Summary¹

The United States has long been a leader in biomedical research, generating new therapeutic breakthroughs and innovations that advance the health of our nation and the world. Research in both the public and private sectors contributes to the greater understanding of human health and disease and to the development of new technologies that lead to exciting clinical benefits for patients.

However, conducting this important research requires making complex decisions about where to focus resources and investment. In principle, investment in therapeutic development should follow the diseases and conditions with the highest unmet need and burden of disease. But both public and private funders developing therapeutics consider disease burden and unmet need in the context of myriad other competing considerations and goals in determining where to invest, such as limited funding; balancing advancements in basic, translational, and clinical science; advocacy from patient groups; the likelihood of regulatory approval and associated challenges; payer reimbursement; market competition; and overall timing and overall profits and return on investment. These competing practical and financial priorities do not always align with diseases with the highest burden and unmet needs. In addition, how to fairly allocate resources for drug development among potential beneficiaries involves ethical considerations and value judgments about which there is not universal agreement and for which there are a multitude of defensible approaches.

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¹ References are not included in this report summary. Citations appear in subsequent report chapters. Key terms used in this summary and throughout the report are defined in Box 1-2.

These competing goals and judgments can hinder the research system’s ability to prioritize disease burden and unmet need. For example, despite considerable investment in therapeutic development in the United States, substantial disease burden and unmet need remain in areas such as treatment for mental illness, cancer, cardiovascular disease, Alzheimer’s disease, and immunological disorders to name a few, as well as broadly across the realm of rare and neglected tropical diseases. Some diseases and conditions have no available therapies, and often the existing, approved therapies are only modestly effective, have unclear clinical benefits, or have significant safety risks. Thus, the current system of drug development needs adjusting to improve the alignment of public and private investment in therapeutics with areas of unmet needs.

COMMITTEE TASK AND APPROACH

With support from Gates Ventures and the Peterson Center on Healthcare, the National Academies of Sciences, Engineering, and Medicine formed the Committee on Strategies to Better Align Investments in Innovations for Therapeutic Development with Disease Burden and Unmet Needs. The committee consisted of 16 members with a broad range of expertise, including health economics, data science, epidemiology, health policy, biomedical and pharmaceutical sciences, therapeutic development (including those with experience in the biopharmaceutical industry and the investment community), regulatory oversight, health law, bioethics, social, and behavioral sciences, clinical care, and health disparities. The committee was tasked with describing current U.S. disease burden, characterizing the degree and patterns of mismatch between that burden and public and private innovation in therapeutic development, describing challenges in better aligning innovations in therapeutic development with disease burden and unmet need, and proposing strategies and recommendations to improve alignment.

The committee approached its statement of task with the objective of designing policies such that society invests in innovation (including public and private investments) up to the point where the marginal cost equals the expected marginal social benefit of those investments. While cost is relatively straightforward to calculate (i.e., as the sum of private and public investment), the expected social benefit of these investments is complicated to determine. Benefit depends on the estimated reduction in disease burden for a given investment as well as on ethical judgments about how to value different kinds of health gains and inequality reductions, depending, for example, on such factors as the size of the population affected, disease severity in the context of duration or quality of life, the age of typically affected patients, and prevalence among otherwise marginalized groups. Therefore, rather than prescribing a single approach to calculating disease

burden and unmet need or providing a definitive list of disease or therapeutic areas where investments should be directed, the committee sought to provide guidance that could accommodate different values and priorities while still facilitating alignment among innovation, disease burden, and unmet need. To demonstrate the barriers and solutions to misalignment, the committee developed a conceptual framework that outlines key themes of this report (Figure S-1).

The committee’s recommendations are organized around five goals, which are discussed in the following sections:

1. Design a state-of-the-art publicly accessible system to assess and track unmet need associated with U.S. disease burden, with a critical focus on identifying areas of mismatch and reducing health disparities.
2. Support and strengthen public investments in innovative therapeutics that address unmet need.
3. Strengthen public–private partnerships to encourage the sharing of information and technology transfer to facilitate addressing unmet need.
4. Strengthen a regulatory environment that supports innovation to address unmet need.
5. Strengthen a fiscal and policy environment to align reimbursement policy with evidence-based therapeutic value and the extent to which products address unmet need.

