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Real-world evidence (RWE) has evolved from a promising concept into a central component of regulatory decision-making1,2. Today, global health authorities rely on RWE to understand how therapies perform in real clinical settings beyond the controlled environments of randomized trials. But here’s the problem: while everyone agrees RWE is valuable, no one can agree on the rules.
For organizations developing treatments across multiple regions, this lack of consistency creates real obstacles. Without clear, harmonized feasibility criteria, global RWE programs face increased uncertainty, higher operational costs, and in some cases, feasibility assessments that fail before a study begins. Understanding these regulatory gaps isn’t just an academic exercise—it’s fundamental to ensuring study success.
Across the world, regulators are actively developing RWE regulatory frameworks to define how RWE should be generated, validated, and applied. The U.S. FDA has led with extensive guidance documents, followed by the EMA’s structured frameworks and growing contributions from agencies across Asia, Latin America, and other regions1,3.
Despite this momentum, alignment remains limited. A recent analysis found that only four regulators globally have agreed on common terminology for what makes RWE “fit for use”7. In practice, this means that sponsors running multi-country programs must navigate a patchwork of expectations, where each regulator interprets data quality and fitness differently.
Before investing in an RWE study, sponsors must confirm whether the available data can meaningfully address their regulatory question. A feasibility assessment examines whether data sources exist, if they meet quality thresholds, and whether they sufficiently capture the required endpoints.
The problem? Regulators prioritize different elements, and most guidance lacks the operational detail needed to make confident decisions. As a result, about one-third of proposed RWE studies are deemed infeasible—often not because the data doesn’t exist, but because the criteria for assessing feasibility are unclear or inconsistent3.
Every agency emphasizes data quality, yet few define what that entails. Questions such as acceptable levels of missing data, validation standards, and documentation of data provenance remain largely unanswered. Variability across regions often pushes sponsors to build to the strictest standard, driving up both cost and complexity.
Most guidance agrees that real-world evidence must be “fit for purpose,” meaning it’s both relevant and reliable for the study question. However, the interpretation differs. The FDA emphasizes reliability and relevance, while the EMA uses distinct terminology and criteria. For sponsors, structuring an assessment that satisfies multiple agencies remains an ongoing challenge 4.
Even practical aspects like what to include in regulatory submissions differ significantly. Requirements for data source documentation, analytical transparency, and sensitivity analyses vary by region. This often forces sponsors to prepare separate submission packages for the same study, increasing workload and delaying review timelines5.
RWE study design offer more flexibility than traditional clinical trials, but that flexibility introduces ambiguity. Regulatory guidance varies in areas such as acceptable study designs, comparator selection, confounding control, and endpoint definitions.
This variability makes it really hard to design a study with confidence that regulators in multiple countries will accept it.
These aren’t just theoretical problems. They have real consequences:
Global harmonization will take time, but sponsors can mitigate risk and improve feasibility outcomes by taking proactive steps:
Encouragingly, the regulatory landscape is moving in the right direction. The regulatory community knows these gaps exist and is working on fixing them. There are international efforts underway to align terminology, standardize feasibility assessments, and create more consistent expectations for RWE submissions6. Until those efforts mature, success in RWE will depend on strategic foresight—careful planning, strong data infrastructure, and deep regional awareness.
Organizations that invest in understanding these feasibility gaps today will be better positioned to execute globally acceptable studies tomorrow. In an era where real-world data increasingly shapes regulatory and market decisions, mastering this complexity is no longer optional—it’s a strategic imperative.
About Maxis Clinical Sciences: Maxis Clinical Sciences supports sponsors in navigating the evolving global RWE landscape. Our experts provide end-to-end guidance on study design, feasibility assessment, and regulatory submissions to help ensure real-world data meets regulatory expectations across regions.
