Unlocking the potential of biomedical innovation: The crucial role the government and partnerships play in accelerating progress

Setting the stage: The biomedical ecosystem

The biomedical research ecosystem is composed of multiple stakeholders, all with an array of participants and contingencies for their existence and success. These stakeholders include sponsoring organizations (e.g., venture capital and startups), federal agencies, pharmaceutical companies, academic entities, philanthropic entities (e.g., NGOs), and patients and communities. The past decade has seen several forward-leaning efforts that harness the power of these various entities, from the passage of the 21st Century Cures Act by Congress in 2016,⁴ to the articulation of a Cancer Moonshot by President Obama overseen by then Vice President Biden,⁵ which continues under now President Biden, to a recent addition to the innovation roster—the creation of a new agency, ARPA-H.⁶

With increasing funding for novel, Moonshot-like research, government may be poised to be a key player in driving disruptive ecosystemwide solutions.

Three ways government and their partners can accelerate disruptive biomedical innovation

Government can work with partners to leverage the full continuum of relationships, prioritize patients and communities in the innovation pipeline, and support funding and collaboration infrastructure for last-mile innovations (figure 1).

1. Leverage the full continuum of collaboration to help foster innovation 

Even before the COVID-19 pandemic, partnerships that encouraged sharing of important assets, expertise, and knowledge, while aiming to reduce administrative red tape, were seemingly gaining ground. A number of federal agencies have been actively working to foster innovation through such partnerships. Examples include: the National Cancer Institute (NCI) Formulary, the NIH Pragmatic Trials Collaboratory, and several National Center for Advancing Translational Sciences (NCATS) programs (see the sidebar, “Prepandemic partnerships for innovation”).

During the COVID-19 pandemic, unprecedented collaborations were the bedrock of breakthrough innovation. It is important to “codify these lessons learned so as not to squander the many things the system discovered, and we need to see what was people-specific versus process-specific,” said one interviewee.¹² One such collaboration was the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) coordinated by the Foundation for the NIH (FNIH) and launched in April 2020 in the early days of the pandemic. ACTIV’s mission was to develop a research strategy for prioritizing and speeding development of the most-promising COVID-19 vaccines and therapeutics. It brought together multiple federal agencies, pharmaceutical companies, and representatives from academia, international agencies, and philanthropic entities.

ACTIV coordinated multiple clinical trials and reviewed many therapeutic compounds as well as shared its work through several scientific papers and presentations. Its spearheading role in the Countermeasures Acceleration Group (formerly known as Operation Warp Speed) can become a model for collaboration in the future of biomedical science.¹³ The incentives and mandates for collaboration outlined in the program led to vaccines being produced in record time and has been one of the most successful public-private partnerships in recent times.¹⁴

At the height of the pandemic, the entire ecosystem was focused on COVID-19 research and development, resulting in few competing priorities. Among the things that made the COVID-19 collaboration unique was the intensity of it: For example, 30–40 meetings a week at one point for one specific workstream.¹⁶ These sorts of partnerships are undeniably more demanding, and work best when partners have the resources and shared agenda that enable moving quickly. Though everyone under the tent had different perspectives, goals, and incentives, the end result was valuable for all partners: therapeutics and vaccines developed in record time.

When optimized, partnerships can save costs and time. “Partnerships put a structure around innovation,” said one interviewee, “and that is key.”¹⁷ Partnering for innovation can take myriad forms along the continuum of collaboration—from loose project-based collaboration with defined end dates, to alliances whose partnerships are ongoing and entail shared risks, responsibilities, and rewards, as well as many forms in between.

While networking and information-sharing can be considered a type of short-form partnership, collaboration, consortia formation, joint ventures, and strategic partnerships generally require a greater level of commitment and an extended time horizon for partnering, depending on the goal for which the partners decide to collaborate.

Ensure partners have time and resources. Keys to success include identifying the right players and having members play the right roles, all with a clear sense of goals, objectives, and timing.¹⁸ An interviewee recommended viewing the agencies as an asset in that they can provide “connector pieces to smooth handoffs.”¹⁹ For example, a federal health agency focused on health care may have an opinion on the way trials are designed, and the age of the cohort as decisions get made about reimbursement downstream. Assessing agency roles in advance would also be helpful, so each agency is aware of the unique role it plays beyond the individual representative.

