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From page 167... ...
This chapter presents the committee's specific recommendations to better align investments in therapeutic development with disease burden and unmet need. Recognizing the complex, multisector landscape of thera peutic development, the committee identified several key areas for strategic action: public health data collation and availability, public investment in biomedical research, public–private partnerships, the regulatory environ ment, and payment and reimbursement policy incentives.
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From page 168... ...
168 ALIGNING INVESTMENTS IN THERAPEUTIC DEVELOPMENT Identify misalignments between: Problem Disease burden and Current therapeutic Definition unmet medical needs investments and scientific research efforts •Information gaps •Scientific gaps Key Barriers •Market failures to Alignment •Policy and regulatory frictions •Enhanced data transparency •Targeted research funding Policy Action •Policy and regulatory investment and reform Areas •Public–private partnerships •Increased research activity in high-need disease areas Intermediate •Reduction in scientific and market barriers Outcomes to innovation •Need-aligned therapeutic development that promotes equitable health benefits •Alignment of therapeutic innovation with public health priorities Long-Term •Improved health outcomes and health equity Outcomes •Enhanced return on health research and development investments FIGURE 6-1 Conceptual framework work aligning investment with therapeutic need.
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From page 169... ...
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.
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From page 170... ...
Instead, providing accessible 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 prioritize diseases with high population burden or high health disparities.
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From page 171... ...
There has been recent reporting about critical datasets and web pages being pulled from federal health websites, some of which is back online but with key data missing; such missing information damages scientists' ability to advance their research (Stone and Huang, 2025)
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From page 172... ...
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.
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From page 173... ...
treatment exists but is limited in its ability to address disease burden, overall or for specific at-risk subgroups of the population; (c) effective treatment exists, but access is limited: and (d)
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From page 174... ...
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. An approach for incentivizing the collection of these data would be to delay public access for a period of time (e.g., 6 months)
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From page 175... ...
programs by prioritizing higherrisk, potentially revolutionary ventures that could address unmet needs and prioritize therapeutic development sources that are not covered by other investment sources. Furthermore, recognizing that NIH staff, such as the Council of Councils, is closer to understanding how unmet needs could be met with research funding, there should be some funding that they have discretion to allocate, with consideration for disease burden and unmet need.
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From page 176... ...
c. Public and private funders should allocate funds for the develop ment and validation of new biomarkers and surrogate endpoints for diseases with high unmet medical need.
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From page 177... ...
, the National Cancer Institute Experimental Therapeutics (NExT) program, and Bridging Interventional Development Gaps (BrIDGs)
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From page 178... ...
Therefore, despite the potential for diagnostics to address unmet needs and to facilitate accurate diagnosis for drug development for unmet health needs, incentives to innovate in this space are lacking. As a result, the committee believes that PPPs could be one way to develop better diagnostics, such as for some elements of generating evidence supportive of patient access.
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From page 179... ...
Conclusion 5-1: Diagnostics to characterize and detect disease states are critical for developing innovative therapies, targeting therapeutics to those who will benefit, and ensuring that patients have access to therapeutics early enough in their disease progression for therapeutics to be effective, and they are an important component of addressing unmet clinical need. Further incentives for development of innovative and accurate diagnostic tests that are necessary for drugs that address unmet medical needs could help resolve the mismatch among therapeu tic investment, disease burden, and unmet need.
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From page 180... ...
Although the purpose of this specific PPP is to expedite investigator access to therapeutics in clinical trials and not necessarily to host a list of searchable assets, the success of the NCI Formulary could lay the groundwork for a more generalized searchable repository.
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From page 181... ...
The clinical trial infrastructure set up by NIH institutes involves academic researchers and institutions in addition to government. This can cause even more complex disagreements over IP between government, company, and academic institution policies being in conflict and creating a barrier to setting up effective PPPs due to the necessary complex negotiations.
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From page 182... ...
efforts to encourage investment to address unmet need; (2) efforts to address broad scientific
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From page 183... ...
As for the second category of FDA programs that address broad scientific challenges, improve coordination, and encourage data generation to address unmet needs, many of these programs are pilot programs or have only been in place for a short time. Therefore, there is not yet sufficient evidence to recommend expansion of these programs.
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From page 184... ...
In addition to timely completion of confirmatory studies following accelerated approval, it is also important to ensure that accelerated approval is granted only when drugs truly are reasonably likely to demonstrate clinical benefit (i.e., based on appropriate surrogate endpoints) , that confirmatory studies are rigorously designed in addition to being completed on time, and that drugs whose studies fail to clearly confirm clinical benefit
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From page 185... ...
. Although FDORA included provisions to require that key confirmatory study design parameters be established no later than the point of accelerated approval and to potentially expedite withdrawal proceedings when initiated by FDA, neither the law nor subsequent FDA guidance has sufficiently clarified the level of appropriate flexibility in accepting new surrogate endpoints to support accelerated approval, addressed poor rigor in confirmatory study design, or addressed FDA's response when confirmatory studies fail to clearly demonstrate a drug's clinical benefit.
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From page 186... ...
As discussed in Chapter 5, FDA regulatory flexibility can include approval based on a single pivotal study, acceptance of single arm trials, acceptance of poor surrogate endpoints for accelerated approval, acceptance of surrogate endpoints outside accelerated approval, and approval despite trials missing prespecified endpoints, among other flexibilities. FDA acknowledges that for serious diseases, the agency may accept weaker trial designs and endpoints, fewer trials, or less statistical confidence, pointing to perceived patient "willingness to accept less certainty about effectiveness in return for earlier access to much needed medicines" (FDA, 2019)
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From page 187... ...
Finding 5-8: Given the remaining unmet need, FDA is under pressure to increase regulatory flexibility beyond current approaches. Conclusion 5-6: When traditional approval standards cannot be sat isfied for scientific reasons, regulatory flexibility can be appropriate as long as the initial approval is based on a reasonable likelihood of clinical benefit and clinical benefit is rigorously and rapidly confirmed following approval.
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From page 188... ...
When FDA exercises flexibility, whether through accelerated approval or outside that pathway, the agency should require rigorous, timely confirmatory studies. As discussed earlier in Chapter 5, FDA has a number of efforts underway to encourage investment to address unmet needs; to address broad scientific challenges, improve coordination, and encourage data generation to address unmet needs; and to facilitate and expedite development, review, and approval to address unmet needs.
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From page 189... ...
GOAL 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 The current U.S. drug pricing and reimbursement system creates strong incentives for innovation -- particularly for novel therapies addressing unmet needs -- but, at the same time, it may perpetuate inequitable access to effective treatments.
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From page 190... ...
Reforming reimbursement policy and incentivizing innovation to address unmet needs requires grappling with the definition and value assessment of unmet need. Value-based pricing can be implemented through different approaches, which need not be directly linked to unmet need.
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From page 191... ...
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.
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From page 192... ...
, it is imperative to improve market access for these novel therapies that aim to address unmet needs. 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 (Phares et al., 2024)
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From page 193... ...
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.
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From page 194... ...
2019. Assessment of the clinical benefit of cancer drugs receiving accelerated approval.
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From page 195... ...
2021. Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: Retrospective observational study.
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From page 196... ...
2022. Medicaid and accelerated approval: Spending on drugs with and without proven clinical benefits.
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