Using Real-World Data to Optimize Strategic Planning for Pulmonary Arterial Hypertension Clinical Trials

Abstract

Introduction Pulmonary arterial hypertension (PAH) clinical trials are evolving from small, surrogate endpoint studies based primarily in North America (NA) and Western Europe (WE), to larger, clinical endpoint trials with investigative sites around the world. Limited clinical trial experience with PAH beyond NA and WE presents a challenge to planning key elements of a study such as determining country and site selection and predicting event rates. We sought to develop a data-driven approach to estimate event rates and optimize strategic planning for PAH clinical trials. Methods We used the IMS prescription database, which includes prescription data from hospital, retail, mail service, and long-term care pharmacies in over 90 countries. We reviewed global prescription data to characterize the use of cornerstone PAH therapies in various countries as days of treatment per population count. We used this information to determine which countries had a higher use of PAH drugs and where combination therapy vs. monotherapy was most likely to be used. We reviewed previous PAH clinical trials to estimate time to clinical worsening (TTCW) rates for patients receiving monotherapy (∼25-30% events/yr.) vs. combination therapy (∼15-20% events/yr.). Results Regions and countries with the highest consumption of PAH specific drugs were NA, WE, and Japan ( Figure ). The lowest use of PAH specific drugs was in Latin America (LA). Endothelin receptor antagonists (ERAs) were used in countries throughout NA, WE, Eastern Europe (EE), and Asia. Use of newer therapies occurred only in select regions: riociguat, a soluble guanylate cyclase stimulator, was used mostly in WE, EE, Canada, Japan, and Taiwan, and selexipag, a prostacyclin receptor agonist, was used mostly in NA, WE, and Japan. Conclusions Our analysis showed that greater use of PAH specific drugs occurred in higher income regions such as NA, WE, and Japan; therefore, we predicted greater use of combination PAH therapy in these areas. There was lower use of PAH specific drugs in EE, LA, and Asia; thus, we predicted a higher prevalence of monotherapy in these regions. Understanding global prescription patterns and associated estimated event rates may allow for a more data-driven approach to developing enrollment timelines and selecting countries and sites for PAH clinical trials.