Ensuring the group is optimized with support is also important, so it doesn’t fall completely on consortia members to shoulder all of the work. Among the challenges to avoid is “consortia fatigue,” a term defined several years back by the nonprofit FasterCures in its work defining the consortia space and culminating in a “consortia-pedia” catalogue of partnerships.²⁰ There is a strong need for cross-fertilization from different federal agencies on these partnerships. One interview also raised the specter of control, and how being in a partnership de facto means absolute control over outcomes is not possible. Moreover, as partners’ time continues to be diluted with other priorities, it may become challenging to secure commitments from all stakeholders.

Focus on ecosystemwide problems. For partnerships to drive innovation, the collaboration work should fit into partners’ existing workflows. Project-specific collaborations may not align well with all parties’ goals, while competing incentives may limit participation. Tackling an ecosystemwide problem area has the benefit of incentivizing all actors, and the power to unstick the research and development pipeline. Defined end dates for collaboration can also help partners visualize goals and stay focused and engaged.

Support academic space for innovation. Academic research partners face increasing challenges to generate novel innovation, representing a likely STEM talent gap in the future. As one interviewee described, “There is a progressive erosion of commitment to the academic side of the mission, which is driven by increasing health care costs, time dependence to care, a need to maintain fiscally viable outputs, less time to work on research interests, and less margin to apply to research infrastructure. These challenges limit the ability of the enterprise to ask challenging research questions and turns off interest in young, talented people who find it too hard to pursue a career in academic biomedical research.”²¹ Programs like ARPA-H can help bridge this gap by enabling fail-fast, fail-often research infrastructure, but more investments could help provide researchers the time, space, and aligned incentives to generate novel innovation into the future.

Dissolve silos that discourage collaboration. Having relationships in place from the start can foster effective partnerships—otherwise, when a crisis arises, leaders can waste valuable time building rapport, which can delay effective response.²³ But paradoxically, partnering can also hinder progress when partners can’t agree and when many opinions need to be considered before action can happen.

Sometimes partnerships are the right vehicle for innovation but the partners themselves are the obstacle. In some cases, organizations don’t want to work together no matter how much science is needed, so the field can’t deliver what’s needed. Acknowledging this issue can allow leaders to pinpoint potential solutions and track opportunities to break open previously closed research spaces. The Cancer Moonshot initiative exemplifies this by going beyond procuring funding to breaking down silos.²⁴ One of the explicit goals of the program initially was to dissolve academic and organizational silos so that the collective network formed is greater than the sum of its parts.²⁵ A number of programs under this initiative, like the My Pediatric and Adult Rare Tumor Network (MyPART) and Cancer Moonshot Bank, focus on patient participation to provide education, improve outcomes, share information, and in turn empower patients.²⁶

To leverage lessons learned, measure collaboration progress and impact. Though many leaders in the field have offered perspectives on the most important ingredients of unprecedented collaborations that helped with COVID-19 breakthroughs, more formal evaluation measures could help with understanding leading practices and impact.

To start, leaders can identify two to three elements of partnership to study for elements of success, replicating what works. Over time, partnerships can develop more formal evaluation frameworks, potentially leveraging continuous quality improvement methods. These methods would allow leaders to continuously measure progress and refine the approach to partnering for innovation in real time, improving results. The approach can also help optimize future collaborations by identifying success factors that can carry forward to future efforts.

2. Prioritize patients and communities in the innovation pipeline

Problems that involve multiple stakeholders across the ecosystem can be addressed through a co-creation process, in which stakeholders share responsibility for the problem and work together to solve it.²⁹ Recent years have seen a growing recognition of the importance of patient and community perspectives to improve the efficiency and effectiveness of the research process, though much work remains to be done.³⁰ As one interviewee described, “We tell people what we can measure, not ask what we should measure.”³¹

Elevate the patient voice. A number of recent efforts have made progress in incorporating consumer and patient voices in the process. The NIH Community Engagement Alliance (CEAL) engages people to address the disproportionate impact of COVID-19 on underserved communities. The program collaborates with local community organizations to develop deeply tailored messaging and interventions suited to different cultural contexts.³² By such direct partnering with community and patients, agency leaders can work to rebuild trust and improve the quality and relevance of innovation.

