OBJECTIVES

: Approximately fifty percent of all new drug launches in rare disease and oncology recently have involved single-arm trial product launch scenarios for products that are in fast-track regulatory programs. This is a significant departure from our traditional randomized-controlled trial (RCT) and conventional evidence hierarchy-based decision model and suggest that clinical trial models are changing, driven by technology and other advances. This analysis considers evidence requirement trends associated with single-arm development scenarios and lessons for improving future product value demonstration approaches.

METHODS

: We reviewed regulatory submissions and health technology assessments in North America and the EU5 for over 40 products launched in the past five years to evaluate how real-world evidence (RWE), patient-centric and other health outcomes have been used in supplement to single arm pivotal trial launch scenarios. Emphasis was placed on identifying common gaps in single arm launch scenario evidence packages, the nature and methodological rigor of gap-fill scenarios, and acceptance of these approaches to identify trends in evidence development and use.

RESULTS

: In the majority single-arm trial product launch scenarios additional real-world, patient-centric and other outcomes data was used to fill gaps in the evidence package supporting these products. Evidence requirements varied by technology (i.e., precision medicine, advanced therapy, immune-targeting agent, small molecule and other biological) and disease type/prevalence (i.e., oncology vs. rare and population size). The study identified aspects of study approaches used for gap-fill, including study design, data source, statistical approaches used and other factors that do provide insights into acceptable evidence packages used to support single-arm launch scenarios.

CONCLUSIONS

: Our research suggests that acceptable or evidence development approaches in single-arm launch scenarios remains variable, driven by the types of evidence questions that need to be addressed and scenarios factors such as degree of unmet need, availability of alternatives, and disease area.