White Paper | Pre-Approval Information Exchange (PIE)

SPRING 2021, THE EVIDENCE FORUM, WHITE PAPER

Donald Smith, PhD
Senior Scientific Director
Evidence Synthesis, Modeling & Communication
Evidera, a PPD business

The use of pre-approval information exchange (PIE) has been on the rise the past couple of years. While the final version of the US Food and Drug Administration’s (FDA) Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers Guidance for Industry and Review Staff released back in June 2018 really set things into motion, the release of Version 4.1 of the Academy of Managed Care Pharmacy (AMCP) Format for Formulary Submissions in December 2019 has led to an expanded use of PIE and an increased demand for pre-approval AMCP dossiers (i.e., Unapproved Product Dossiers and Unapproved Use Dossiers), PIE slide decks, and other PIE materials.^1,2

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What is PIE?

PIE is information that can be shared with healthcare decision makers (HCDMs), such as payers, prior to the FDA approval of a new product (i.e., an unapproved product) or a new indication for a currently approved product (i.e., an unapproved use).² It does not require an unsolicited request from an HCDM and is typically shared in a proactive manner.^1,3

Why Do HCDMs Want PIE?

HCDMs want to receive information about new products and new indications prior to FDA approval.^1,2 Such information helps HCDMs to more accurately plan for future drug approvals and reimbursement decisions, and forecast their future budgets.¹

Information Related to Product Pricing

While HCDMs would like information on the price of a product, it is seldom provided by manufacturers prior to FDA approval. That being said, if a manufacturer is seeking a new indication for a currently approved product, the known price of the approved product should be included in PIE materials.¹ If the price of a new indication of an approved product is expected to be different than the price of a currently indicated use, this should be mentioned.¹

If a specific price is not available, or if the manufacturer chooses not to share it, there are other pieces of economic information such as price ranges, economic models, and target patient population sizes that HCDMs consider useful for forecasting their budgets.^1,2 While a price range may be provided by manufacturers, and Version 4.1 of the AMCP Format provides example price ranges that can act as a guide, this approach is uncommon.¹ Similarly, most manufacturers do not share economic models as part of PIE materials, potentially because they may include outcomes or assumptions related to the effectiveness and/or safety of the unapproved product or indication.¹ In contrast, providing an accurate estimation of the size of the target patient population is a common approach. Sharing this information can give HCDMs an idea of how many people will realistically make use of a new product or indication.

Other Types of Information

In addition to information related to product pricing, HCDMs are also interested in receiving other types of information: general information about the product, information about the clinical studies supporting the product, and the timelines for product approval.^1,2 Knowledge about the product and its key clinical studies makes HCDMs aware of which products are seeking FDA approval, and the timelines for FDA approval let HCDMs know when a new product or new indication will start to directly affect their budgets.

Why Should Manufacturers Share PIE?

Even though manufacturers are not required to develop and share PIE materials,^1,2 doing so can provide many benefits. Providing PIE materials allows the manufacturer to raise awareness and share information about new products and new indications prior to FDA approval. It is also possible that providing PIE may help manufacturers gain access, achieve earlier access post-approval, and prevent unwanted restrictions.³

If manufacturers choose to provide PIE to HCDMs, HCDMs will not only have knowledge about new products and new indications, but also be able to compare them. Using PIE, HCDMs can compare new products with products that are already approved. In addition, PIE also allows HCDMs to compare two unapproved products with different timelines for FDA approval.³ If one manufacturer is expecting product approval in six months and another is expecting approval in two months, providing PIE will allow HCDMs to review both products simultaneously, despite the difference in FDA approval timelines.³ In fact, it is possible that HCDMs may ultimately choose to pay for the product with the longer approval timeline instead of the product with a shorter approval timeline if they feel that it provides more benefits to patients.³

What Information May Be Shared in PIE Communications?

Information that can be shared during PIE discussions has been outlined by the FDA and includes:²

Product information (e.g., mechanism of action)
Information about the indication(s) being sought
Information about the patient population being examined
The anticipated timeline for FDA approval of the new product or indication
Information on product pricing
Patient utilization projections and/or prevalence data
Product-related programs or services and patient support programs
Factual presentations of the design and results of clinical studies

While the focus of PIE communications is generally on the manufacturer’s product, information on the current state of the field in general (e.g., disease burden, unmet need, current treatments, treatment guidelines) can be included in PIE communications. While sharing information on treatment guidelines is not specifically mentioned in the FDA guidance or Version 4.1 of the AMCP Format,^1,2 most manufacturers choose to share this information so that HCDMs can start to think about how a new product or new indication will fit into the current treatment paradigm. For example, if the product will be used after another therapy or in place of another therapy.

Thus far, most of the information that has been included in PIE communications has been publicly available. While data on file can be shared at the discretion of the manufacturer,¹ most manufacturers have chosen not to share data on file in PIE communications. This is partially due to concerns about confidentiality.³ However, developing PIE materials has provided a reminder that there are many publicly available sources of information that can be shared as part of PIE communications. Press releases, published manuscripts, information from ClinicalTrials.gov, published study protocols, response letters from manufacturers’ medical information departments, and conference abstracts, posters, and oral presentations have all found their way into various PIE materials.