The Clinical and Translational Science Award (CTSA) program led by NCATS identified the need to engage patients and communities in research, and to involve them in all stages of the research process.³³ Many CTSA institutions have established Patient and Community Advisory Boards (PCABs) to provide input and guidance on research projects. These boards typically include patients, caregivers, and community members who have experience with the health condition being studied.³⁴

The development of the Patient-Centered Outcomes Research Institute (PCORI) is another example of attention to patient-centered innovation in the United States.³⁵ Established under the Affordable Care Act in 2010, PCORI funds research focuses on patient-centered outcomes. One such research program was the Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) trial studying prevention of heart attacks and strokes in patients with heart disease.³⁶ What made this trial unique is that it was designed with extensive input from patients (recruiting over 15,000) and their caregivers. Participants joined committee meetings, working group calls, and local and national awareness events, and provided input on the study portal and materials.³⁷ PCORI has served as a model for bringing patients and caregivers into the fold, but much more can be done to incorporate patient voices and priorities.

Design for equity. While involving patients and communities in the innovation pipeline is important, it is also important for benefits of innovation to be equitably distributed. This means designing and funding research that considers not just the return on innovation to industry but also the social returns on innovation. Health equity should be baked into the research design from the start, ensuring that new products are accessible to all who could benefit from them, especially marginalized, vulnerable, and high-need groups.

A community-centric approach is increasingly becoming essential to biomedical research, with recent federal legislation requiring all trials to include a diversity action plan.³⁹ The Community Based Participatory Research Program (CBPR)⁴⁰ by the NIH recognizes the unique expertise that communities possess and proffers a model for partnering with communities to increase research impact. Community partners are given equal decision-making power as scientists, from development to solution, in hopes of instilling greater trust between partners and producing better health outcomes.⁴¹

The All of Us Research Program,⁴³ launched in 2018 by the NIH, aims to enroll at least one million participants from diverse communities across the United States to gather data that can help improve health care for all—the program is over 50% of the way there.⁴⁴ By including individuals from diverse communities, the program aims to generate evidence that is more relevant and applicable to all patients. Such partnerships in biomedical innovation can drive an upstream health equity approach by addressing major treatment inequities and social, environmental, and economic drivers of those inequities.

Patient-centricity and community collaboration can increase trust in the scientific process, may lead to more relevant and impactful outcomes, and it is a global movement.⁴⁵ The European Patients’ Academy on Therapeutic Innovation (EUPATI)⁴⁶ and The Helix Centre⁴⁷ advocate for patient perspectives to be considered throughout the process and for patients to become more involved in the development of new medicines.⁴⁸

Lay the groundwork to make cocreation routine. To truly understand patient and community expectations through new innovations, both groups should be part of the dialogue from the start as partners. The federal government players should also be mindful that there is no one-size-fits-all approach, even within a specific patient population. This involves more than seeking cursory patient input about whether they’ll use a product or technology, for example. Rather, patients and their families can codesign research questions, and communities can articulate priorities, aiming to make the innovation pipeline both equitable and well suited to real problems on the ground.

One need look no farther for insights and ideas than the robust community of health nonprofits, leading the way with a focus and dedication to meeting their patient populations’ needs. These groups tend to handle issues across the full innovation continuum, including uptake and use by the community after approval and access via reimbursement.

Those interviewed all cited more need to include patients in discussions and process mapping, as well as needing to pass the baton across agencies to hasten decision-making and problem-solving when it comes to access. As one interviewee said, “Government has the power to bring agencies together, but it also has to have teeth and coordination. It can be the innovation engine for therapies.”⁴⁹ This harkens back to what we witnessed during the pandemic, a unifocus on solving the problem. “For a patient, time is not neutral,” cited one interviewee.⁵⁰ An exciting place to start fresh is including the patient and community voice in ARPA-H, at scale. A Patient Advisory Council would be a novel way to incorporate real-time input into the processes being developed and would provide scale for the organization.

