The National Institutes of Health (NIH) funds some of the world’s most innovative biomedical research, but rising administrative burden and extended wait times—even in crisis—have shown that its funding system is in desperate need of modernization. Examples of promising alternative models exist: in the last two years, private “fast science funding” initiatives such as Fast Grants and Impetus Grants have delivered breakthroughs in responding to the coronavirus pandemic and aging research on days to one-month timelines, significantly faster than the yearly NIH funding cycles. In response to the COVID-19 pandemic the NIH implemented a temporary fast funding program called RADx, indicating a willingness to adopt such practices during acute crises. Research on other critical health challenges like aging, the opioid epidemic, and pandemic preparedness deserves similar urgency. We therefore believe it is critical that the NIH formalize and expand its institutional capacity for rapid funding of high-potential research.
Using the learnings of these fast funding programs, this memo proposes actions that the NIH could take to accelerate research outcomes and reduce administrative burden. Specifically, the NIH director should consider pursuing one of the following approaches to integrate faster funding mechanisms into its extramural research programs:
- Reform the existing R21 grant mechanism to bring it more in line with its own goals of funding high-reward, rapid-turnaround research; and
- Direct NIH institutes and centers to independently develop and deploy new research programs with faster funding timelines.
Future efforts by the NIH and other federal policymakers to respond to crises like the COVID-19 pandemic would also benefit from a clearer understanding of the impact of the decision-making process and actions taken by the NIH during the earliest weeks of the pandemic. To that end, we also recommend that Congress initiate a report from the Government Accountability Office to illuminate the outcomes and learnings of fast governmental programs during COVID-19, such as RADx.
Challenge and Opportunity
The urgency of the COVID-19 pandemic created adaptations not only in how we structure our daily lives but in how we develop therapeutics and fund science. Starting in 2020, the public saw a rapid emergence of nongovernmental programs like Fast Grants, Impetus Grants, and Reproductive Grants to fund both big clinical trials and proof-of-concept scientific studies within timelines that were previously thought to be impossible. Within the government, the NIH launched RADx, a program for the rapid development of coronavirus diagnostics with significantly accelerated approval timelines. Though the sudden onset of the pandemic was unique, we believe that an array of other biomedical crises deserve the same sense of urgency and innovation. It is therefore vital that the new NIH director permanently integrate fast funding programs like RADx into the NIH in order to better respond to these crises and accelerate research progress for the future.
To demonstrate why, we must remember that the coronavirus is far from being an outlier—in the last 20 years, humanity has gone through several major pandemics, notably swine flu, SARS CoV-1, and Ebola. Based on the long-observed history of infectious diseases, the risk of pandemics with an impact similar to that of COVID-19 is about two percent in any year. An extension of naturally occurring pandemics is the ongoing epidemic of opioid use and addiction. The rapidly changing landscape of opioid use—with overdose rates growing rapidly and synthetic opioid formulations becoming more common—makes slow, incremental grantmaking ill-suited for the task. The counterfactual impact of providing some awards via faster funding mechanisms in these cases is self-evident: having tests, trials, and interventions earlier saves lives and saves money, without sacrificing additional resources.
Beyond acute crises, there are strong longer-term public health motivations for achieving faster funding of science. In about 10 years, the United States will have more seniors (people aged 65+) than children. This will place substantial stress on the U.S. healthcare system, especially given that two-thirds of seniors suffer from more than one chronic disease. New disease treatments may help, but it often takes years to translate the results of basic research into approved drugs. The idiosyncrasies of drug discovery and clinical trials make them difficult to accelerate at scale, but we can reliably accelerate drug timelines on the front end by reducing the time researchers spend in writing and reviewing grants—potentially easing the long-term stress on U.S. healthcare.
The existing science funding system developed over time with the best intentions, but for a variety of reasons—partly because the supply of federal dollars has not kept up with demand—administrative requirements have become a major challenge for many researchers. According to surveys, working scientists now spend 44% of their research time on administrative activities and compliance, with roughly half of that time spent on pre-award activities. Over 60% of scientists say administrative burden compromises research productivity, and many fear it discourages students from pursuing science careers. In addition, the wait for funding can be extensive: one of the major NIH grants, R01, takes more than three months to write and around 8–20 months to receive (see FAQ). Even proof-of-concept ideas face onerous review processes and take at least a year to fund. This can bottleneck potentially transformative ideas, as with Katalin Kariko famously struggling to get funding for her breakthrough mRNA vaccine work when it was at its early stages. These issues have been of interest for science policymakers for more than two decades, but with little to show for it.
