Legal rulings have pushed off-label promotion into the realm of possibility for pharma, but guidelines are still non-existent and legal ramifications still punitive for those that get it wrong. Bio and PhRMA have weighed in to offer some guiding principles to help the industry walk the perilous path, but ambiguity persists, as does risk to both pharma companies and individuals.
How Did We Get Here?
Recent legal rulings have seen First Amendment free speech rights trump the FDA on off-label promotion. Klick Health has been tracking these court rulings and potential implications in several prior posts. With that said, the conviction of two ex-Johnson & Johnson execs in late July, and the up to 10 years of prison time they each face, remains a reminder that off-label promotion is not all fair game. The tipping point for legal off-label promotion rests on the court’s interpretation of “truthful and non-misleading”. Though court rulings have defined these terms, these definitions are anchored into the specific cases at hand leaving the pharma and biotech communities wondering what truly is fair game.
Bio and PhRMA Step Up To The Plate
In an environment where the opportunity to inform patients and HCPs must be balanced with the real fear of penalty, the industry is desperately seeking guidance. Early legal rulings were narrow in scope but theoretically companies could have taken action and actively promoted off-label. Few, if any, did, with the reputational, financial, and potentially criminal risks understandably outweighing the benefits for most. As the industry waits for the FDA to provide guidance, Bio and PhRMA have released some exceptionally well-thought out principles that offer a balanced perspective of what “truthful and non-misleading” may look like in practice.
Responsible Sharing of Truthful and Non-Misleading Information
Bio and PhRMA outline nine key principles for off-label promotion that the industry would be well served to follow. It’s important to note that, likely purposefully, the words “off-label” or “promotion” do not appear at any point in the document or appendices. The document does however specifically note that the principles are not meant to guide activities that we would traditionally consider non-promotional medical educational activities. It also uses specific wording in the legal judgments surrounding off-label promotion of “truthful and non-misleading”. The exclusion of “off-label” and “promotion” indicate that even though the principles are sound, the industry should not interpret them as official guidance.
The nine principles align generally to two categories: (1) broad positions/values and (2) more specific principles that approach guidance. The document is worth reading in full here, especially as they give numerous scenarios to demonstrate how these principles would apply in real-world environments.
(Note that the groupings are my own and not from the original document, as such the numbers associated with the principles appear out of order.)
1. Commitment to Accurate, Science-Based Communications
Basically, if it’s not sound science we shouldn’t speak of it.
2. FDA-Approved Labeling is a Primary Source in Sharing Information with Health Care Professionals About Medicines
On-label promotion should be fair and balanced. One might interpret the wording of “a primary source” to indicate that there are other primary sources that are not on-label… but this principle does not speak directly or indirectly to any off-label promotion.
3. Additional Science-Based Information from Sources Other Than FDA-Approved Labeling Helps Health Care Professionals and Payers Make Informed Decisions for Patients
Sharing more information, when done responsibly, is beneficial to HCPs and payers, even when not on-label. The description outlines the types of information that this may include, and more importantly, explicitly states that contextual information and disclaimers are required to ensure shared information is truthful and non-misleading.
4. Science-based Information About Alternative Uses of Medicines Can Improve Health Care Decision-Making
Echoing principle #3, this states the importance of communicating truthful and non-misleading information to HCPs and outlines thoughts on providing supportive materials to ensure fair balance for “appropriately sophisticated” audiences.
5. Communicating with Payers About New Medicines and New Uses of Approved Medicines Facilitates Patient Access Upon Approval
Communication with payers in advance of a new drug or label update will benefit patients.
6. Real-World Evidence Based on Patient Experience and Pharmacoeconomic Information Can Improve Understanding of Health Outcomes and Costs
Promotion to HCPs of follow-up analysis including retrospective studies is beneficial. This principle and the accompanying scenario, are inclusive of company-led analyses that are not peer reviewed.
7. Commitment to Share Information Published in Scientific or Medical Journals
Companies should be able to share reprints of off-label studies with significant descriptive information, regardless of the study’s sponsor. Contrary to the topline title of the principle, it does not weigh in on any obligation to share studies regardless of study outcome.
More Specific Principles
These principles closely resemble early guidance to the “how” question.
8. Companies Should Provide Scientific Substantiation if Shared Information is Not Contained in FDA-Approved Labeling
This principle walks through a more robust set of suggestions to ensure off-label promotion is still fair and balanced. It specifically raises the bar on communicating study design, methodology, and statistical limitations of any studies that are not on-label. Additionally, there is an obligation to communicate any contradictory evidence to the information that is being presented.
9. Communications Should Be Tailored to the Sophistication of the Intended Audience
The depth of information/supporting information must match the sophistication of the intended audience (e.g., the HCP). This suggests the bar for truthful and non-misleading will vary depending who the intended HCP audience is.
So Where do Gaps Still Exist?
A number of unanswered questions still persist. Bio and PhRMA have laid out these principles as a starting point- but even these principles highlight some of the most important outstanding questions.
- If we allow the promotion of company-initiated and sponsored non-peer reviewed studies (principle 8), who is the gatekeeper to ensure studies are not for the sole reason of promotion or even that all study information is appropriately communicated publically?
- How do we ensure that company-led studies are designed in such a way that both negative and positive outcomes are possible (even if the study limitations are disclosed how do we eliminate bias in study design)?
- Does principle 9 extend to an actual commitment to share (or make available) all published papers regardless of whether the results are beneficial to brand promotional strategy? If not, how do we achieve fair balance if we only promote where off-label use appears beneficial?
- If truthful and non-misleading means ensuring our messages are always tailored to the sophistication of the intended audience, will companies be liable when they don’t take reasonable precautions to ensure other less sophisticated audiences don’t have access to those messages?
- Do similar rules apply to Direct to Consumer (DTC) marketing? If so, how do we tailor our messages to consumers when study design, methodology, and statistical significance are pivotal in ensuring statements are truthful and non-misleading? (Note that the principles discussed are designed solely for HCPs- DTC principles may be in the works.)
More broadly, what happens if industry self-regulation doesn’t work? Where truly does the line live between First Amendment free speech rights and the current laws limiting off-label promotion?
Do We Now Live in a World Where Off-Label Promotion Will Become Commonplace?
The short answer is not quite yet. Bio and PhRMA have done a commendable job at laying out some principles that take a large first step in industry self regulation, but enough uncertainty exists that off-label promotion is still an exception in the marketplace. In the mid to long term we should expect more clarity from the courts and the FDA. We will wait for a case that is appealed to the Supreme Court (note that there are currently no cases on their way to the Supreme Court yet) and that is broad enough to create a legal line in the sand. Only following this, or explicit FDA guidance, will off-label promotion become commonplace. Until then we will all be paying close attention to the courts, the FDA, and guidance from leading industry groups such as Bio and PhRMA.
Have additional concerns or questions? Mike is eager to continue the conversation!