Priority review vouchers for tropical diseases: Impact, distribution, effectiveness, and potential improvements

By Rethink Priorities, Greer Gosnell, JamesHu, Erin Braid, Tom Hird @ 2024-01-02T21:48 (+30)

This is a linkpost to https://rethinkpriorities.org/publications/priority-review-vouchers

Suggested citation: Gosnell, G., Hu, J., Braid, E., & Hird, T. 2023. Priority review vouchers for tropical diseases: Impact, distribution, effectiveness, and potential improvements. Rethink Priorities. https://rethinkpriorities.org/publications/priority-review-vouchers.

Funding statement: We thank Open Philanthropy for commissioning and funding this research report. The views expressed herein are not necessarily endorsed by Open Philanthropy.

Editorial note

The report evaluates the value and effectiveness of the United States' Tropical Disease Priority Review Voucher Program, which was initiated in 2007 to incentivize research and development for medical products targeting neglected tropical diseases. (While PRVs have since been legislated for purposes, we focus our attention on this application.) Specifically, we describe some of the program's history to date (e.g., past issuances, voucher sales/use dynamics, and evidence of gaming), the usage extent of PRV-awarded medical products, academic and anecdotal evidence of the program's incentive effect, and ways in which we think the program could be improved.

We have tried to flag major sources of uncertainty in the report and are open to revising our views as more information becomes available. While preparing this report for publication, we learned that Valneva was awarded a PRV for developing the first Chikungunya vaccine in November 2023 (Dunleavy, 2023), but we did not incorporate this information in the report or associated spreadsheets.

We are grateful for the invaluable input of our interviewees. Please note that our interviewees spoke with us in a personal capacity and not on behalf of their respective organizations.

Executive summary

We catalog information about the 13 issuances of Priority Review Vouchers (PRV) under the United States’ Tropical Disease PRV Program and, for the seven cases with sufficient data, attempt to estimate the number of treatment courses per 1,000 relevant disease cases, or “use rate.” Among the seven products with use rate estimates, we find three with high use rates (>100 courses per 1,000 cases), two have medium use rates (10-100), and two have low use rates (<10). We also find that while all high-use-rate products have been on the market for >10 years, not all products marketed for that long achieve high use rates, and find diverse outcomes in use-rate trajectories, including sharp discontinuities and both upward and downward trends.

Given that PRV recipients can either use or sell their voucher, we also explore the dynamics of how the PRVs’ value is distributed among different types of players in the industry. We find that PRV sales proceeds go toward repayment for shareholders of small pharmaceutical companies or toward (promises of) further drug development for neglected tropical diseases. Large pharmaceutical companies that receive PRV awards tend to retain or use the voucher for faster FDA review of a profitable drug in their pipelines.

Additionally, we review four academic studies that attempt to quantify the effectiveness of PRVs at inducing medical innovations for neglected tropical diseases. Based on their findings and our assessment of study quality, we think it is unlikely that the TD PRV Program had a large, consistent effect on R&D for tropical diseases, but that the results are potentially consistent with a small marginal effect. Additionally, there is historic anecdotal evidence of “gaming the system” — seeking a voucher for a drug that has already been developed and marketed outside of the US — though we think it is unlikely to continue to be an issue going forward given that the opportunities to do so have likely been exhausted.

We then formulate a rough estimate of the value of the TD PRV Program to Open Philanthropy, focusing on a case study of willingness to pay (WTP) for the development of a single drug (pretomanid). While the estimate suggests a value in the tens of millions of US dollars for one drug (implying a WTP in the tens of thousands of dollars), we caution against excessively anchoring on these results given significant uncertainty regarding model structure and inputs.

Finally, several possible improvements to the PRV program emerged from the literature and conversations with experts. These include advocacy to limit the growing supply of PRVs, to require access plans (and proof of follow-through) to earn a PRV, to increase administrative transparency and clarity, and to tie the value of the PRV to the social value of the medical innovation (rather than the voucher). We discuss experts’ critiques of the voucher program as well as opportunities beyond the PRV to incentivize research and development in the field of neglected tropical diseases.

Acknowledgments

This report is a project of Rethink Priorities — a think tank dedicated to informing decisions made by high-impact organizations and funders across various cause areas. The authors are Greer Gosnell, James Hu, and Erin Braid. James Hu edited and reformatted the client-facing version of the report to transform it into a public-facing report. Thanks to Tom Hird for his guidance; Jenny Kudymowa and Melanie Basnak for their helpful feedback; Adam Papineau for copyediting; and Rachel Norman for assistance with publishing the report online. Special thanks to Alex Bowles and Jacob Trefethen (both Open Philanthropy) for their support throughout the project. Thanks also to Matt Clancy (Open Philanthropy), David Ridley (Fuqua School of Business, Duke University), and Murray Lumpkin (Bill & Melinda Gates Foundation) for taking the time to interview and share invaluable insights with us.

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