EVALUATING DISEASE BURDEN AND UNMET NEED

Although there is not a single metric universally accepted to measure disease burden, unmet need, or innovation, the committee examined the literature and spoke with outside experts to better understand the extent to which there is a mismatch in investments for innovation with disease burden and unmet need. The committee found that the current data on U.S. disease burden, unmet need, and investment in therapeutic development have significant gaps and limitations. Although there are some existing data, they are not regularly compiled and synthesized for assessing mismatch across factors. As a result of these limitations in the data, this committee lacked the data needed to produce a comprehensive evaluation of all aspects of disease burden, unmet need, and investment to fully assess the mismatch. However, the committee did find that some therapeutic areas are underinvested in relative to disease burden, such as chronic conditions like cardiovascular disease and chronic obstructive pulmonary disease. The committee’s analysis of National Institutes of Health (NIH) funding versus disease burden also highlighted the lower public investment in such

conditions as headaches, neck and back pain, psoriasis, and gallbladder diseases.² The literature sources on private-sector investment, though limited, indicate substantial investment in oncology and neurological disease and suggest underinvestment in cardiovascular disease, immune-related disorders, and maternal and neonatal conditions.

Given the reality that resources are limited and cannot be simultaneously directed toward all health and research needs, a systematic approach is needed to set research priorities and funding allocations to address public health needs. Currently, leaders have imperfect data upon which to make scientifically informed policy judgments. Limitations in the availability of data necessary to assess how investments in therapeutic development align with disease burden and unmet medical need is one factor that contributes to misalignment between investments in therapeutic development and unmet medical need during research prioritization. As a result, public research funds are being allocated each year with insufficient information about the extent to which the investment addresses public health needs.

Conclusion 3-1:³ More comprehensive, specific, timely, and accurate data on disease burden, unmet need, and innovation, as well as improved data aggregation, are essential for private and public funders to systematically use measures of disease burden and unmet need when making decisions about funding priorities.

A publicly accessible, centralized system to aggregate relevant data and track unmet medical needs associated with disease burden would enable more strategic investment of resources and would help policy makers and public and private funding groups better align innovation and investment with public health needs. This system could be used to identify disease areas in which to prioritize investment and to highlight areas of mismatch between investment and disease burden—including both underinvestment in some conditions and overinvestment relative to burden in others. Having access to data on burden, need, and current measures of public and private investment would enable public and private funders to make informed decisions based on their priorities and values. For example, some may prioritize rare, low-prevalence diseases with high individual burden, while others may prioritize diseases with high population burden or high health disparities.

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³ The conclusions in this summary are numbered based on how they present in the chapters of the report.

² See analysis in Chapter 3, “Degree and Patterns of Mismatch Between U.S. Disease Burden and Public and Private Investment in Innovative Therapeutic Development.” Terms for diseases and conditions are drawn from the Institute for Health Metrics and Evaluation Global Burden of Disease dataset.

Developing such a system is challenging. For instance, both burden and unmet need can be interpreted in multiple ways and must be carefully defined in designing this system. Current investments are similarly difficult to assess, especially in the private sector. In addition, while some data are readily available and could be aggregated for this purpose, the committee recognizes that not all the data described in Recommendation 1 are currently or easily accessible. Nevertheless, collecting these data is essential to advancing public health and reducing health disparities. Finally, it is critical that the information collected on evaluating disease burden, unmet need, and the areas of investment be made public for all to use.

Conclusion 3-2: Collecting and aggregating these data requires ongoing stewardship to most effectively address unmet clinical need and reduce health disparities.

Conclusion 3-3: The U.S. government has a responsibility to ensure that timely data on public investment and population health data be made publicly available to support research and strategic investment in areas of unmet need.