Though several nongovernmental organizations have attempted to address this need, the model of private citizens continuously fundraising to enable fast science is neither sustainable nor substantial enough compared to the impact of the NIH. We believe that a coordinated governmental effort is needed to revitalize American research productivity and ensure a prompt response to national—and international—health challenges like naturally occurring pandemics and imminent demographic pressure from age-related diseases. The new NIH director has an opportunity to take bold action by making faster funding programs a priority under their leadership and a keystone of their legacy.
The government’s own track record with such programs gives grounds for optimism. In addition to the aforementioned RADx program at NIH, the National Science Foundation (NSF) runs the Early-Concept Grants for Exploratory Research (EAGER) and Rapid Response Research (RAPID) programs, which can have response times in a matter of weeks. Going back further in history, during World War II, the National Defense Research Committee maintained a one-week review process.
Faster grant review processes can be either integrated into existing grant programs or rolled out by institutes in temporary grant initiatives responding to pressing needs, as the RADx program was. For example, when faced with data falsification around the beta amyloid hypothesis, the National Institute of Aging (NIA) could leverage fast grant review infrastructure to quickly fund replication studies for key papers, without waiting for the next funding cycle. In case of threats to human health due to toxins, the National Institute of Environmental Health Sciences (NIEHS) could rapidly fund studies on risk assessment and prevention, giving public evidence-based recommendations with no delay. Finally, empowering the National Institute of Allergy and Infectious Diseases (NIAID) to quickly fund science would prepare us for many yet-to-come pandemics.
Plan of Action
The NIH is a decentralized organization, with institutes and centers (ICs) that each have their own mission and focus areas. While the NIH Office of the Director sets general policies and guidelines for research grants, individual ICs have the authority to create their own grant programs and define their goals and scope. The Center for Scientific Review (CSR) is responsible for the peer review process used to review grants across the NIH and recently published new guidelines to simplify the review criteria. Given this organizational structure, we propose that the NIH Office of the Director, particularly the Office of Extramural Research, assess opportunities for both NIH-wide and institute-specific fast funding mechanisms and direct the CSR, institutes, and centers to produce proposed plans for fast funding mechanisms within one year. The Director’s Office should consider the following approaches.
Approach 1. Develop an expedited peer review process for the existing R21 grant mechanism to bring it more in line with the NIH’s own goals of funding high-reward, rapid-turnaround research.
The R21 program is designed to support high-risk, high-reward, rapid-turnaround, proof-of-concept research. However, it has been historically less popular among applicants compared to the NIH’s traditional research mechanism, the R01. This is in part due to the fact that its application and review process is known to be only slightly less burdensome than the R01, despite providing less than half of the financial and temporal support. Therefore, reforming the application and peer review process for the R21 program to make it a fast grant–style award would both bring it more in line with its own goals and potentially make it more attractive to applicants.
All ICs follow identical yearly cycles for major grant programs like the R21, and the CSR centrally manages the peer review process for these grant applications. Thus, changes to the R21 grant review process must be spearheaded by the NIH director and coordinated in a centralized manner with all parties involved in the review process: the CSR, program directors and managers at the ICs, and the advisory councils at the ICs.
The track record of federal and private fast funding initiatives demonstrates that faster funding timelines can be feasible and successful (see FAQ). Among the key learnings and observations of public efforts that the NIH could implement are:
- Pilot monthly or bimonthly study section and advisory council meetings for R21 grant review. CSR has switched to conducting the majority of its meetings virtually since the COVID-19 pandemic and has found that in-person and virtual meetings are of equal quality. CSR should take advantage of the convenience of virtual meetings by piloting shorter, virtual monthly or bimonthly study section meetings to review R21 grants outside of the three regular meetings held each year. By meeting more frequently but for shorter amounts of time, the individual time commitment for each meeting is reduced, which may incentivize more researchers to participate in study sections and prevent reviewer fatigue from the traditional one- to two-day meetings. To match this change, the advisory councils of ICs that review R21 grant applications should also pilot monthly virtual meetings, timed to occur immediately after the corresponding peer review meetings. Together, these changes could reduce the R21 grant review timeline from a minimum of nine months down to just two or three months.
- Explore new approaches for reviewer participation. One obstacle to faster funding timelines is the recruitment of reviewers without a conflict of interest. Previously, the travel and financial burden of in-person study sections kept the standing body of reviewers small; this makes it difficult to find and gather a quorum of knowledgeable and unconflicted experts. With online study sections, the CSR could engage a larger committee of reviewers at lower cost. This would allow them to identify and address conflicts of interest dynamically and to select a small and varying subset of reviewers to meet each month. Scientists may also be more inclined to participate as potential reviewers, knowing that they may not be called upon for every round of reviews.