3. Implement last-mile infrastructure to support high-risk research endeavors

Government is uniquely suited to tackle big problems because of the volume of funding and diversity of programs it supports to advance discoveries into human trials that have the highest possible chance of success in terms of both safety and efficacy. An interviewee explained, “We saw a challenge that government innovation can aim to solve: NCATS studies over 10,000 diseases, but 95% of diseases don’t have a therapy. Can we develop tools that apply to all 10,000+ diseases?”⁵¹

The literal last mile of translational research, the delivery of therapeutics and devices to the bedside for those diseases, is one of the hardest steps for any innovative idea. It typically requires a truly jaw-dropping number of partnerships, expertise, and capital: in short, entire ecosystems. This area is more important than ever as funding in the private sector declines for commercialization.

And yet this space does not lend itself to a top-down process from federal government. A unique partnership of baton-passing is necessary for discoveries to be translated and commercialized to solve problems for patients, the ultimate customers. For example, pharmaceutical innovation is a critical factor in the development and commercialization of new therapies, and it is an important component of the ecosystem that the government needs to engage with to facilitate last-mile delivery. Yet, this industry has recorded the lowest projected average return on investment (ROI) of 1.2% in 2022 from 6.8% in 2021.⁵² There is also a gap in late-stage pipeline assets that would replace those that were commercialized in the previous years.⁵³ In such a situation, accelerated speed of partnerships between the government and the industry is crucial.

Historically, the government has funded basic biomedical research and provided incentives for innovation hubs and similar initiatives. But the pandemic has demanded new approaches to innovation. Government can contribute to the last mile of the research and development pipeline through three main mechanisms:

1. Quicken the pace of innovation with tools that apply across multiple diseases
   
2. Fund place-based innovation ecosystems
3. De-risk the commercialization process through incentives and subsidies

Quicken the pace of innovation. On the input side, government can begin to offer researchers the space to take bigger risks with programs such as ARPA-H as a counterpoint to the pace and intention of traditional NIH-funded research. ARPA-H becomes a mechanism to focus on breakthrough disruption areas to help them incubate, scale, and grow. The ethos of faster innovation also implies failing faster first, hopefully resulting in more novel ideas entering the last-mile commercialization pipeline. Eliminating the ideas likely to fail earlier in the process can also significantly reduce the overall cost of developing new products.

ARPA-H aims to create a culture of experimentation, embracing measured risk taking.⁵⁴ As the first dedicated funding infrastructure in the health sphere for researchers to take bigger risks, it offers immense promise to generate impact beyond what is possible in the current ecosystem, complementing the work of partners in biopharma, philanthropy, and academia. The agency is intended to elevate visionary research ideas from across the innovation continuum, spanning disciplines and industries. Rather than develop specific drugs for specific diseases, ARPA-H seeks to generate new capabilities and platform technologies. The newly created agency is heavily leveraging lessons from DARPA and Advanced Research Projects Agency–Energy (ARPA-E), while considering the complexities of the health sector.⁵⁵ While DARPA responds to defense needs, biomedical innovation requires coordinated action by public and private actors with differing incentives, and all research has implications for human health. The strategic focus areas outlined within ARPA-H are Health Science Futures, Scalable Solutions, Proactive Health, and Resilient Systems.⁵⁶

Already the leadership of ARPA-H is discussing adding new questions to The Heilmeier Catechism, a set of questions developed by DARPA to help agency leaders evaluate research proposals.⁵⁷ Additional question ideas include how an innovation will be impacted by cost and accessibility, what customer experience looks like, and whether the project could be misunderstood. It is important that ARPA-H program managers figure out “connector pieces” to the agencies that can help play key roles in approval and dissemination of any discovery.

As one interviewee shared, “the DARPA model works because the bureaucracy doesn’t slow the research.”⁵⁸ Another interviewee spoke of “the huge gaping holes for incentives to engage on reimbursement” and cited later-stage cost impacts to Medicare if patients don’t receive adequate care in their lifespan.⁵⁹ These points again highlight the importance of a holistic approach to discovery.

Fund place-based innovation ecosystems. There is a risk that new and exciting initiatives like ARPA-H can fall into systemic traps where typical funding models lie, such as directing funds to the most funded investigators or well-known institutions as well as the most funded research areas. The research environment also tends to cater to many of the same places and hubs of innovation, and ARPA-H leaders should take extra steps to fund a more diverse pool of researchers as is detailed in its mission. The pandemic accelerated new thinking and paradigms about where workforce can reside, and this will likely hold true for both staff and those funded by ARPA-H.

