well-developed internal process should be developed to ensure appropriate roles and responsibilities in delivering PIE compliantly. Regardless of who is delivering PIE, it should be noted on the document being shared that it is for the communication of PIE to an appropriate payer audience.

Pre-approval information can be communicated in person or virtually using a variety of tools, examples include payer presentations and AMCP pre-approval dossiers.

When to communicate PIE

The timing of when payers receive pre-approval information can influence access to a product. Many payers actively review the clinical pipeline to prepare for new drug releases and new indications. They are often evaluating new drugs close to FDA approval. Manufacturers that do not engage in PIE lose the opportunity to gain early payer feedback and insights on their products.

Manufacturers should consider the communication of pre-approval information at least 6 months before the expected FDA approval. If the disease state or therapy is particularly complicated, initial conversations should start as early as 12–18 months before the approval date. Earlier engagement between manufacturers and payers provide the most favorable circumstances for earlier patient access.

Why is having a PIE strategy important?

Early internal alignment on a process for PIE communications may ensure the tools used to facilitate information exchange, i.e., a PIE payer presentation slide deck and/or AMCP pre-approval dossier, can be developed in a compliant and timely manner. The process should include multiple internal departments such as Market Access, Medical Affairs, Legal and Regulatory.

Different payers may be best served by using different tools. A PIE payer presentation slide deck is useful for in person or virtual meetings between manufacturers and payers. An AMCP unapproved product/unapproved use dossier provides all the information in one place and may be best for payers for whom an in person/virtual meeting with the manufacturer is not feasible or as a follow-up reference to support ongoing discussions. It is critically important that manufacturers plan early for developing and communicating these payer evidence tools.

PIE provides the opportunity for pharmaceutical manufacturers to proactively communicate with payers and to elicit payer feedback about their products. Having an internal process to generate timely data, create tools, and engage payers in PIE is a key component for a successful product launch. Early dialogue between payers and manufacturers is critical for the success of both entities.

More on this topic

This article is part 2 of a series on ‘Opportunities for Enhanced Communication between Manufacturers and US Payers’. You can access part 1 of the series here.

References

  1. Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities; Questions and Answers; Guidance for Industry and Review Staff. Available at: Guidance for Industry (fda.gov). Last Accessed December 9, 2022.
  2. Pre-approval Information Exchange Act of 2022. Available at: Text – H.R.7008 – 117th Congress (2021-2022): Pre-approval Information Exchange Act of 2022 | Congress.gov | Library of Congress, on 10/10/2022. Last Accessed December 9, 2022.
  3. AMCP. AMCP Format for Formulary Submissions – Guidance on Submission of Pre-approval and Post-approval Clinical and Economic Information and Evidence, Version 4.1. April 20, 2020. Available at: AMCP Format for Formulary Submissions — Guidance on Submission of Pre-Approval and Post-Approval Clinical and Economic Information and Evidence, Version 4.1 | AMCP.org. Accessed on January 18, 2023.

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