Translational Science in Drug Development: Surrogate Endpoints, Biomarkers, and More

As the biological mechanisms of diseases and pharmacological activities of therapeutics are better understood, this information provides opportunities to improve clinical trial efficiency. One such opportunity includes identification and use of surrogate endpoints that indicate disease progression or clinical response in clinical trials. In instances where disease progression or clinical response is slow, surrogate endpoints may provide a measurable prediction of the outcomes for clinical trials in a shorter and more feasible timeframe [1]. Development and validation of such surrogate endpoints, however, often requires sustained efforts and dedication from many stakeholders.

Surrogate endpoints represent only one way that translational science can be leveraged to support clinical development of medical products. Understanding the causal pathways of a disease can support the identification of prognostic or predictive biomarkers. Animal models of disease can provide supportive evidence for candidate therapeutics when the pathophysiology of disease is well understood and the animal model recapitulates important aspects of the human disease. When developing these types of mechanistic evidence to support a clinical development program, early discussions with regulators on the type(s) of evidence and how the evidence would be used can be beneficial.

Collaboration between academic researchers, industry, clinicians, patient organizations, and regulators can drive innovation and facilitate the use of translational science during clinical development [2]. This workshop will focus on best practices and provide use cases for successfully bringing forward evidence generated through translational science for regulatory submissions. Stakeholders will discuss potential barriers to using translational science to support therapeutic development and strategies to overcome those barriers.

Workshop Objectives

• Present efforts from FDA, NIH, academia, patient groups, and industry to support surrogate endpoint and other biomarker identification and development for use in therapeutic development and regulatory submissions
• Provide successful examples of using translational science in the development of therapeutics.
• Identify current challenges and opportunities in developing innovative drug development tools and applying them in therapeutic development.
• Foster interaction and discussion among the stakeholders who are developing these tools and implementing them in therapeutic development programs

References

[1] Mack, A., et al., Perspectives on biomarker and surrogate endpoint evaluation : discussion forum summary. 2011, Washington, D.C: The National Academies Press.

[2] Luke, D.A., et al., The Translational Science Benefits Model: A New Framework for Assessing the Health and Societal Benefits of Clinical and Translational Sciences. Clin Transl Sci, 2018. 11(1): p. 77-84.

Funding Acknowledgement

This workshop is supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award (U19FD006602) totaling $3,344,533 with 100 percent funded by FDA/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.