Client challenge

A pharmaceutical company was conducting a single-arm trial to evaluate a treatment for an ultra-rare disease. In this type of trial, all patients receive the investigational treatment, with no internal control group. To support regulatory submission, the client needed comparative data to assess the treatment effectiveness. However, running a randomized control trial (RCT) was not feasible due to the extremely limited patient population and specific ethical concerns. To overcome this, the client engaged with P95 to design a real-world evidence solution. Using existing data sources, we developed an external control arm to serve as a reliable comparator for regulatory evaluation.

Our solution

P95 provided real-world evidence expertise for this complex clinical trial design by developing a robust external comparator for the single-arm trial. Our approach combined two components:

• Systematic Literature Review and Meta-Analysis: We performed a systematic literature review and meta-analysis, including 61 studies covering more than 2,200 patients across two geographic regions, to evaluate the same set of clinical outcomes used in the single-arm trial. We used Medline and Embase as literature databases and carefully stratified the collected data by treatment and important risk factors. This allowed us to generate a meaningful comparison to the trial population.
• Assessment of Rare Disease Data Sources: We also identified and reviewed 3 rare disease databases to assess their potential for supporting external comparison. This step helped to inform future possibilities for complementary data use in similar research contexts.

Together, these activities ensured a rigorous and fit-for-purpose external control arm tailored to the client’s regulatory needs.

Our Impact

• We successfully performed a detailed systematic literature review and meta-analysis, including 61 peer-reviewed studies with data from over 2,200 patients across 2 geographic regions. This formed a comprehensive report on the treatment and complications of patients with this ultra-rare disease.
• The results were delivered in time to be used for regulatory submission, and the regulatory review is currently ongoing.
• Our robust methodological and operational support ensured that the study remained on track and within the projected budget.

P95’s ability to apply real-world evidence expertise in complex trial settings, such as ultra-rare diseases, demonstrates our capacity to support data-driven decision-making where conventional trial designs are not feasible.

Contact us today to learn how our real-world evidence expertise for complex clinical trial designs can support your next submission.

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