Off-Label Promotion: The Transition from Volume to Value

Last week, FDA and Amarin Corporation reached a negotiated settlement of a legal case concerning off-label promotion for use of a drug for an unapproved indication. The negotiation established parameters for how Amarin and the FDA will operationalize the Court’s finding that the FDA cannot stop a company from providing truthful and non-misleading information about unapproved new indications of a drug. What the Court decision and the negotiated settlement mean for the future of off-label new use promotion beyond Amarin will become clear over time.

What this case prompts for me is perhaps the bigger question – and that is, how should FDA and life science companies consider the larger set of data issues that sit at the heart of our healthcare system’s transition from volume to value?

At a time when stakeholders are in furious search for value and the life sciences industry is hobbled in its ability to respond and demonstrate value in terms that are important for stakeholders, new approaches are needed to gain important information.

Consider that off-label promotion can apply to all sorts of information that has nothing to do with use of a drug for an unapproved indication. Off-label” promotion in its broadest construction applies to any information about a product that FDA did not agree to include in the product label – even information pertaining to approved indications. This type of ‘off-label’ information might demonstrate how the dosing improves patient adherence, or how the product addresses important patient risk/benefit preferences typically using real world evidence.

There are a myriad of different data points and information needed by different stakeholders in the pharma market, much of which is beyond the label in our current environment. This disjunction results from the fact that this type of real world information about effectiveness is often not amenable to randomized clinical trial study designed to demonstrate efficacy.

Given the pace of innovation in today’s pharma market — thanks to exponential growth in scientific knowledge — companies are increasingly hard-pressed to wait for years after market approval to develop the data that payers want in order to make coverage decisions. And even then, there is uncertainty about what would be acceptable to the FDA.

This issue is becoming vital. A recent study by Deloitte showed that return on R&D investment is half of what it was four or five years ago. Part of the decline in returns is surely due to the inherent difficulty in getting coverage and uptake when all the data everyone wants have to be developed post market. Further, the Sponsor may not be motivated to develop those data due to potential for FDA to disallow it.

There are signs, however, that FDA is increasingly aware of most of these issues. The agency has recently provided public demonstration of its consideration of non-sponsor stakeholder data needs:

  • It was recently announced that the Sentinel system will be used for real world effectiveness studies in addition to its core mission of looking for safety signals.
  • The FDA announced a new partnership with the Patient Centered Outcomes Research Institute to find ways to use the claims and electronic health record distributed datasets of each organization to develop powerful observational research tools. The project is nascent and will take quite a while to become operational.
  • The FDA just published a notice (2/24/2016) inviting payers to attend pre-submission meetings with willing device makers so that FDA and the Sponsor could learn about what type of data payers might want about a particular product.
  • FDA has initiated stakeholder consultations with patients to gain an understanding of what clinical results are important to patients in different therapeutic areas.
  • The PDUFA VI negotiations between the industry and FDA seem to have agreed that FDA will study applicability of real world evidence in approval and marketing.

Additionally, Duke University Duke-Margolis Center for Health Policy, led by former FDA Commissioner Mark McClellan, is in the process of leading several concurrent policy discussions on real world evidence and the FDA processes. The Center recently published a white paper – Policy Options for Off-Label Communications: Supporting Better Information, Better Evidence, and Better Care (Feb 2016). Earlier this month (March 2016), the Center together with the FDA, hosted a public meeting about the possibilities of using real world evidence for regulatory decision making.

In addition to these policy-related activities, it is important to note that the new FDA Commissioner, Robert Califf, has a deep background in health services research and translational science as a member of the PCORI Board of Governors. It would appear that FDA may be poised to move forward on many of these important data issues during his tenure.

The Amarin settlement still needs Court review and approval. But the fact that this settlement has occurred at all demonstrates how quickly and substantially changes are occurring in today’s healthcare marketplace — including challenges to areas as sacrosanct as off-label promotion.

Given the clear demand for information that is important to a diverse group of stakeholders including patients, physicians, payers and others, it would be prudent for life sciences companies to plan ahead in a systematic way. Sponsors should look at their pipelines and consider how they can conduct pre-market studies and gather data that are truly meaningful to stakeholders. This practice would also be a win for pharmaceutical companies since it could ultimately facilitate a more successful and effective market entry.



Jane Horvath, MHSA leads 3D’s Market Access and Reimbursement communications team with nearly 25 years of experience in health policy and reimbursement issues. Prior to joining 3D, Jane was the Executive Director of Health Policy and Reimbursement at Merck where she identified the business implications of state and federal policy developments. Jane has also worked in academia and has held a series of high profile government positions. Connect with Jane on LinkedIn.