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    NIH funds more long-term grants

    The R35 and ESI MERIT awards offer researchers an opportunity to spend more time on science and less on applying for grants — and yet, not many scientists apply.

    Research working with petri dish in lab National Institutes of Health

    Like many researchers, Holly Prigerson, PhD, seemed to spend more time on grant applications than science. But in 2014, shortly after she was appointed the Irving Sherwood Wright Chair in Geriatrics at Weill Cornell Medicine in New York, she applied for the National Cancer Institute’s (NCI) Outstanding Investigator Award (R35). With the R35, researchers receive a single grant for more time—seven years in the case of NCI—than the project-based R01 grant, which typically lasts three to four years.

    “It has transformed my approach to doing research,” says Prigerson, who was part of the first group of 62 scientists to receive NCI’s R35. “It’s given me more time and more funding to actually do the science.”

    That’s a primary goal of the R35: To break the maddening cycle of applying and reapplying for grants. Both NCI’s R35 and the National Heart, Lung, and Blood Institute’s R35, which was introduced in 2016, support researchers’ work for seven years at a maximum of $600,000 in annual direct costs. The National Institute of General Medical Sciences’ (NIGMS) R35, called the Maximizing Investigators’ Research Award (MIRA), debuted in 2015. MIRA generally provides funding for five years, and applicants can request up to $750,000 in direct costs. The National Institute of Neurological Disorders and Stroke also offers an R35 award, and provides funding for eight years with a cap of $750,000.

    And yet, despite providing more stability, flexibility, and efficiency to the research process, the R35 is still an under-the-radar grant. In fiscal year 2017, the National Institutes of Health (NIH) reviewed 786 applications for R35 grants and approved 302 (a 38.4% success rate), compared to 27,169 R01 applications reviewed and 4,546 approved (a 16.7% success rate).

    Jon Lorsch, PhD, director of NIGMS, hopes to change that. “We'll be adding more and more grantees, and my hope is that it will accelerate,” he says.

    Long-time frustrations, long-term thinking

    Medical schools and teaching hospitals house some of the world’s most prominent research laboratories and employ hundreds of thousands of researchers whose work unlocks the secrets to our most complex medical mysteries, including cancer, heart disease, diabetes, and Alzheimer’s.

    More than half of all external research funded by the NIH is conducted by scientists at medical schools and teaching hospitals. The most common grant is the R01, which supports a “discrete, specified, circumscribed research project.” But the R01 is not designed to promote daring research.

    “An R01 is project-by-project funding, so it tends to emphasize short-term success,” says Ross McKinney, MD, AAMC chief scientific officer. It also has a time-wasting side effect. Soon after investigators hire staff and launch the project, they’re reapplying for funding. Principal investigators spent an astonishing 42% of their time on administrative tasks rather than research, a 2009 study by the Federal Demonstration Partnership found.

    Norman Sharpless, MD, director of NCI, has experienced the aggravations firsthand. As a scientist, he wrote more than 100 grant applications over 15 years, and most of his proposals were never funded. “I had a large grant go completely unreviewed because the application did not precisely comply with funding announcement guidelines,” he says. “These things are beyond exasperating, and I know how tough the process can be.”

    Enter the R35, which not only eases the grant application process, but encourages investigators to be more adventurous. “The R35 looks at your career arc and says, ‘This is a person who’s had good ideas,’” McKinney says. “’There may not be a specific project that’ll be a short-term win, but we want to fund this person’s work so that we all benefit from his or her creativity and scientific insights.’”

    The benefits of the R35

    In addition to reducing administrative burdens, the R35’s longer timespan offers multiple other upsides. Among them:

