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Strengthening regulatory submissions for innovative treatments using RWE

The focus on real world evidence (RWE) and its potential to support regulatory decision-making has gained global traction.

Regulatory bodies, such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), have released their expectations for the use of real world data (RWD) and RWE. In July 2022, the International Coalition of Medicines Regulatory Authorities (ICMRA) published a statement calling for increased international collaboration on the use of RWE.

This marks an exciting time in the pharmaceutical space to advance innovative treatment development, but it also brings unique challenges.”

This marks an exciting time in the pharmaceutical space to advance innovative treatment development, but it also brings unique challenges. The regulatory landscape is rapidly evolving, with major regulatory bodies releasing guidance documents for the use of RWD. Regulators, such as EMA and FDA, are providing industry with guidance documents and frameworks to promote data quality and management, expectations for fit-for-purpose RWD, and increasing diversity in clinical trials.

How RWE can increase representativeness in research

While traditional randomized clinical trials (RCTs) remain the gold standard for drug development research, the restrictive eligibility criteria for participation tend to exclude real world patient populations. In 2022, the FDA released a draft guidance which reiterated and reinforced their expectations that sponsors enroll participants in clinical trials who reflect the demographics of relevant populations with regard to age, gender, race and ethnicity.

RWD can be used to inform recruitment strategies to address the expectations of the FDA. RWE studies, of subpopulations of interest, may complement the data generated from RCTs, as a means to achieve these goals.

Considerations for RWE: The importance of knowing your data and methods

RWE is increasingly being used across the product lifecycle to address unmet needs, accelerate and optimize clinical trials, for approval or label expansion, for health technology assessments (HTA) submissions to accelerate/improve access, to demonstrate value and differentiation in post-approval, and to optimize care pathways. When RWE is being used for regulatory purposes, the RWD must be fit-for-purpose, the design used to generate RWE needs to provide adequate scientific evidence to answer or help answer the regulatory question, and the study conduct must meet the regulatory requirements.

There are three criteria when utilizing RWE for regulatory decision-making.

1. The first is understanding whether the data are fit-for-purpose. There is no one-size-fits-all approach for the use of RWE. The assessment requires understanding the provenance, access, and curation of the data and fit-for-purpose data feasibility needs to occur early in study planning. When multiple sources of data are needed to gain insights into the complete patient journey, careful planning is essential.

2. In addition to data fitness, the study must be designed to provide adequate scientific evidence to answer or help answer the regulatory question (e.g., has the study been designed to minimize bias and confounding and are appropriate analytic methods planned).

3. Finally, the conduct of the study must meet the FDA regulatory requirements.

Design options such as an innovative extension study can be used to follow patients over a long period of time after they have completed a clinical trial, where the real world follow-up needs to capture relevant endpoints collected from site-based primary data collection, existing data sources or using direct-to-patient methods. If using RWD as an external comparator for a single-arm trial (SAT), the patients in the external control cohort mirror the inclusion and exclusion criteria for the SAT and trial outcomes are examined in the RWD external control cohort. A pragmatic randomized trial assesses real world effectiveness, safety, and and/or health economic benefits in routine practice. When designed and executed appropriately, these real-world approaches can be used for regulatory decision-making.

2023 and beyond

The use of RWE for regulatory decision-making is not new. It has long been accepted in the post-marketing setting and to a limited extent in pre-market circumstances. Today, around the globe, the use of RWE for regulatory decision making is expanding to support regulatory decisions for the efficacy of therapeutic products. RWE can be used earlier in clinical development and innovative designs and approaches can be employed.

RWE can be used earlier in clinical development and innovative designs and approaches can be employed.”

This marks an exciting time in clinical research and invites more opportunities for therapeutic innovation. In some cases, this can mean accelerating treatment development, and or availability, for more broad and inclusive patient populations.

Text by Jaclyn Bosco, VP & Global Head, Epidemiology, Real World Solutions, IQVIA, and Marni Hall, VP & Global Head, Regulatory Science & Strategy, Real World Solutions, IQVIA

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