NINDS supports a broad range of research projects, from basic studies of the nervous system to large Phase III clinical trials. Several years ago, we embarked on an institute-wide planning process to analyze and optimize our investments in basic, translational, and clinical research. Triggered by the observation that between 2003 and 2008, NINDS funding for R01s decreased by 10%, we extended our analyses to determine how our extramural funds are distributed across the spectrum of basic and applied research, and whether that distribution has changed over time.
To perform the analysis, we developed simple definitions of basic and applied research (listed at the end of this post) that could be applied as unambiguously and reproducibly as possible. We also divided each of these broad categories into two subcategories—basic/basic, basic/disease-focused, applied/translational, and applied/clinical. Expert neuroscientists, including program directors, scientific review officers, and other members of our staff then assigned funded projects to these subcategories based on careful reading of abstracts, specific aims, and, when necessary, additional sections of the grant application. Because a single application often proposed research in more than one subcategory, we assigned percentages of a grant to each subcategory as appropriate; for example, a grant could be described as 75% basic/basic and 25% basic/disease-focused.
Our analysis covered the period between 1997 and 2012 to ensure that any trends we observed did not reflect a short-term response to a particularly good or bad funding year. This analysis included most of the new and competing continuation grants issued each year. The specific funding mechanisms that we included are described below. Since this was an extremely labor-intensive task (and our staff have day jobs!), we selected eight years within this period for review.
Our first finding was that between 1997 and 2012, NINDS expenditures on applied research as a fraction of total competing research budget increased from 13% to 29% while the proportion of basic research declined from 87% to 71% (Figure 1).
When we divided basic research into basic/basic and basic/disease-focused subcategories, we observed a striking decline in the funding of basic/basic research, which decreased from 52% to 27% of our competing budget during this time period (Figure 2).
One possible explanation for our increased spending on disease-focused research is that the cost of disease-focused research may have increased at a greater rate than that of fundamental basic research. We therefore examined the numbers of awards (as opposed to the dollars spent) in each broad category and subcategory, and found similar trends to those shown in Figures 1 and 2 (data not shown).
We also looked at the funding of basic/basic and disease-focused research specifically within the portion of the NINDS portfolio represented by investigator-initiated grants that were not solicited by the institute through targeted funding opportunity announcements (~70% in FY2012). Targeted solicitations are most often focused on filling scientific gaps in the Institute’s research portfolio related to understanding, preventing, or treating particular disorders or addressing public health concerns. By excluding applications submitted in response to these solicitations, we could assess the extent to which NINDS was driving the changes in relative funding of basic/basic and disease-focused grants. Figure 3 is analogous to Figure 2, but includes only investigator-initiated grants. The shift towards disease-focused research is less pronounced but still evident. While applications funded in response to NINDS solicitations tend to be disease-related or applied research, these data suggest that NINDS initiatives are not the major reason for the decline in basic/basic research funding.
What, then, is driving the overall NINDS shift from basic to applied research, and more specifically, the sharp decrease in fundamental basic research? If changes in the scientific landscape are driving this shift, then it could reflect a natural progression of the field, and NINDS certainly welcomes opportunities to translate basic discoveries into clinical applications. However, basic and applied research are necessarily intertwined and interdependent – basic discoveries lay the groundwork for clinical applications and applied investigations uncover new fundamental questions. We are therefore concerned by the alternative possibility that many investigators falsely believe that NINDS is no longer interested in supporting research into the normal function of the brain and nervous system, and that their chances of obtaining NIH funding are better if they propose disease-focused basic or applied studies, rather than fundamental basic science research. The current challenging budget environment and the growing number of NIH programs intended to accelerate translational research may be contributing to this belief. Comments from grant reviewers that question the relevance of proposed fundamental basic research projects to human disease could further reinforce the idea that a translational emphasis is advisable, if not required.
As a first step towards exploring this issue, we analyzed applications that were submitted during two specific years (2008 and 2011) for funding mechanisms included in the original analysis. We were interested in determining whether the trends shown above could be explained by changes in the numbers of applications submitted in the four subcategories or by differences in success rates among them. We found a striking decrease (- 21%) in dollars requested by PIs to support basic-basic research projects. In contrast, disease-focused basic requests increased 23%, applied-translational requests increased 42%, and applied-clinical requests increased 38%. However, Table 1 shows that despite these changes in application numbers, funding rates (Number of Funded Applications/Number of Total Applications) across categories remained quite stable over the same time period. Notably, fundamental basic science applications continue to perform as well, or better, in peer review than other applications.
My concern is that the decrease in the number of basic/basic applications reflects the perception that NINDS is only interested in disease-oriented research. NINDS is committed to maintaining a vibrant basic research enterprise. In fact, once we recognized the declining investment in basic/basic research, we began to emphasize fundamental basic science research in selecting high program priority grants for funding beyond the payline in 2012. As is evident from the last data point, our actions arrested its decline, at least temporarily.
We would like to understand better the decline in basic science applications. For example, why aren’t researchers submitting more fundamental basic research applications to NINDS? Are researchers sending these applications to other NIH neuroscience institutes, for example the National Institute of Mental Health (NIMH) or the National Institute on Drug Abuse (NIDA)? Are most of the newly-funded disease researchers former basic researchers, or do they represent a new cohort? We plan to continue to examine the causes for the decline, informed by the input received from this post and additional ongoing analyses.
Fundamental basic research is the engine of discovery; it generates new knowledge, drives innovation, and underlies all past and future breakthroughs. 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.
I believe that the most effective strategy for advancing scientific knowledge and translating that knowledge into therapies that benefit patients is to maintain a robust and balanced pipeline across the research spectrum – from fundamental basic research to large phase III clinical trials. This principle was articulated by Congress in the 2014 NIH appropriations bill. To that end, we recently revised our Institute’s mission statement to recognize the critical role of fundamental research while continuing to emphasize our commitment to enhancing health and reducing disability across the spectrum of neurological diseases and disorders. It now states: “The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease”.
I welcome any thoughts you have about how NINDS can work towards this goal.