Innovation leading to bedside therapies rarely comes from single entities but rather local community-based ecosystems that leverage local players and infrastructure.⁶² For instance, Boston has both talent and infrastructure for biomedical innovation because of the interconnectedness of industry biopharma players, academic institutions, and health systems that lead to an abundance of startups in the biotech space. Novel, disruptive ideas helmed by such startups are nurtured by a supportive ecosystem.

Successful development is not just about the capital but also the talent at all levels, e.g., research, management, regulatory experts, and clinical research organizations to streamline the clinical development, among others. It is typically difficult for a single innovator or startup to check all these boxes, but can be even more difficult when the startup is located outside of a major metropolitan innovation hub.

Agencies can consider funding promising new investigators from diverse locations to let local innovation flourish and spread throughout the United States, creating novel innovation clusters. With a skilled workforce, specialized infrastructure, and supportive institutions, innovation clusters can blossom in new places.⁶³

De-risk research and development in cases of high-risk, high-expected social returns. Contrary to popular belief, government and nongovernmental institutional investment in biomedical areas do not reduce private spending on R&D.⁶⁵ In fact, private spending on pharmaceutical R&D has increased dramatically in recent years despite increased government investments.⁶⁶ The expected cost to develop a new drug is now estimated to range from a little less than US$1 billion to more than US$2 billion.⁶⁷

If government and partners are ambitious enough to tackle all 10,000+ diseases, at a commercial level there needs to be demand for therapies that may otherwise lack the market to bring industry peers to the table. Therefore, government’s ability to subsidize research and development in areas of unmet need can serve as a mechanism to drive input into the last-mile pipeline. Two mechanisms are key: push and pull incentives.⁶⁸

1. Push incentives reduce the cost of development by offering financial, tax, and technical incentives regardless of anticipated failure in the market.
   
2. Pull incentives reward developments already considered relevant in the market and scientifically viable by ensuring developers’ financial viability into the future, even in inefficient markets.

Studies have shown that governmental increases in basic biomedical research funding, a push incentive mechanism, tends to increase private funding in related disease areas.⁶⁹ Rationally, industry seems to find it difficult to spend outsized amounts on research generating knowledge that is not directly translatable to a product, while NIH funding for basic science uncovers many of the mechanisms such applications could then leverage. To adjust supply and demand for therapies that could aid in underfunded disease areas, the government could implement a variety of push-pull policies (Fig. 2).

As funding gets tighter in the private sector, “government funding is now gap funding” was the thought of one interviewee.⁷⁰ Additionally, the idea that ARPA-H program managers can essentially place bets was important to many we talked with. It can be uncomfortable to bet on something that may fail, especially when the track record will likely be assessed so closely. But for years those in innovation circles have discussed how the way to move forward is to know what works, and what does not. Many interviewed expressed hopes for ARPA-H to have both wins but also failures.

The way forward

Government can catalyze disruptive innovation that changes the world for the better. The challenge is to do so without the external pressures of a pandemic. There should be careful consideration of the factors that worked during crisis and how to leverage these for future scenarios, crisis or not.

Three major drivers of government’s success that can propel innovation forward were identified:

1. Optimized partnerships on a scale unmatched before: Key success factors for the future could be incentives for all players in the ecosystem to participate, continuously measuring progress and outcomes, and a central entity like FNIH to coordinate disparate groups
   
2. Patient- and community-centered solutions to inspire innovation toward some of the hardest-hitting issues facing those most in need
3. Last-mile funding infrastructure via programs such as ARPA-H that can boost novel but commercially fragile innovations to reach the marketplace.

Government has already made great strides in this direction, proving instrumental in responding to one of the biggest biomedical crises in human history and engendering truly disruptive innovation: catalyzing the development and deployment of mRNA vaccines for COVID-19. Progress continues. Breakthrough biomedical innovations are not only possible, but probable, with government’s investment in the right infrastructure and incentives for an ecosystem approach to solving for the toughest problems. And yet many pieces that helped lead to effective COVID-19 vaccines were there in advance of the pandemic, and the system was not completely able to assemble them until the crisis.

The question is: How can blind spots be both identified and reduced going forward to accelerate disruptive innovation?