Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

Institute vows to roll back growth in applied grant funding.

NIH’s National Institute of Neurological Disorders and Stroke (NINDS) is promising to get serious about reversing its sharp decline in basic research funding since 1997—and finally match years of rhetoric about valuing the study of fundamental questions as much as applied research with more tangible action along the lines of recent moves.

Between 1997 and 2012, NINDS expenditures on basic research as a fraction of its total competing research budget fell from 87% to 71. The spending was shifted to applied research, which more than doubled in proportion from 13% to 29%.

NINDS saw an even sharper drop when it honed in on funding for “basic/basic” research focused on understanding the nervous system but not on any disease. The subcategory’s share of NINDS’ research budget fell by nearly half, from 52% to 27%.

“Gaps in our understanding of how the healthy brain and nervous system function can form roadblocks to understanding dysfunction in disease. Supporting the basic studies to fill those gaps is a critical piece of the NIH and NINDS mission—and an area unlikely to find sustained investment from the private sector,” NINDS director Story C. Landis, Ph.D., wrote on NINDS’ blog.

In a separate message, Dr. Landis added a dramatic warning: “If the recent decline continues unabated, in 10 years or so, we might not have any fundamental basic research left in our portfolio.”

NINDS is undertaking several steps to counteract the basic research decline, Robert Finkelstein, Ph.D., director of the NINDS Division of Extramural Research, told GEN.

The first step has been to convey more interest in basic research. In addition to the blog post, NINDS recently revised its mission statement to reflect its interest in a research balance: “to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.”

“Second, we are making sure that investigators understand that basic-basic grant applications do at least as well in peer review as disease-related applications. Third, when choosing which grant applications with scores beyond the payline to fund, we are taking into consideration the importance of fundamental research. Finally, we are currently considering other strategies (e.g., initiatives) to promote basic research funding,” Dr. Finkelstein said.

The “payline” is the rank up to which an institute or center intends to fund the majority of applications.

Ruling out Priorities

One step NINDS won’t take, he added, is prioritizing areas of basic research for increased funding: “It is important that the institute allow the community to determine what the most promising areas of investigation should be.”

The institute may wish to revisit the issue of guidance, however, if the initiatives do not succeed in swaying researchers from the view expressed by one respondent to Dr. Landis’ blog post.

“Many neuroscientists attempting to conduct research into basic scientific questions related to how the brain develops and functions in the adult and in aging individuals feel that it is extremely difficult to receive a sufficient priority score from a scientific review group that is within the range for funding if the proposal is ‘basic-basic,’” Lawrence Kromer, Ph.D., of Georgetown University, posted April 9. “Part of this appears to be a ‘mind’ shift in reviewers (partly fostered by NIH) that if it is not obviously ‘translatable’ to clinical use then it really is not important or significant research.”

That view appears to reflect NIH’s elevation of translational science in recent years. A key example of that was director Francis S. Collins, M.D., Ph.D., championing the creation of the National Center for Advancing Translational Sciences (NCATS) in 2011 and winning funding for it each year since: “Clearly, we need to speed the pace at which we are turning discoveries into better health outcomes,” Dr. Collins said in 2012, launching an NCATS program where researchers pursue new uses for pharmaceutical compounds. Yet in testimony before Congress that year, he spoke of a balance: “Basic discovery and the development of therapies go hand-in-hand at NIH.”

NINDS’ stance against prioritizing areas of basic research echoes the consensus of a 2009 advisory panel that examined a 10% drop between 2003–08—from 67.6% in FY 2003 to 57.5% in FY 2008—in the proportion of the extramural budget awarded to the largest category of competing grants, investigator-initiated basic research R01 grants. The panel found the decline “disproportionate compared to other components of the Institute budget.”

“We think this is likely to reflect a more general decline in support for basic research at NINDS. This decline puts at risk the long-term success of the NINDS portfolio,” the panel warned. “We strongly recommend that NINDS act decisively to stabilize funding for investigator-initiated R01 research and for basic science.”

A year later, NINDS unveiled its Strategic Priorities and Principles, which committed the agency to a balance between basic and applied research, as well as a basic research effort that was “approximately equally divided between research on the normal development and working of the nervous system and research related to disease mechanisms.”

Raising the Payline

Dr. Finkelstein said NINDS followed up on the 2009 study with aggressive cost-saving that enabled the institute to increase its funding payline from 11th percentile in 2009 to 15th in 2012. “We succeeded in doing this despite the fact that our federal budget appropriations either remained flat or declined during this period,” he added.

For the current fiscal year, however, NINDS said its payline will be the 14th percentile, reflecting the completion of several large research programs.

In addition to basic-research subgroups, the institute sorted applied funding grants into two subcategories—applied/translational funding for up to, but not including, first-in-human studies; and applied/clinical funding for first-in-human studies through Phase III trials.

Reasoning that a possible explanation for the jump in disease-focused spending was higher cost compared with basic, NINDS examined the number of awards issued, and found similar trends despite an increase in R01 awards.

NINDS also analyzed grant applications for two specific years (2008 and 2011) to see if the growth of disease-focused and applied grants could be explained by changes in the numbers of applications submitted, or by differences in success rates among subcategories. Instead, Dr. Landis reported, NINDS saw a 21% drop in dollars requested for basic-basic research projects—while disease-focused basic requests increased 23%, applied-translational requests rose 42%, and applied-clinical requests jumped 38%.

Despite the differences, funding rates remained stable over the same time period. In both 2008 and 2011, 26% of basic-basic applications won funding, highest of any of the subcategories—though the basic/disease-related grant funding rate inched up from 20% to 22%.

“Traditionally, NINDS has spent a greater proportion of its budget than many institutes on basic research,” Dr. Finkelstein cautioned, before offering another potential reason for NINDS’ high funding rate of basic-basic applications, a smaller stack of applications to choose from: “It is possible that basic researchers are continuing to apply for NIH funding, but are directing their applications to other NIH institutes that fund neuroscience.”

NINDS’ research into funding trends is valuable and should be replicated by each of NIH’s 26 other institutes and centers. That’s not likely to happen, unfortunately, since the agency’s FY2014 budget merely gained back much though not all of the funding lost to last year’s sequestration. That’s a shame, since a better-funded NIH can raise its success rates on all funding, including the basic research NINDS seeks to encourage.

Investigators will be eager to see if basic-basic rates eventually climb—and whether that increase is because of fewer applications, thus less chance of rejection, or because NINDS is truly eager to support research on fundamental questions. With overall R01 success rates falling from 30% in FY1997 to 17% in FY2013, researchers have been more inclined than ever to play it safe on their applications, which has helped disease and applied research projects at the expense of basic. Whether PIs continue that caution or pursue more basic research is a good question for a follow-up study from NINDS.

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