Proposing an NIH High-Leverage Trials (HILT) Program: Large-scale Research for Repurposing and Supplements

This is a guest article from Nicholas Reville, the Executive Director and cofounder of the Center for Addiction Science, Policy, and Research. He authored the Innovation Agenda for Addiction and speaks internationally on addiction and health policy. CASPR advances research on breakthrough therapeutics and develops novel policy interventions to reduce addiction at a population level. For more, see CASPR.org and Nicholas’ Substack, Recursive Adaptation.

Introduction: An Opportunity in Plain Sight

While the US pharmaceutical industry excels at developing novel, patentable compounds, world-class trials of low-exclusivity treatments, such as dietary supplements and off-patent medications, are pursued neither by industry nor the NIH. In addition to missing opportunities to improve health for all Americans, this trial gap costs the public and the federal government hundreds of billions of dollars a year.

Because supplements and off-patent medications do not have economic mechanisms that lead pharmaceutical companies to run Phase III trials, there is an urgent need to develop reliable, large-scale evidence so that patients and providers can access these treatments.

Americans currently spend ~$70 billion annually on supplements, often acting on fragmented or inconclusive data. Simultaneously, hundreds of off-patent medications with known safety profiles sit on the shelf, untested for new indications because manufacturers do not have the legal exclusivity needed to justify the cost of large, conclusive Phase III trials, even in areas of very high unmet need.

In Senate testimony in 2020, Jay Bhattacharya addressed this ‘market failure’ directly:

“For drugs and therapies on patent, a patent holder has a strong interest in running randomized evaluations and navigating the drug through the FDA’s approval process. By contrast, for drugs and therapies with no patent holder, no one has much interest in funding expensive randomized trials or working assiduously to move through the FDA regulatory process for rapid approval (or even slow approval).”

To solve this gap and open up new treatments and dramatic cost savings, we propose the creation of an NIH High-Leverage Trials (HILT) Program for off-patent drug repurposing and supplements. HILT would fund and run definitive large scale trials and, when appropriate, advance regulatory approvals to ensure broad patient access.

Cutting Waste

There are already scattered examples that demonstrate the cost-saving potential of NIH running trials that industry players will not study.

In 2008, the National Eye Institute (NEI) funded the Comparison of AMD Treatments Trials (CATT) to compare Lucentis (macular degeneration treatment costing ~$2,000 per ...