Authored by Rare Disease Compliance Consortium (RDCC) 1 & Professional Patient Advocates in Life Sciences (PPALS) 2
In a prior article in Healthcare Business Today, we explored the lived experience of individuals affected by rare diseases and the critical role that Patient Advocacy Organization (PAO) leaders and patient advocates play in navigating that journey.3 We emphasized that these leaders are not passive recipients of information, but rather are deeply engaged, highly informed participants in care, research, and community support.
What has become increasingly clear since then is that the regulatory framework governing how pharmaceutical companies communicate with these PAO leaders has not kept pace with their evolving role.
i. The Problem: A System Built for a Different Era
Rare disease patients often wait years—sometimes decades—for an accurate diagnosis. During that time, families face uncertainty, misdiagnosis, and, in many cases, irreversible disease progression.4 In this fragmented landscape, PAO leaders serve as essential guides. They connect patients to specialists, interpret complex scientific developments, and help families understand emerging treatment options.
Yet under current FDA regulatory frameworks, these leaders are typically treated no differently than the general public when it comes to pharmaceutical communications. While companies can share detailed scientific information with healthcare professionals, communications with PAO leaders are treated the same as communications with regular patients: as direct-to-consumer (DTC) promotion.
That classification creates a problem. While PAO leaders are not licensed clinicians, they possess deep scientific literacy, regularly engage with researchers and regulators, and play institutional roles within structured organizations. Limiting their access to up-to-date scientific information from companies limits the valuable role they play in the healthcare ecosystem and their ability to support patients.
ii. The Result: A “Grey Zone” That Chills Communication
This mismatch has created a regulatory grey zone. Companies can and do share general disease awareness information with PAO leaders. But when discussions turn to real world evidence about specific products—even when the information is on-label or consistent-with-label and presented in a non-promotional manner—legal and compliance teams often proceed cautiously or avoid the conversation altogether. This caution is even greater for off-label information, even though the FDA has produced a guidance for the sharing of such information with physicians (SIUU Guidance)5 and even though that guidance could be equally applied to off-label communications with PAO leaders.6
The issue is not that such communication is clearly prohibited. It’s that the rules are unclear as applied to PAO leaders. In highly regulated industries, ambiguity tends to produce conservatism. When the boundaries are not well-defined, companies default to risk avoidance. Over time, this leads to a chilling effect where even lawful, responsible, and potentially beneficial scientific exchange does not occur.
For rare disease patients, that gap matters. When trusted intermediaries lack access to timely, high-quality scientific context, the flow of accurate information to patient communities slows down.
iii. Why This Matters More in Rare Disease
In more common conditions, patients can rely on a broad network of specialists and widely available clinical knowledge. Rare diseases are different. There may be only a handful of experts worldwide. Frontline clinicians may encounter a condition once in their careers, if at all. As a result, patients and caregivers often rely heavily on PAO leaders to interpret emerging science and guide next steps.
These leaders are not simply advocates; they are translators of complex information and connectors within a highly specialized system. Limiting their access to scientifically grounded dialogue does not eliminate information flow, it redirects it. In the absence of structured engagement with manufacturers, patients often turn to informal online networks, where the quality and accuracy of information can vary widely.
iv. What the Law Actually Allows
Importantly, existing law may be more permissive than many assume. Over the past decade, U.S. courts have consistently held that truthful, non-misleading scientific speech by pharmaceutical companies is protected under the First Amendment.7 These protections do not hinge on whether the audience is a licensed physician. Instead, they focus on the nature of the communication itself.
At the same time, FDA guidance has already evolved in certain areas. For example, the agency permits manufacturers to share complex scientific and economic information with payors—entities that, like PAO leaders, are not clinicians but possess the expertise to evaluate such data responsibly.8 This raises a natural question: if sophisticated, non-clinical stakeholders can receive detailed scientific information in one context, why not in another?
v. A Practical Path Forward: Structured, Safeguarded Engagement
The answer is not deregulation, it is clarification. A workable path forward would recognize that certain PAO leaders function as expert intermediaries and allow carefully bounded scientific dialogue with them under clear safeguards.