Following these conclusions, the committee specifically recommends the following:

Recommendation 1: Congress should establish and fund an interagency consortium charged with tracking and assessing unmet therapeutic need associated with U.S. disease burden and current investments in innovation, with a critical focus on identifying areas of mismatch and reducing health disparities. The consortium should be led by a relevant unit of the Department of Health and Human Services (HHS) as determined by the secretary of HHS.

This consortium should be charged with the following:

1. Generate a publicly accessible data repository on disease burden, therapeutic investment, and unmet needs that is updated on a triennial basis and used to generate derivative reports.
2. Produce a triennial report to Congress on the status of U.S. disease burden, extent of unmet need, and areas in which additional data are needed to reliably assess burden and unmet need. This report should collate, at minimum, for each disease area the current and projected incidence, prevalence, mortality, and disability-adjusted life-years.
3. Produce a companion assessment of the most reliable current estimates of investments from the public and private sectors for each therapeutic area, including public-sector funding by type

3. and amount; private-sector investments; stage of the development pipeline for emerging treatments (e.g., drug discovery, preclinical research, clinical trials, regulatory review and approval, postapproval surveillance); the number, phase, and status of clinical trials; and sources of funding.
4. Identify areas in which additional research is needed to provide any missing information for each item above and recommend ways, such as statutory requirements or surveys, by which the data could be gathered for subsequent reports.

To implement this recommendation most effectively, this consortium should involve cross-agency and disciplinary collaborators, including the Food and Drug Administration (FDA), NIH, Advanced Research Projects Agency for Health (ARPA-H), Centers for Disease Control and Prevention (CDC), the Office of the Assistant Secretary for Planning and Evaluation, as well as many other federal agencies and key partners, such as the Patient-Centered Outcomes Research Institute and industry organizations. It is important for this consortium not only to collate these data but also analyze and synthesize the data, including identifying gaps and ways to fill them. For example, given the challenge of collecting information on private industry investments, companies may need incentives to share or disclose some of these data that are not now publicly available. One way of collecting this information could be through a survey of pharmaceutical and biotech companies, which, while imperfect, could gather a useful sampling of data to gain insight into private investment in therapeutic development. The collecting of these data could be incentivized by allowing early access to updated datasets and reports to private and public companies that have contributed to the repository, which would provide a valuable, precompetitive output that companies could use to inform business decisions.

REASONS THERE IS A MISMATCH BETWEEN INVESTMENT, DISEASE BURDEN, AND UNMET NEED AND RECOMMENDATIONS TO ADDRESS THEM

Accelerating medical breakthroughs and enabling individualized screening, prevention, treatment, and care for all depends on the entire innovation pipeline from basic science through clinical trials, regulatory approvals, and postmarketing evidence generation and implementation. A barrier in any one of these areas can slow or halt innovation. Although there are many challenges and barriers in drug development broadly, the committee focused on the reasons for underlying mismatches between research and development (R&D) investments and areas of unmet need. The committee

identified two high-level factors that underlie the observed mismatch: scientific challenges and market forces.

Scientific Challenges

A lack of understanding of underlying pathophysiology is a fundamental barrier to therapeutic development for many diseases, such as Alzheimer’s disease and mental health conditions. Life science investors and industry scientists depend on advances in basic and preclinical biomedical research, areas that have traditionally been funded largely by NIH, to direct their attention and funding. The committee also identified scientific challenges in measuring outcomes for some conditions, such as chronic pain, when measures are subjective, highly variable, or difficult to characterize. Similarly, a lack of plausible surrogate endpoints in some disease areas prevents drug developers from using the accelerated approval pathway, which is designed to bring therapeutics to market faster on the condition that they complete postmarketing studies to confirm clinical benefits. The committee found that investment in preclinical biomedical research is essential to driving innovation in disease areas with significant burden and unmet needs.