- Emphasize the potential value of success over risk. Reviewers should be explicitly instructed not to lower their scores for the Approach criterion (or the new Rigor and Feasibility criterion proposed by CSR) solely due to a lack of extensive prior literature or over differences in the applicant’s past area of expertise. (Reviewer suggestions could still be used to help inform the direction of the proposed work in these cases.) Instead, the Significance and Innovation criteria (or the new Importance of Research criterion) should be weighed much more heavily than other criteria in the overall score. The rationale for these changes is evident: novel areas will naturally have less extensive prior literature, while learnings from one area of research can cross-pollinate innovation in an entirely different area of research. Acceptance of high-risk, high-reward proposals could be further facilitated by piloting the “golden ticket” model, in which reviewers are provided the right to unilaterally fund one application per year that they believe holds the most innovation potential.
- Reduce the length of applications. The length of proposals for both Fast Grants and Impetus Grants did not exceed two pages, which, according to reviewers, was more than enough to make well-reasoned judgment calls. The NIH should reduce the page limit from six to three pages for the R21 grant program. This will reduce the administrative burden and save time for both applicants and peer reviewers.
Pending the success of these changes, the NIH should consider applying similar changes to other major research grant programs.
Approach 2. Direct NIH institutes and centers to independently develop and deploy programs with faster funding timelines using Other Transaction Authority (OTA).
Compared to reforming an existing mechanism, the creation of institute-specific fast funding programs would allow for context-specific implementation and cross-institute comparison. This could be accomplished using OTA—the same authority used by the NIH to implement COVID-19 response programs. Since 2020, all ICs at the NIH have had this authority and may implement programs using OTA with approval from the director of NIH, though many have yet to make use of it.
As discussed previously, the NIA, NIDA, and NIAID would be prime candidates for the roll-out of faster funding. In particular, these new programs could focus on responding to time-sensitive research needs within each institute or center’s area of focus—such as health crises or replication of linchpin findings—that would provide large public benefits. To maintain this focus, these programs could restrict investigator-initiated applications and only issue funding opportunity announcements for areas of pressing need.
To enable faster peer review of applications, ICs should establish (a) new study section(s) within their Scientific Review Branch dedicated to rapid review, similar to how the RADx program had its own dedicated review committees. Reviewers who join these study sections would commit to short meetings on a monthly or bimonthly basis rather than meeting three times a year for one to two days as traditional study sections do. Additionally, as recommended above, these new programs should have a three-page limit on applications to reduce the administrative burden on both applicants and reviewers.
In this framework, we propose that the ICs be encouraged to direct at least one percent of their budget to establish new research programs with faster funding processes. We believe that even one percent of the annual budget is sufficient to launch initial fast grant programs funded through National Institutes. For example, the National Institute of Aging had an operating budget of $4 billion in the 2022 fiscal year. One percent of this budget would constitute $40 million for faster funding initiatives, which would be on the order of initial budgets of Impetus and Fast Grants ($25 million and $50 million accordingly).
NIH ICs should develop success criteria in advance of launching new fast funding programs. If the success criteria are met, they should gradually increase the budget and expand the scope of the program by allowing for investigator-initiated applications, making it a real alternative to R01 grants. A precedent for this type of grant program growth is the Maximizing Investigators’ Research Award (MIRA) (R35) grant program within the National Institute of General Medical Sciences (NIGMS), which set the goal of funding 60% of all R01 equivalent grants through MIRA by 2025. In the spirit of fast grants, we recommend setting a deadline on how long each institute can take to establish a fast grants program to ensure that the process does not extend for too many years.
Additional recommendation. Congress should initiate a Government Accountability Office report to illuminate the outcomes and learnings of governmental fast funding programs during COVID-19, such as RADx.
While a number of published papers cite RADx funding, the program’s overall impact and efficiency haven’t yet been assessed. We believe that the agency’s response during the pandemic isn’t yet well-understood but likely played an important role. Illuminating the learnings of these interventions would greatly benefit future emergency fast funding programs.
The NIH should become a reliable agent for quickly mobilizing funding to address emergencies and accelerating solutions for longer-term pressing issues. As present, no funding mechanisms within NIH or its branch institutes enable them to react to such matters rapidly. However, both public and governmental initiatives show that fast funding programs are not only possible but can also be extremely successful. Given this, we propose the creation of permanent fast grants programs within the NIH and its institutes based on learnings from past initiatives.
