Aligning Investments in Therapeutic Development with Therapeutic Need: Closing the Gap (2025)
Chapter: Front Matter
Consensus Study Report
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This activity was supported by contracts between the National Academy of Sciences and Gates Ventures and Peterson Center on Healthcare. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2025. Aligning investments in therapeutic development with therapeutic need: Closing the gap. Washington, DC: National Academies Press. https://doi.org/10.17226/29157.
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COMMITTEE ON STRATEGIES TO BETTER ALIGN INVESTMENTS IN INNOVATIONS FOR THERAPEUTIC DEVELOPMENT WITH DISEASE BURDEN AND UNMET NEEDS
DONALD M. BERWICK (Cochair), Institute for Healthcare Improvement
ELLEN MACKENZIE (Cochair), Johns Hopkins University Bloomberg School of Public Health
STACEY J. ADAM, Foundation for the National Institutes of Health
MARIA ELENA BOTTAZZI, Baylor College of Medicine and Texas Children’s Hospital
MACARIUS MWINISUNGEE DONNEYONG, The Ohio State University
STACIE B. DUSETZINA, Vanderbilt University School of Medicine
HOLLY FERNANDEZ LYNCH, University of Pennsylvania
TIMIAN M. GODFREY, University of Arizona College of Nursing (until November 20, 2024)
HOWARD SCOTT HOWELL, Blue Line Advisors, LLC; University of California, Berkeley; The Ohio State University
MARK OLFSON, Columbia University; New York State Psychiatric Institute
LISA LARRIMORE OUELLETTE, Stanford University
EDITH A. PEREZ, Mayo Clinic
KATHRYN A. PHILLIPS, University of California, San Francisco
JOSHUA A. SALOMON, Stanford University
DAVID I. SCHEER, Scheer & Company, Inc.; OrphAI Therapeutics, Inc.; Refactor Health; Adela, Inc.; and BiologicsMD, Inc.
WU ZENG, Georgetown University
Study Staff
ALEX HELMAN, Study Director and Senior Program Officer (as of September 16, 2024)
VERONICA WALLACE, Study Director and Senior Program Officer (until September 16, 2024)
SAMANTHA SCHUMM, Program Officer (from September 30, 2024, to April 25, 2025)
AJA DRAIN, Research Associate (as of November 27, 2023)
ANDREW MARCH, Program Officer (as of April 16, 2025)
ASHLEY BOLOGNA, Research Assistant (as of October 18, 2024)
ELIZA SOUSER, Senior Program Assistant (from October 16, 2023, until August 23, 2024)
RACHEL AMHAUS, Program Assistant (from August 26, 2024, until October 17, 2024)
LAURENE GRAIG, Senior Program Officer (until September 11, 2024)
CLARE STROUD, Senior Board Director
SHARYL NASS, Senior Board Director
National Academy of Medicine Fellows
SANKET DHRUVA, Assistant Professor of Medicine, University of California, San Francisco; San Francisco Veterans Affairs Medical Center
INMACULADA HERNANDEZ, Professor, Division of Clinical Pharmacy University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences (until April 4, 2025)
Consultants
STEPHEN LIM, University of Washington
JENNIFER SAUNDERS, Writer and Rapporteur
Reviewers
This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following individuals for their review of this report:
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report, nor did they see the final draft before its release. The review of this report was overseen by ALFRED BERG, University of Washington, and WALTER FRONTERA, University of Puerto Rico. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
Acknowledgments
To begin, the committee would like to express its gratitude to the sponsors of this study. Funds for the committee’s work were provided by Gates Ventures and the Peterson Center on Healthcare.
Numerous individuals and organizations made important contributions to the study process and this report by providing public testimony, submitting written comments, and more. The committee wishes to express its gratitude for each of these contributions, although space does not permit identifying them all here.
The committee wishes to express special thanks to Stephen Lim, professor and senior director at the Institute for Health Metrics and Evaluation, who served as a consultant to the committee and generously shared data to help the committee with its analysis on investments from industry. The committee would also like to thank the two National Academy of Medicine fellows, Drs. Sanket Dhruva and Inmaculada Hernandez, for their contributions throughout its work.
Lastly, the committee would like to express its gratitude to the National Academies’ staff, who were critical in guiding their work. The committee gives a special thanks to Aja Drain for her research assistance and for being such a positive light throughout this committee process.
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Public Investment in Therapeutic Development
Private-Sector Funding and Priorities for Biopharmaceutical Research
Additional Factors to Consider
Prioritization Methods in the Literature
4 FACTORS CONTRIBUTING TO MISALIGNMENT BETWEEN INVESTMENT PRIORITIES AND UNMET NEED
5 STRATEGIES TO BETTER ALIGN INNOVATIONS WITH DISEASE BURDEN AND UNMET NEED
Targeted Programs to Address Unmet Medical Needs
Aligning Innovation with Value
Goal 2: Support and Strengthen Investments in Innovative Therapeutics that Address Unmet Need
Goal 4: Strengthen a Regulatory Environment that Supports Innovation to Address Unmet Need
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Preface
We can summarize the statement of task for our committee in four questions: (1) Given the current and future burdens of illness in the United States, what are the unmet needs for medications to treat them? (2) What medications are now, or will soon be, under development? (3) How well aligned, or mismatched, are the answers to Questions 1 and 2? (4) To the degree they are mismatched, why? And what changes in policy, payment, investment, and incentives would help close the gap?
Simple to ask, but hard to answer.