These investments in research must be informed by the comprehensive system to track and assess disease burden and unmet needs, as outlined in Recommendation 1. Congress plays a key role in defining the parameters of public investment in medical research by setting appropriations among the NIH’s institutes and centers. Information about burden and unmet need should be incorporated at key points of decision making and should serve as a key input for determining congressional appropriations and funding decisions at NIH and other federal agencies.

However, considering the burden and unmet need should not be limited to appropriations. Such considerations should be explicitly integrated throughout the research funding process, from program development to grant review criteria, ensuring that unmet need is considered alongside scientific merit in grant mechanisms. This holistic approach would help align incentives by encouraging investigators to consider unmet needs early in the research process. When funding agencies elevate the goal of addressing unmet need as a priority, researchers are more likely to develop studies to target these areas, leading to better alignment of public and private investment in medical research with public health needs.

Recommendation 2: Funders of biomedical research should consider disease burden and unmet need when setting research priorities and directing funding. Specific actions to ensure both population health needs and scientific merit are considered in grant funding mechanisms include:

1. Congress should consider disease burden and unmet needs when setting appropriations to agencies that fund biomedical research, including in allocating funding among National Institutes of Health institutes and centers.
2. Public and private funders should develop targeted research funding opportunities specific to diseases with the highest mismatch of burden and unmet need, including funding opportunities for innovative methods to enable the development of therapeutic products and new biomarkers for diagnostic test development in these areas.
3. Public and private funders should allocate funds for the development and validation of new biomarkers and surrogate endpoints for diseases with high unmet medical need.
4. Public and private funders should provide funding for studies of disease epidemiology or basic science for areas where there is a critical need for understanding the mechanisms of disease.
5. Public and private funders should include explicit criteria that include, but are not limited to, unmet need and disease burden for evaluating proposals in the grant review process and funding decisions.

In addition to directing investments in biomedical science toward unmet needs, it is important to ensure a robust infrastructure exists for regulatory review to facilitate drug approval and surveillance in these areas. Although FDA sometimes is cited as a barrier to innovation, the committee did not find evidence to support the claim that misalignment between investment and unmet need was attributable to action or inaction from FDA. In fact, FDA has several ongoing programs to drive innovation in much-needed areas. These programs generally fall into three categories: (1) efforts to encourage investment to address unmet need; (2) efforts to address broad scientific challenges, improve coordination, and encourage data generation to address unmet need; and (3) efforts to facilitate and expedite development and review to address unmet need. After extensively reviewing the evidence around these programs, the committee made the following conclusion:

Conclusion 5-3: Additional resources are needed for FDA programs that successfully support endpoint development and validation, innovative trial design, and the resolution of other broad scientific challenges that impede drug development for unmet needs, as well as programs designed to support communication between sponsors and FDA to quickly resolve challenges arising in specific development programs.

Recommendation 6: To maintain the appropriateness of Food and Drug Administration (FDA) programs that expedite the development and review of therapies in areas of unmet need, including the accelerated approval program, FDA should generously use its authority to impose postmarket study requirements, ensure that required postmarket studies are appropriately designed to confirm clinical benefit, and strictly enforce postmarket study requirements. The following steps will support these goals:

1. FDA should ensure that confirmatory studies are well designed to evaluate clinical benefit, and should prespecify the study results that will be deemed acceptable for conversion to traditional approval.
2. FDA should continue recent efforts to ensure that confirmatory studies are underway before approval is granted, making exceptions only in extreme cases.
3. If concerns about timely study completion arise during progress reports, then FDA and the sponsor should determine the steps needed to address barriers; any modification to study requirements should prioritize ensuring rigor.
4. For drugs whose studies fail to confirm clinical benefits following flexible approval, FDA should use its authority to rapidly withdraw approval.
5. FDA should lead an effort, in collaboration with the National Institutes of Health and the Centers for Medicare & Medicaid Services, to enable more efficient conversion of unvalidated endpoints to validated endpoints to advance therapeutic innovation.

