Pulmonary arterial hypertension (PAH) is a condition characterized by high blood pressure in the pulmonary artery that carries blood from the heart to the lungs. Clinical trials have led to a growing number of treatment options that can improve symptoms and clinical outcomes for patients with PAH. In a recent international task force summary paper published in the European Respiratory Journal, led by CVC faculty member Dr. Jason Weatherald, researchers examine the trajectory of PAH clinical trial end-points and assess how emerging technologies and innovative trial designs can potentially facilitate new PAH drug development.
PAH drugs have historically targeted one of three pathobiological pathways and function predominantly through pulmonary arterial vasodilation, a widening of the artery to increase blood flow. In Phase 3 clinical trials for PAH the primary end-points must take into account how patients feel, function, or survive, however, this prevailing model has also been challenged more recently as a result of emerging therapies and cutting-edge trial design.
In order to adequately implement novel therapies, the researchers indicate that PAH trials need to optimize trial design and efficiency, and develop end-points that are both innovative and meaningful. Based on the findings of this review, they provide four comprehensive recommendations:
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Ensure all components of combined primary and secondary end-points are clinically meaningful, and that patients are engaged in both the trial design and end-point selection process.
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In the instance that traditional end-points are replaced by biomarkers, which have the potential capacity to reduce both the scale and duration of clinical trials, biomarkers must be rigorously developed and validated in order to ensure they are a suitable replacement.
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There is an opportunity to improve clinical trial operations and efficiency through emerging artificial intelligence technologies, provided that statistical and methodological systems continue to be implemented carefully.
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Clinical trials must improve access, participation, and diversity globally, especially given the variability of the causes of PAH and its patient and disease characteristics.