Question 1 calls for data on patterns of burden of illness that are accessible from a variety of sources, but “burden of disease” is multidimensional and eludes a consensus definition. Moreover, uncovering how to define “effectiveness” for the myriad of illnesses, and which needs are “unmet” proves to be a difficult task. Furthermore, assessing the degree of unmet needs turns out to require not just statistical and epidemiological analysis, but also value judgments when comparing the multiple dimensions of need across different conditions. For example, how shall rare but serious diseases be compared with more common ones through the lens of need? The committee eschewed a simple numerical comparison, but what, then, is the measuring stick?
Question 2 is even harder than Question 1, in part because the relevant information lies largely in the private sector, is largely proprietary, and is nowhere assembled into large, openly accessible databases that embrace both public and private sources. Moreover, what metric of “development” works well? The dollars in research budgets? The number of drugs trials? Patents issued?
Answering Question 3 (How big is the mismatch?) would require access to and aggregation of largely proprietary information on private-sector drug development, as well as difficult-to-estimate probabilities of success for medications now in the research pipeline. The Food and Drug Administration (FDA), foundations, and the private sector have a great deal of information on proposals for drug development and approval, but much of it was not accessible to us owing to its proprietary nature.
And Question 4, about achieving better alignment between unmet need and investment, surfaces how little we actually know about which policies and payments truly have leverage and which do not. Despite 4 decades of policy initiatives with the intent to encourage specific investments, including, for example, the 1983 Orphan Drug Act, priority review voucher programs, modifications in patent protections, and changes in FDA review and approval criteria, the landscape has much more opinion than hard evidence about their effect on decision making for investment, and the two—opinion and evidence—often conflict.
In spite of the challenges described above, our committee stepped cautiously and thoughtfully into this difficult terrain. As cochairs, we were fortunate to have a group of unusually expansive breadth in experience, subject-matter knowledge, and research experience. Among the members were clinicians; senior researchers; experts in law and ethics, drug development, market access, and investments; seasoned public servants; epidemiologists; and statisticians. Importantly, the committee also included members who had real or perceived conflicts of interests, but whose expertise was judged essential to our deliberations and who participated only with full transparency as to their roles and interests.1 They proved invaluable to the process.
Our Consensus Report reflects more than a year of careful deliberations. Some uncertainties were resolved as we went along, such as our emerging, shared realization that no single metric of “burden” or “unmet need” would be feasible, as value judgments overlapped inevitably with evidence and data. We also developed a much better and more nuanced view of the historical role of FDA, and a view that, on the whole, to the degree that investments are not matching unmet needs, FDA, far from being a root cause of the gap, has been, to the extent law allows, a constructive and valuable force for improvement. Similarly, the National Institutes of Health (NIH) and its centers play a vital role in the pipeline of drug discovery. Indeed the investment of the United States in innovative research that saves lives and improves the public’s health has, for many years, been revered around the world.
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1 See Appendix C for Disclosures of Unavoidable Conflicts of Interest.
However, at the time of release, the innovation ecosystem, federal funding, and institutional architecture are undergoing unprecedented and rapid change, seriously threatening our ability to sustain this position. Terminating grants midstream, as is currently being done, and limiting opportunities for new research that is judged important and scientifically sound by an independent community of peer scientists will likely impede innovation. The committee strongly recommends bipartisan congressional and executive branch support of NIH, FDA, and other federal agencies that are vital to the continued success of the biomedical research enterprise in the United States.
Other uncertainties proved more challenging, such as how to judge the widespread lack of evidence to support the effectiveness of currently available policy initiatives that purportedly aim to address unmet need whose supporters have strongly held views and important anecdotal testimony. More than once, we heard “absence of evidence is not evidence of absence” from those who believe strongly in the value of some of these initiatives, such as priority review vouchers or Orphan Drug Act subsidies. Our recommendations, we believe, reflect a prudent middle road.
As if the Statement of Task were not broad and challenging enough, our committee’s mandate did not extend to addressing the root causes of a substantial portion of unmet need in America. Although access to existing therapeutic innovations, itself, was not a major focus of our Statement of Task, it would be naïve and harmful in the extreme in a report on unmet needs not to flag persistent inequities affecting access to treatment, as elevated in the fundamental National Academies report Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care, as a major reason for remediable disparities in health care and health in America.
The science is unequivocal and the implications unavoidable that racial, socioeconomic, and other forms of inequality in the United States affect and, in many cases, cause underinvestment in needed treatments and cures and, even more powerfully, create barriers to access and adherence to effective treatments, once developed.2,3
Any commitment to closing the gaps between unmet needs and therapy development must include a commitment to improving the policies and practices intended to eliminate or at least reduce existing disparities in access and use. Even the most efficacious drug therapy will miss meeting important proportions of unmet needs if not available and accessible to those most in need.
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2 National Academies of Sciences, Engineering, and Medicine. 2024. Ending Unequal Treatment: Strategies to Achieve Equitable Health Care and Optimal Health for All. Washington, DC: The National Academies Press. https://doi.org/10.17226/27820.
3 Institute of Medicine. 2003. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. Washington, DC: The National Academies Press. https://doi.org/10.17226/12875.
We would like to express our deepest thanks to our committee members and the National Academy of Medicine Fellows who joined our deliberations. We have rarely experienced a group process endowed with such gracious listening and authentic dialogue among members who did not always agree at the start and whose convictions ran deep. That we arrived at a Consensus Report with which all now concur and that was not watered down testifies to this group’s maturity and skills. Equally, we are all deeply in debt to the marvelous National Academies staff who supported our work and, in many ways, led us. There would have been no report without them.
Donald Berwick and Ellen MacKenzie, Cochairs
Committee on Strategies to Better Align Investments in Innovations for Therapeutic Development with Disease Burden and Unmet Needs
May 2025