FDA currently exercises a great deal of regulatory flexibility, including beyond that offered in existing programs, such as through the use of accelerated approval. Regulatory flexibility can be appropriate as long as there is an expectation that clinical benefit will be confirmed within a reasonable time frame after approval and that those expectations are enforced by requiring rigorous confirmatory studies to be completed in a timely manner and rapidly acting on their results.

While greater regulatory flexibility can speed access to promising therapeutics, what patients truly need are safe and effective therapeutics. Thus, flexibility must be balanced against the importance of maintaining strong regulatory standards. For example, regulatory flexibility may be unavoidable for certain rare diseases, where it is nearly impossible to meet standard expectations. However, regulatory flexibility that allows for approval when trials fail to show clinical benefit raise a number of concerns, including the possibility of misleading patients, inhibiting the development of the information necessary to guide clinical decision making, and impeding the conduct of clinical trials for other drugs that may be more efficacious, both by

discouraging further trial participation and influencing expectations around standard-of-care comparators.

Occasionally, FDA has extended its flexibility by wide margins to approve drugs despite substantial uncertainty about their benefit, including drugs that failed to meet prespecified endpoints in pivotal or confirmatory studies. Despite this expansive current flexibility, FDA faces frequent pressure to go even further. Because weak approval standards harm all patients, and FDA is a public health agency that must consider what is in the best interests of populations, the committee does not recommend approaches that would extend the agency’s flexibility in drug approvals beyond what is currently permitted.

Recommendation 7: To ensure that regulatory flexibility is exercised in a manner that promotes the approval of drugs that are both safe and effective, the Food and Drug Administration (FDA) should uphold strong regulatory approval standards. When FDA exercises flexibility, whether through accelerated approval or outside that pathway, the agency should require rigorous, timely confirmatory studies.

For FDA to maintain many of the existing pathways and initiatives that address areas of therapeutic need, the agency requires appropriate funding and staffing, and agency personnel need appropriate job security. FDA is a staff-intensive agency, with approximately 80 percent of its budget devoted to personnel costs needed to appropriately recruit and retain individuals with the expertise needed to regulate the nation’s food, drugs, and medical devices. Expanding the FDA workforce would allow the agency to keep pace with technological and scientific breakthroughs. However, FDA has faced a number of concerning staff disruptions recently—including layoffs, retirements, and departures—threatening the agency’s ability to manage its intensive workload and advance innovative approaches.

Conclusion 5-8: Support for innovation in the pre- and postmarket settings requires a well-resourced regulatory environment, including attracting and retaining FDA staff with the necessary experience and expertise for innovative technologies.

Recommendation 8: Congress should authorize a significant expansion of Food and Drug Administration (FDA) staffing and consistent resources to support the implementation of Recommendations 6 and 7, and especially to ensure that FDA has sufficient resources to monitor and enforce requirements for postmarketing surveillance and drug evaluation research.

Market Forces

Many factors contribute to investment decisions, but given the involvement of for-profit firms in the financing of drug development, expectations about returns on investment are of major importance. For some disease areas, market forces discourage drug developers from investing in or pursuing therapeutics because the potential earnings or return on investment from a new therapy are too low to justify a further investment in R&D. Rare diseases, by definition, are those that affect small populations; in the United States the cutoff point is typically 200,000 people. The market for these therapies is small, and so for many years the return on investment has been generally considered to be too small for market development. Most rare diseases fall into the categories of ultrarare and hyperrare diseases, making the market for these drugs extremely small.

A second factor that affects calculations for therapeutic investment is the duration of treatment. For drug developers, chronic disease states—where the duration of therapy is unlimited—offer greater opportunities to profit than do acute conditions, on average. This can create a financial disincentive for investors considering returns for curative therapies that have short treatment times.

