Long before COVID-19, there was a growing acceptance of the importance of real-world evidence (RWE) in guiding decisions around the approval and access to novel interventions.
Part of this was driven by a need to better understand the true value of these interventions – to the patient, to the payor, and to the healthcare system. The efficacy and safety of an intervention, as shown in a Phase III clinical trial, is no longer sufficient to demonstrate value and guarantee access. However, part of this acceptance is also driven by the need to accelerate timelines to approval, and to find other strategies for generating evidence when Phase III data fails to provide the ‘slam dunk’.
Now, as we adjust to the era of COVID-19, RWE, and thus real-world research (RWR), has been pushed center stage, and industry, and the medical community as a whole, are turning to this research area for answers. Whether through large observational studies, or patient registries, in which patients are observed and data are captured over time, or by tapping into existing data sources to extract insights from electronic medical records (EMRs) or medical claim databases, RWR holds the potential to fill gaps in our understanding. First and foremost, RWR promises to shed light on COVID-19 itself, supporting the development of potential treatments and vaccines through a better understanding of the disease. Secondly, it allows us to capture the broader impact of COVID-19 on the management, and thus outcomes, of patients with other diseases and conditions, tracking how management practices are shifting and the consequences of these shifts. However, perhaps most importantly, RWR can help support and drive innovation in these challenging times, when clinical trial programs may have stalled, or produced only immature data, by filling gaps and strengthening the evidence base for a novel intervention.
Clinical trials remain the gold standard for demonstrating the efficacy and safety of novel interventions; however, the way in which we run clinical trials will need to evolve to fit the ‘new normal’, so regulators and health authorities’ needs can continue to be met. However, strategies can be deployed to minimize the burden of generating this needed clinical evidence. One such strategy is the use of single-arm studies (i.e. studies without a control arm, in which all patients receive the novel intervention), which are gaining traction with regulatory authorities. In a recent analysis of regulatory approvals by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), between 1999 and 2014, 15% of FDA applications and 11% of EMA applications were approved on the basis of single-arm studies.1
As with any new paradigm, single-arm studies have limitations that need to be balanced against their strengths. They can allow for quicker approval and reimbursement, remove the need for a comparator, require fewer patients and are logistically easier to implement. However, hesitancy remains among regulators and health authorities, because single-arm studies do not allow for benchmarking against standard of care (SoC), as well as possible bias, among other issues. This is where RWR can fill the gap. When single-arm studies are combined with RWR strategies, such as indirect treatment comparisons (i.e. a statistical comparison of different interventions from data stemming from separate studies) or the use of historical controls (i.e. using data from retrospective EMR or claims databases to provide data on SoC), they provide a richer evidence base and support a more convincing value narrative for regulators and health authorities.
This is just one example of how RWR can play a key role in the COVID-19 era. The cost savings associated with this type of approach means RWR has advantages that will endure beyond this current crisis, and therefore an increased reliance on RWR now may reshape the way in which novel interventions are evaluated in the future.
Are you interested in more information on the role RWE and RWD can play in your plans, and how best to use it in your communications strategies? We’re here to help.
1 Hatswell AJ, Baio G, Berlin JA, Irs A, Freemantle N. Regulatory approval of pharmaceuticals without a randomized controlled study: analysis of EMA and FDA approvals 1999-2014. BMJ Open. 2016;6(6):e011666.