In recent years, within the United States and Europe, we have witnessed the growing utilization of real-world evidence (RWE) in drug approval submissions at both the regulatory and payer levels incorporated in awareness campaigns, disease education, and even in policymaking in some markets. For rare and ultra-rare diseases specifically, the use of real-world data (RWD) and RWE by life sciences companies can help address the unique challenges during the patient-focused drug development process, conceptualize and supplement traditional randomized controlled trials (RCTs), and inform regulatory and/or payer decision making.

Although the practical applications of RWD/RWE differ between the United States and Europe, and the use of such evidence in the rare and ultra-rare disease category has methodological shortcomings, different approaches can be utilized to overcome these limitations and successfully optimize the robustness of outputs and relevance for key decision-makers in those regions.

Randomized controlled trials (RCTs) remain the gold standard for assessing treatment efficacy and safety, serving as the foundation for drug approval in most diseases. However, RCTs are expensive, time-consuming, and often are either placebo-controlled or use active comparators that do not reflect clinical practice. In rare and especially ultra-rare diseases, conducting RCTs may be either unethical due to control arm requirements or not feasible because of tiny patient populations that are geographically dispersed across the globe.

Recognizing these limitations, regulators and payers are increasingly more receptive to incorporating RWE into their decision-making processes. This creates opportunities for life sciences companies to collaborate with patient advocacy groups on generating RWD/RWE and utilizing it in awareness campaigns, disease education, and in advocating for policy changes that could promote not only earlier product commercialization but also patient access.