One potential strategy to address market forces and promote therapeutic development is to use public–private partnerships (PPPs), which can be particularly beneficial for innovation in areas where cost and risk sharing are valuable, such as novel drug target discovery, biomarker testing, or preclinical development models. The committee identified three key areas of unmet needs where PPPs could address innovation challenges:

1. Expand the development of better diagnostics, which is an area that is sometimes difficult for investment from the private sector because of market failures and payment structures for diagnostic tests.
2. Limit situations where therapies that are effective and that meet an unmet need are taken off the market or where assets demonstrating early signs of efficacy are shelved before making it to market.
3. Provide an avenue for the development of drugs for diseases where there exists no economic incentive for the private sector to develop therapeutics.

Conclusion 5-9: Strengthening and expanding public–private partnerships, such as the Network for Excellence in Neuroscience Clinical Trials, the National Cancer Institute Experimental Therapeutics program, and Bridging Interventional Development Gaps, could help address innovation challenges for therapeutic areas with unmet needs.

In addition to recommending additional support for existing PPP models that have shown promise in addressing gaps in the drug development pipelines, the committee makes the following recommendation:

Recommendation 3: U.S. federal scientific agencies with congressionally authorized nonprofit organizations, such as the Foundation for the National Institutes of Health, Centers for Disease Control and Prevention Foundation, Reagan-Udall Foundation, and Henry M. Jackson Foundation for the Advancement of Military Medicine, should increase use of their nonprofits in order to focus on building public–private partnerships in areas of mismatch between unmet need (encompassing both therapeutics and diagnostics) and innovation.

Despite the successes of existing PPPs and the potential to expand these to enhance innovation in needed therapeutic areas, several barriers exist within the United States to developing more PPPs. First, PPPs are often initiated by federal agencies seeking to expand therapeutic development in a specific area. Such agencies approach private firms about entering a PPP to contribute financial support or in-kind resources and assets. In the areas of high unmet need with low economic incentives for the private sector, these PPPs are often focused on shelved assets that companies have developed but chosen not to pursue. However, the federal agencies do not always have insight into what shelved assets exist and therefore are unable to approach companies about developing these assets. Therefore, having an independent organization house a searchable repository of assets to which companies voluntarily submit information could help overcome this barrier. To safeguard proprietary information, such a repository might not be publicly available, but it could be viewed by federal agencies and other foundations and nonprofits that apply for access. Although it likely would not provide a complete list of shelved assets, it would be a start for advancing PPPs in areas of unmet need and where the market does not support further innovation with a specific compound.

Recommendation 4: The National Institutes of Health should work with a neutral third-party entity to set up a searchable repository of assets no longer under development by commercial sponsors to be shared with foundations and other entities to take forward for testing. The information in the repository could be voluntarily provided by companies potentially looking to enter public–private partnerships to develop an asset.

Finally, there is an urgent need to better align payer coverage and reimbursement policies to ensure market access for products addressing

unmet need. Specifically, aligning reimbursement policy with evidence-based therapeutic value could create stronger incentives for investment in products targeting unmet need and also provide patients with improved access to these products. Research indicates that pharmaceutical companies respond to financial incentives and direct innovation efforts toward areas with the greatest financial incentives, so by aligning reimbursement policy with therapeutic value (i.e., how much clinical benefit a drug offers), investment would shift toward developing products with demonstrated clinical benefit addressing unmet needs.

Reimbursement policy through public (e.g., Medicare and Medicaid) and private plans (employer sponsored and individual market health plans) determines both whether a novel drug is covered and, if covered, the amount paid by beneficiaries. Disincentives for innovation can occur if novel drugs that address unmet needs are not covered or are covered but not readily accessible by patients because of access restrictions or cost-sharing that is unaffordable for patients. In addition, providing high coverage and payment for therapies without demonstrated clinical benefit or substantive innovation reduces the potential of reimbursement policy to incentivize the development of high-value treatments. Aligning reimbursement policy with evidence-based value and unmet need is key to this committee’s aims of promoting innovation and addressing unmet need.