While a value proposition may be used to guide the type of information that will be used to develop PIE, it cannot be directly incorporated into PIE materials or other PIE communications. Instead, the information presented in PIE communications must be factual, objective, and unbiased; no characterizations, conclusions, or claims about an unapproved product or indication may be made or implied.^1,2 Therefore, PIE communications cannot state or imply that a new product or a new indication of an approved product fulfills a current unmet need. However, factual comparisons relating to endpoints and statistics can be made in PIE communications, and the FDA guidance provides examples that highlight some of the differences between providing factual comparisons and making a claim, characterization, or conclusion about an unapproved product or unapproved indication.²

Finally, all PIE materials should include a clear statement that the new product or new indication is not approved by the FDA, and that the safety and effectiveness of the new product or new indication has not been established.^1,2

How Can PIE Be Communicated?

There are several ways in which PIE can be communicated. Pre-approval AMCP dossiers and PIE slide decks are two of the most common. Other options for communicating PIE include:

Response letters to medical information requests³
AMCP PIE webinars³
Press releases
Brochures that describe a product or clinical trial
Flashcards that describe a clinical trial³
Links to ClinicalTrials.gov
Conference abstracts, posters, and oral presentations
Published manuscripts and study protocols

The FDA guidance does not address who can or should deliver PIE to HCDMs.² Therefore, any representative from the manufacturer can deliver PIE to an HCDM or other appropriate payer audience.³ In general, the field team of the manufacturer delivers PIE materials and communicates them to HCDMs, usually during an in-person discussion or a webinar.³ One common example is the medical science liaison, but other team members including account managers, account executives, field medical team members, and health economics/outcomes research liaisons can also communicate PIE materials.³ During and after the communication, payers can provide feedback and ask questions.

While the FDA does not give specific recommendations regarding exactly when PIE can be communicated prior to approval,² it is normally communicated 6 to 24 months prior to the anticipated product approval date.¹

Learnings From the Past Year

More and more manufacturers have developed internal processes (e.g., review by medical, legal, and regulatory teams) for reviewing and approving PIE materials. While some parts of the process, such as the desire to use publicly available information in PIE communications, are consistent across manufacturers, each manufacturer also seems to have its own unique methods built into their approach.

One common conversation that has occurred during the past year centers around the belief that pre-approval AMCP dossiers cannot be shared proactively. That is not the case. While post-approval AMCP dossiers (i.e., Approved Product Dossiers) can only be provided in response to an unsolicited request (i.e., reactively), pre-approval AMCP dossiers may be provided by the manufacturer in either a proactive or reactive fashion.¹

While many manufacturers choose to provide pre-approval AMCP dossiers reactively instead of proactively, that is starting to change. Indeed, some manufacturers have decided to share pre-approval AMCP dossiers proactively, sometimes as a follow-up after a PIE engagement (e.g., an in-person discussion or a webinar). If a manufacturer does not wish to provide a pre-approval AMCP dossier proactively, there are several other PIE materials that they can share with HCDMs in a proactive manner. These materials often contain information that is similar to the information contained within pre-approval AMCP dossiers. Finally, some manufacturers have started to use a mixed approach, depending on the specific product, where they share pre-approval dossiers proactively for some products and reactively for other products.

Finally, while most manufactures have ultimately been reluctant to share information on product pricing, it has been a topic of frequent discussion. For example, there have been discussions about whether to share information about potential cost offsets provided by a product (e.g., decreased length of hospital stay) prior to FDA approval. At this time, it is not clear if there will be a future increase in the sharing of information related to product pricing in PIE communications. However, the current perspective may change as manufacturers become more comfortable with PIE and incorporate it more routinely into their market access strategy.

Conclusion

Just a couple of years ago, many manufacturers were hesitant to develop and share PIE materials. However, even though PIE materials are not required,^1,2 many have found that they are useful tools for facilitating communications with HCDMs. Since it is possible that sharing PIE could benefit many new products and indications, we recommend that manufacturers consider the available options and think about the approach that aligns best with their strategy.

References

Academy of Managed Care Pharmacy. The AMCP Format for Formulary Submissions (version 4.1). Guidance on Submission of Pre-approval and Post-approval Clinical and Economic Information and Evidence. December 23, 2019. Available at: https://www.amcp.org/sites/default/files/2019-12/AMCP_Format%204.1_1219_final.pdf. Accessed March 2, 2021.
US Food and Drug Administration. Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities — Questions and Answers Guidance for Industry and Review Staff. June 2018. Available at: https://www.fda.gov/media/102683/download. Accessed March 2, 2021.
Academy of Managed Care Pharmacy. Pre-Approval Information Exchange (PIE): Implementing pre-approval communication strategies. November 17+19, 2020. Available at: https://www.amcp.org/sites/default/files/2020-09/CTVirtual_XCENDA_09_16.pdf. Accessed March 2, 2021.