The Medicines and Healthcare Products Regulatory Agency’s recent announcement about the new licensing pathway for innovative medicinal products, in force in the UK starting January 1, 2021, is full of potential and some challenges. The new scheme will consist of an “adaptive authorization pathway,” incorporating real-world evidence (RWE), continuous benefit/risk assessment, novel clinical trial design, and various regulatory flexibilities. This is the latest move by the regulator in seeking to align with the industry and promote new ways of facilitating innovation.
RWE has figured prominently as a very promising, yet underutilized, way to boost the development of innovative medicines. All stakeholders ranging from regulators and payers to industry, patients, and clinicians agree that more collaboration is needed to harness the true value of RWE. This was the main topic discussed in the first stakeholder meeting hosted by RWE4Decisions, titled “Realising the Potential of Real-World Evidence for Learning Healthcare Systems.”
Bringing to the market products aimed at treating very rare conditions and heterogeneous patient populations is rendered difficult when meaningful data collection remains elusive. RWE can address these evidentiary gaps and reduce uncertainties as well as support novel market access tools such as outcome-based agreements. However, the EU lacks a framework within which RWE can be fully and systematically used, and, from a reimbursement perspective, it remains a segmented landscape in which each national health technology assessment (HTA) agency can adopt a different approach as to the requirements for and interpretation of the available data on clinical effectiveness. Further, while there is a general willingness for increased patient engagement and patient-reported outcomes, there is no defined role for the patient in the approval and reimbursement procedures; instead one sees more of an ad hoc involvement relying on the proactivity of the players in each scenario.
The discussion among the panel members culminated in compelling proposals. The speakers expressed their frustration that while there has been a number of initiatives and pilots at the EU level, what we need is a concrete framework. More specifically:
- From the perspective of the regulators and assessors, RWE should provide good-quality data responding to a predefined question, which ideally should be set out in the protocol rather than guiding the questions we should be asking. Registries are a good method of data collection, but isolated company registries are much less usable than existing, disease-specific registries. The European Medicines Agency (EMA) representative requested concrete examples of successful RWE use, with reliable data sources and as representative as possible of the European regulation.
- The industry perspective, with the experience of two years since the EMA’s first approval of CAR-T therapies, is that of a segmented European landscape that creates inefficient data collection requirements. While national agencies welcome registries to support decisions of value access, the setting up and maintaining of various registries is burdensome, not only financially but also from an implementation point of view. A more collaborative approach, for example via an EU learning network, would help homogenize these requirements, noting there are already positive initiatives in Europe to advance the systemic use of RWE.
- The payer’s point of view, as expressed by a representative of the UK HTA authority, the National Institute for Health and Care Excellence (NICE), agrees with the initiative to increase the use of RWE in evaluating products and developing guidelines. It was emphasized that the role of the randomized clinical trial is not to be replaced but rather complemented by RWE. This has been used successfully in NICE’s economic models of diabetes and Parkinson’s and can further be used in instances where there is lack of evidence in respect of select patient groups. RWE can help the extrapolation of data beyond clinical trials.
- From the patients’ perspective, one of the remaining major challenges in the space of rare diseases is the high heterogeneity of the disease expression in different patients. An artificially homogeneous patient population satisfying the requirements of clinical trials does not represent the actual benefit of the treatment to the full patient population. In addition, the fact that each HTA agency requires different postapproval data hampers a conclusive data collection. From a patient advocate’s perspective, the unclear legal status of registries and the unclear legal framework about the value of observational studies undermine the position of the patient in the approval procedure.
Looking to the future and addressing the need for cooperation of the various stakeholders, it was also mentioned that the proposal for the Joint HTA Regulation could provide the forum to channel the results of the current ongoing initiatives, as it foresees a structured cooperation between EMA and HTA bodies prelaunch, at launch, and possibly postlaunch.
All speakers agreed that in order to maximize and optimize RWE, it is necessary to increase the existing collaboration and put in place a clearer framework as well as ensure that decision-making considers stakeholder input. Last, the panel highlighted the potential of artificial intelligence (AI) and digital tools in the collection and analysis of RWE; developing guidelines should therefore reflect the role of AI and its use in data collection.
In a timely update, the EMA has published a draft guideline subject to public consultation, aiming to optimize the use of registry-based studies to collect RWE. The guideline includes considerations regarding the quality and type of data, the feasibility and quality control measures around additional data collection, and it also provides direction about how the study protocol and the collection, quality management, analysis, and reporting of the data should be addressed. The final guideline is expected in 2021, and this is one of the many encouraging steps in addressing the use of RWE in the EU and the UK. It is encouraging to see key stakeholders get together, analyze the state of play with its challenges, and outline pragmatic ways forward.
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