A revised approach to reimbursement policy could help address innovation incentives for therapeutical development by linking pricing to evidence-based value assessments that incorporate clinical effectiveness and patient perspectives. Many other countries, including the UK and Germany, offer useful models for this approach of prioritizing payment for new therapies that address unmet need and limiting reimbursement for products that offer marginal improvements or whose clinical benefit remains unproven, although the details of these programs would need to be adapted for the United States. Linking pricing to value is also important because prioritizing payment for high-value innovative therapies (while limiting overpaying for lower value treatments) could make more resources available for improving coverage for effective therapies.

Conclusion 5-10: If public and private payer reimbursement policies were more aligned with evidence of product value and the extent to which a drug addresses unmet medical need, greater innovation would occur in therapeutic areas with high unmet need.

Conclusion 5-11: Congressional action is needed to more directly tie prices and public insurance reimbursement for novel drugs that address unmet need to evidence-supported measures of value or impact.

Recommendation 9: Congress should reform the statutory framework that regulates public reimbursement for novel drugs to better align reimbursement rates with evidence of clinical benefit as compared with existing therapeutic alternatives, if any. This could include:

1. Expand the Centers for Medicare & Medicaid Services’ authority and capacity to negotiate prices beyond the scope of the Inflation Reduction Act to account for the value of the drug relative to alternatives or a standard of care, including the extent to which it addresses unmet need.
2. For drugs with negotiated prices, set reimbursement terms that maximize patient access through more favorable cost-sharing, robust formulary coverage, and more tailored application of utilization management tools (e.g., prior authorization, step-therapy, and quantity limits).

In addition to the broader market challenges for therapeutics, there are specific challenges that must be addressed for one-time, curative, or regenerative medicine therapies. Novel one-time or limited duration curative therapies have been developed in recent years, but it has often proved difficult for them to reach patients. Recent examples have included treatments for hepatitis C, lymphomas and leukemias, beta thalassemia, and sickle cell anemia. With new developments in cell and gene therapies in recent years, the number of such therapies is increasing. It is important that these therapies continue to be developed—some are highly effective and innovative, but the market and access barriers are significant.

The benefit designs and utilization management employed by many insurance payers in the United States make it difficult for clinicians, individual patients, manufacturers, and innovators to navigate coverage and patient access for very high-priced drugs. This has resulted in lower or no access to certain drugs, depending on insurance coverage and even geography (e.g., variation by states among Medicaid insured populations).

Recent evidence also suggests that as commercial products have underperformed, new investments in cell and gene therapies and curative therapies are being challenged, and drug developers have begun to retreat from this market, despite the exceptional benefits of these products for patients (especially those with very rare diseases). To improve affordability and access for patients and to sustain investments in these needed innovative treatments, novel solutions for payment, coverage, and market access for drug developers, payers, and patients are needed.

Conclusion 4-1: Innovative therapies are emerging for rare diseases and other complex conditions, offering a potential for cure. However, the fragmented payment system within the United States is a barrier

to patient access, resulting in underinvestment in developing curative therapies. The current U.S. market and policy environment is unprepared to manage these one-time, very high-cost therapies. There is a need for a clearer reimbursement structure for innovators developing these high-cost curative treatments.

Recommendation 11: Congress should support the development of a negotiation and access model for one-time curative therapies to ensure access for patients and market access for innovators of novel therapies.

To begin this work, Congress could instruct an organization or agency, such as the Medicare Payment Advisory Commission or the Medicaid and CHIP Payment and Access Commission, to study and develop recommendations for legislation to create a new program addressing the unique deficiencies of the nation’s current insurance system in enabling access to curative therapies.

CONCLUSION

Therapeutic innovation in the United States has powered medical innovation around the world, but unmet needs remain. Current research prioritization is done without the data on disease burden, unmet need, and investment needed to guide decision making. A robust, timely, accessible data system is key to implementing recommended changes in policies and practice that can deliver better health outcomes from the resources invested in innovation. With better information on disease burden and unmet need, we can make more strategic investments in basic science. These strategic investments will drive scientific discoveries that enable more efficient clinical research that—when accompanied by aligned market incentives—can bring to market effective therapies that address critical unmet needs.