The changes proposed here are part of a larger effort from the scientific community to modernize and accelerate research funding across the U.S. government. In the current climate of rapidly advancing technology and increasing global challenges, it is more important than ever for U.S. agencies to stay at the forefront of science and innovation. A fast funding mechanism would enable the NIH to be more agile and responsive to the needs of the scientific community and would greatly benefit the public through the advancement of human health and safety.
The NIH released a number of Notices of Special Interest to allow emergency revision to existing grants (e.g., PA-20-135 and PA-18-591) and a quicker path for commercialization of life-saving COVID technologies (NOT-EB-20-008). Unfortunately, repurposing existing grants reportedly took several months, significantly delaying impactful research.
The current scientific review process in NIH involves multiple stakeholders. There are two stages of review at NIH, with the first stage being conducted by a Scientific Review Group that consists primarily of nonfederal scientists. Typically, Center for Scientific Review committees meet three times a year for one or two days. This way, the initial review starts only four months after the proposal submission. Special Emphasis Panel meetings that are not recurring take even longer due to panel recruitment and scheduling. The Institute and Center National Advisory Councils or Boards are responsible for the second stage of review, which usually happens after revision and appeals, taking the total timeline to approximately a year.
Because of the difficulty of empirically studying drivers of scientific impact, there has been little research evaluating peer review’s effects on scientific quality. A Cochrane systematic review from 2007 found no studies directly assessing review’s effects on scientific quality, and a recent Rand review of the literature in 2018 found a similar lack of empirical evidence. A few more recent studies have found modest associations between NIH peer review scores and research impact, suggesting that peer review may indeed successfully identify innovative projects. However, such a relationship still falls short of demonstrating that the current model of grant review reliably leads to better funding outcomes than alternative models. Additionally, some studies have demonstrated that the current model leads to variable and conservative assessments. Taken together, we think that experimentation with models of peer review that are less burdensome for applicants and reviewers is warranted.
Intuitively, it seems that having longer grant applications and longer review processes ensures that both researchers and reviewers expend great effort to address pitfalls and failure modes before research starts. However, systematic reviews of the literature have found that reducing the length and complexity of applications has minimal effects on funding decisions, suggesting that the quality of resulting science is unlikely to be affected.
Historical examples have also suggested that the quality of an endeavor is largely uncorrelated from its planning times. It took Moderna 45 days from COVID-19 genome publication to submit the mRNA-1273 vaccine to the NIH for use in its Phase 1 clinical study. Such examples exist within government too: during World War II, National Defense Research Committee set a record by reviewing and authorizing grants within one week, which led to DUKW, Project Pigeon, Proximity fuze, and Radar.
Recent fast grant initiatives have produced high-quality outcomes. With its short applications and next-day response times, Fast Grants enabled:
- detection of new concerning COVID-19 variants before other sources of funding became available.
- work that showed saliva-based COVID-19 tests can work just as well as those using nasopharyngeal swabs.
- drug-repurposing clinical trials, one of which identified a generic drug reducing hospitalization from COVID-19 by ~40%.
- Research into “Long COVID,” which is now being followed up with a clinical trial on the ability of COVID-19 vaccines to improve symptoms.
Impetus Grants focused on projects with longer timelines but led to a number of important preprints in less than a year from the moment person applied:
- Aging Fly Cell Atlas
- Modular, programmable RNA sensing using ADAR editing in living cells
- Mechanisms of natural rejuvenation in a test tube
- Optogenetic rejuvenation of mitochondrial membrane potential to extend C. elegans lifespan
- Evidence that conserved essential genes are enriched for pro-longevity factors
- Trials on neuroprotective effects of Canagliflozin
With the heavy toll that resource-intensive approaches to peer review take on the speed and innovative potential of science—and the early signs that fast grants lead to important and high-quality work—we feel that the evidentiary burden should be placed on current onerous methods rather than the proposed streamlined approaches. Without strong reason to believe that the status quo produces vastly improved science, we feel there is no reason to add years of grant writing and wait times to the process.
The adoption of faster funding mechanisms would indeed be valuable across a range of federal funding agencies. Here, we focus on the NIH because its budget for extramural research (over $30 billion per year) represents the single largest source of science funding in the United States. Additionally, the NIH’s umbrella of health and medical science includes many domains that would be well-served by faster research timelines for proof-of-concept studies—including pandemics, aging, opioid addiction, mental health, cancer, etc.
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