    • More flexibility. Unlike the narrow focus of the R01, the R35 provides researchers with the freedom to explore new concepts. “If they have a new idea that leads them in a different direction, they are free to follow that path as long as it is still within the mission,” says Lorsch. The R35 allowed Prigerson to pursue a variety of ideas, from studying family caregivers of cancer patients in the ICU to the difficulties faced by Latino Americans when receiving end-of-life care. The award, she says, has stimulated research that probably wouldn’t have occurred otherwise.
    • Increased risk-taking. With the R01, reviewers want a sure-to-succeed, low-risk proposition. “The less-creative research gets funded project-by-project because you have the preliminary data that says it’s likely to work,” says McKinney. The R35’s longer timeline encourages less-predictable options. “It helps you to think big and broadly about the problem you have been studying and to see the issue from new perspectives—to stop playing research whack-a-mole with the daily to-do’s that arise and consider other possibilities,” Prigerson says.
    • Greater stability. The longer timeframe can reduce uncertainty, but NIGMS also wants to provide researchers with stability during the renewal process. As an example, consider an applicant who does not receive the absolute top score yet still has a meritorious application. “Rather than just say, ‘Sorry, we’re not going to fund your grant, you'll have to try again,’ we’ll be able to fund them at a reduced level,” says Lorsch. “That way they can continue their program but ramp it down to a somewhat smaller scale. We heard a lot of people say they would prefer that to, ‘You did well, but sorry, you're not funded,’ which is the way things currently happen with an R01.”

    The trade-offs

    In exchange for the program’s multiple upsides, researchers’ overall funding is reduced. For NIGMS grantees, the average cut is about 12%. For the NCI R35, awardees receive about the same amount of funding, but over a longer period, notes Sharpless.

    Because NCI is targeting its R35 toward a more elite group of “investigators with outstanding records of productivity in cancer research,” the agency awards only about 15 to 20 new R35 grants each year. However, if there’s a significant increase or decrease in applications, it will reconsider the number of annual grants, Sharpless says.

    At NIGMS, one of Lorsch’s goals is to increase the number of highly meritorious investigators funded by MIRA. Remember that 12% average cut to the budgets of R35 grantees? “That money goes back into the pool,” says Lorsch. “It allows us to fund additional investigators, and to increase the support for the average investigator who has a MIRA grant, bringing the median direct cost to about $250,000.”

    Many researchers believe that the R35’s upsides outweigh the downsides. Daniel Lew, PhD, who is conducting research on cell polarity and symmetry breaking at Duke University, had two and a half R01 grants before obtaining the MIRA in 2017. “The R35 consolidates funding and gives me more freedom to pursue what I find most interesting, and to be judged by overall progress,” he says. “Having fewer grants to write and a longer timeframe were attractive enough to offset the anticipated 12% cut in overall funding.”

    Assisting young scientists

    Agencies like NCI also want to boost the work of less-established researchers. Sharpless has directed NCI divisions and centers to increase first R01s awarded to early-stage investigators (ESIs) by at least 25% in the next fiscal year. And in early 2018, NCI began offering the Method to Extend Research in Time (MERIT) Award, which provides seven years of funding—and does not require awardees to give up other awards. ESIs who receive an R01 will also be eligible to transition to the MERIT.

    “Not every young investigator who gets an R01 is guaranteed to have it transitioned,” says Sharpless. “But we are committed to helping as many of these early career scientists as we can.”

    At NIGMS, the MIRA also includes the Early Stage Investigator (ESI) Award: A grant aimed at principal investigators who earned their PhD or completed their medical residency less than 10 years earlier, and who haven’t received an R01-equivalent grant. MIRA awards ESI grantees up to $250,000 annually in direct costs for five years. Another bonus? The application is six pages, compared to 12 for the R01. Since the MIRA program started in 2015, ESI applications have increased by 60%.

    “The sections are more open-ended—what is your big picture plan? What have you done so far? What do you want to do? That format allows you to think more in terms of the big picture,” says Keary M. Engle, PhD, 31, who received a five-year, $1.25 million MIRA grant in August 2017 to study molecule-building techniques at The Scripps Research Institute.

    Sharpless admits that these new grants won’t magically address every challenge faced by researchers who seek stable funding for their work. But he believes the R35 meets a need and will improve awardees’ productivity. “I see grants with longer award lengths, and that consolidate existing grants to a smaller number of awards, as good places to start,” he says.

    As for Prigerson, she has seen few significant downsides to the R35. “This isn’t like winning the lottery and then learning that taxes deplete much of the winnings,” she says. “It has been almost universally good for me, my research program, and my mentees.”