The FDA recently issued a framework that provides important guidance on its thought process and rationale for ongoing efforts to embrace and encourage the use of real-world data (RWD) across the drug approval and safety surveillance continuum.
By Jeff Trotter, M.B.A
Introduced with comments from FDA Commissioner Scott Gottlieb, the framework reflects growing comfort and enlightenment associated with the use of real-world data in establishing real-world evidence (RWE) across the drug development continuum.
In recognition of the limitations of traditional clinical trials for supporting medical decision-making and in the interest of improving the efficiency of the drug approval process through the 21st Century Cures Act, the FDA has strongly advocated for the evaluation of a broad array of data gleaned from a variety of sources. Aside from data residing in electronic medical records, claims databases, and wearables – in other words, data compiled through processes geared toward day-to-day physician and patient-centric interactions in the real-world – the FDA is also interested in the value of observational research that either prospectively creates new RWD or retrospectively repurposes existing data for analytical purposes.
Here are some quick takeaways from the framework, addressing multiple perspectives and implications:
- Purpose continues to be the starting point – In and of itself, the framework suggests the continued acceptance of RWD as a mechanism for challenging the traditional gold standard for drug approval – the randomized double-blind controlled clinical trial. If, however, your purpose in utilizing or creating data is to establish evidence of real-world value (clinical, economic, humanistic) in informing and influencing other stakeholders (payers, in particular), the framework is of limited use (other than, perhaps, improving interactions with clinical operations professionals relating to the use of RWD).
- Clinical trials can be more cost-efficient – Particularly in rare diseases and oncology, the FDA has already expressed its comfort in single-arm study designs that utilize RWD as an external control arm. The framework outlines the process by which the FDA will continue to increase its confidence in nontraditional trial designs that accommodate RWD (provided it doesn’t compromise accepted standards for quality and epidemiologic integrity). As a result, through both the use of existing data and creative trial design, the drug approval process can be more operationally cost-efficient. Sponsors and CROs can now push the envelope and expect the drug approval process to be more expedient and less costly (and less intrusive to sites and subjects).
- Observational research is “good enough” – The framework establishes a pathway for data from prospective observational studies to support approval for expanded labeling and indications. This reflects an evolved and enlightened shift from the past in which observational studies were not considered sufficiently robust, either due to uncertainty over study design, execution, epidemiology or other factors. While underscoring the importance of transparency in all these factors, the FDA acknowledges that, with advanced statistical techniques, data collected reflecting real-world conditions provides the essential context necessary to consider the merits of actual use and outcomes. However (and appropriately) the framework affirms the FDA’s concern over the “cherry picking” that can result from multiple analyses from retrospective observational datasets.
- Maximizing the value of RWD – Much of the FDA’s new level of comfort in real-world data seems to stem from the experience gained from use of the Sentinal database specifically for post-approval drug safety surveillance. Accordingly, the framework continues to emphasize the value of RWD for such purposes. To that end, sponsors should look to optimize any required post-approval safety mandate by incorporating other measures that may be of more relevance to other (non-regulatory) stakeholders. Operationalizing such multiple uses, however, requires a more liberated organizational response. Specifically, this may be in the form of:
- Advanced training for clinical operations professionals – Clearly, much of the framework expresses evolving comfort for data, designs, and methods that may challenge traditional views held and operational algorithms employed. Organizations must endeavor to provide opportunities to shift expectations and skill sets to leverage the benefits of RWD.
- RWE Centers of Excellence – Sponsors are advised to establish multidisciplinary Centers of Excellence staffed by specialists and serving all sectors of a pharmaceutical company (including clinical, epidemiology, medical affairs, health economics, and commercial). At the very least, these centers will provide unique support to their organizations and avoid duplication in access to external databases and/or in the generation of de novo data through observational studies and registries.
I have been involved in observational research and registries for over a decade – always focused on their strategic benefit and, importantly, their limitations – and it is heartening to finally see the validation coming from the FDA. This should provide greater opportunities for our clients to embrace technology and to collaborate internally and, in so doing, to improve strategic and operational efficiency. And with encouragement from the FDA, to ultimately see that medical innovations continue to benefit patients as quickly as possible.
