New Industry Models: The Blurring Lines Between Drug Safety, Regulation, and Access

April 16, 2012
Drug Safety Directions

Applied Clinical Trials

I begin this article exactly where I left off in my previous one–a quotation that “99% of future predictions will fall short of the necessary unreasonableness for a correct prediction,” for I wish to discuss another subtle trend that appears ever more plausible each passing year. When drug regulation began, its mission was to assure efficacy and quality, whereas food regulation primarily focused on safety. In time and as we learnt about adverse events, regulation became about all three, and establishing enough data to achieve approval and access. After decades of this regulatory model in balance, many long held precepts have evolved significantly over the past decade.

Safety has emerged as perhaps the core beacon guiding regulatory action and oversight today. It is well accepted that approval is in fact based on “a point in time” and our knowledge evolves over a lifetime–leading to expanded or restricted indications. A clear fourth hurdle has emerged as the true arbiter of access–reimbursement—based not only on regulatory approval (absolute effectiveness) but on principles of “value,” comparative (cost) benefit profile that includes both efficacy and safety. What appeared unreasonable only a few years ago, regulatory approval itself rooted in comparative benefit, now appears plausible. In other words, the lines between safety, regulation and access are progressively getting blurred.

In this milieu, the role of “safety” within a biopharmaceutical organization is rapidly evolving, and many facets of that evolution may be explored in successive posting. However, it is not my premise that drug safety reporting stands on the cusp of a major shift; what I believe is that the science of safety and comparative safety profiles, and models of risk management stand to penetrate ever deeper into the lifecycles of development and commercialization. One emerging case study of this shift appears to be the Sentinel project (Pink Sheet, Jan 23, 2012). It was always a possibility that Sentinel, once operational, may far extend the use of data collected for safety surveillance.

To a degree, FDAAA of 2007 and its overarching mission to improve drug safety provided funding for opening the gates to the house using a key marked ‘safety’; once open however, agencies and other parties can collectively wander into any room we want. These already, speculatively, include understanding real world usage of medicines and real world effectiveness, comparative effectiveness research, off-label usage analysis for pharmacovigilance purposes, head-to-head observational studies, and open phase-IV observational trials. In other words, a veritable field of dreams–if you build it, they will come! Sentinel could be the ideal laboratory for the agency to independently test the effectiveness of various risk minimization measures imposed on the industry. Of course, it remains to be validated whether the data collected in Sentinel has sufficient quality and fit for this purpose. But irrespective of Sentinel, similar analyses is being conducted, for instance by payors. For example, Medco’s head-to-head observations study (plavix/effient) to not only compare effectiveness, but to also collect information on HCP actions takes based on risk minimization measures. Interested parties across the pond are putting forward similar ideas around the eventual use of Eudravigilance data, post it full implementation by circa 2015.

As industry, we ought to accelerate discussion into what this means regulatory and safety capabilities within our own boundaries and what strategic changes are required for a scenario where safety, regulatory and commercial access/use are increasingly harder to tease apart.

Written by Sanket Agrawal, Global Regulatory Affairs and Safety, Amgen Inc., for Drug Safety Directions.


The Pink Sheet, Jan. 23, 2012, "Mini Sentinel Data Covers 126 Million Patients; FDA Weighing Potential Uses For Drug Industry."