Until such guidance is available, manufacturers can take steps to safeguard their communications with PAO leaders by, for example:
- Using balanced, non-misleading, and evidence-based materials
- Ensuring a clear educational (not promotional) purpose
- Limiting the PAO audience to those with sufficient seniority and scientific literacy (e.g., PAO senior leaders and scientific advisory board members, if applicable)
- Limiting the cadence to how often information is shared
- Limiting discussions to on-label or consistent-with-label information
- Following FDA’s SIUU Guidance when communicating off-label information, and/or only providing such information in response to an unsolicited request
- Documenting interactions through established compliance processes
Equally important are safeguards that PAO’s may consider to reduce regulatory risk, such as:
- Internal review of scientific information
- Ensuring communications to members reflect balanced, independently validated information rather than sponsor-driven messaging
- Transparency around relationships with industry
Many PAOs already have governance frameworks, conflict-of-interest policies, and scientific advisory structures in place. Building on these systems would allow engagement without compromising independence.
vi. Closing the Gap
At its core, this is not about expanding promotion, it is about improving the flow of accurate, contextualized scientific information within a highly specialized and underserved area of medicine. The current binary framework—healthcare professional versus general public—no longer reflects the realities of the rare disease ecosystem. PAO leaders occupy a middle ground that the law has yet to clearly define.
Clarifying their regulatory status would not weaken patient protections. Done correctly, it would strengthen them by ensuring that trusted community leaders have access to the information they need to support informed, evidence-based conversations.
In rare disease, time matters. Delays in diagnosis, treatment, or understanding can have irreversible consequences. Bridging the communication gap between scientific innovation and patient communities is not just a regulatory question, it is a practical and ethical one that needs to be solved without further delay.
1) Patrik Florencio (Chief Risk, Ethics, & Compliance Officer, Amicus Therapeutics), Jill Dailey (VP & Chief Compliance Officer, Oncology, Menarini Stemline), Gary Giampetruzzi (Partner, Paul Hastings LLP), Jason Russell (Associate, Paul Hastings LLP), Eric Rogers (VP, Ethics & Compliance, Alexion Pharmaceuticals), Sarah Whipple (VP & Global Chief Compliance Officer, Apellis Pharmaceuticals), Sheila Abraham (VP & Chief Compliance Officer, Dompe U.S.), Piyush Sharma (Chief Ethics & Compliance Officer, Alnylam Pharmaceuticals), Michael Hercz (SVP, General Counsel & Chief Compliance Officer, Sentynl), Ben Ehrhart (SVP, Compliance & International Legal, Ultragenyx), Donna White (VP Compliance, Chiesi USA), Chad Morin (Chief Compliance Officer, Viridian Therapeutics), Tara D’orsi (EVP, General Counsel & CCO, Kyowa Kirin), Lori Alarimo (Deputy Healthcare Compliance Officer, Genentech), Jaimee Reid (Head of compliance & Privacy Officer, Intercept Pharmaceuticals), Melissa Gothie (SVP, Chief Compliance & Risk Officer, PTC), Linda Hellstrom (Head of Global Compliance, Agios Pharmaceuticals).
2) Jayne Gershkowitz (Co-Founder, PPALS); Jean Campbell (Co-Founder, PPALS); Barbara Wuebbels (Co-Founder, PPALS).
3) Alarimo et al., Experience of Affected Individuals: Compliance in the Rare Disease Space, July 24, Healthcare Business Today (2024).
4) J. Benito-Lozano et al., Diagnostic Delay in Rare Diseases: Data From the Spanish Rare Diseases Patient Registry, 7 Orphanet J. Rare Dis. 418 (2022); C. Phillips et al., Time to Diagnosis for a Rare Disease: Managing Medical Uncertainty. A Qualitative Study, 19 Orphanet J. Rare Dis. 297 (2024).
5) U.S. Food and Drug Administration. Scientific Information on Unapproved Uses of Approved or Cleared Medical Products: Guidance for Industry and FDA Staff. Silver Spring, MD: U.S. Department of Health and Human Services, January 2025. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/communications-firms-health-care-providers-regarding-scientific-information-unapproved-uses.
6) Please note that the sharing of investigational drug information with PAO leaders and their scientific advisory boards prior to FDA approval is not included in this discussion as it will be the subject of a forthcoming article.
7) United States v. Caronia, 703 F.3d 149 (2d Cir. 2012); Amarin Pharma, Inc. v. FDA, 119 F. Supp. 3d 196 (S.D.N.Y. 2015); Pacira Pharm., Inc. v. FDA, No. 15 Civ. 7055 (S.D.N.Y. Dec. 15, 2015).
8) U.S. Food & Drug Admin., Drug and Device Manufacturer Communications With Payors, Formulary Committees, and Similar Entities – Questions and Answers: Guidance for Industry and Review Staff (June 2018), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-and-device-manufacturer-communications-payors-formulary-committees-and-similar-entities.
