Author: Jon Lorsch

As part of an ongoing examination of our grant portfolio to ensure that we invest taxpayer money as effectively and efficiently as possible, we recently analyzed changes over time in the distribution of investigator-initiated research compared to research funded through targeted funding opportunity announcements (FOAs).

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Changes over time in NIGMS investments in investigator-initiated research (research grant funds not associated with targeted FOAs) (right axis) and research funded through targeted FOAs (left axis). The analysis does not include fellowship, career development and training awards; programs transferred to NIGMS from the former National Center for Research Resources; and some other programs. For more details about the analysis, which was performed by Jim Deatherage, chief of our Cell Biology Branch, see the NIGMS Funding Trends Web page.

The figure shows that in the early 1990s, 99% of NIGMS’ grant budget supported investigator-initiated research, compared to 80% today. During the budget doubling in Fiscal Years 1998-2003, the Institute’s investment in research funded through targeted FOAs increased dramatically, then continued to increase at a slower rate during Fiscal Years 2004-2009.

As I discussed in a previous post about our large-scale research initiatives and centers, there were many good reasons for using FOAs to target specific areas of research with some of the funds made available by the budget doubling. For example, FOAs allowed the Institute to experiment with catalyzing the development of such new and emerging fields as structural genomics, pharmacogenomics and systems biology.

Since the budget doubling ended, however, maintaining steady support for our targeted research portfolio has made it difficult to maintain steady support for investigator-initiated research project grants (RPGs). Partly as a result, the success rate for RPGs (the number of funded RPGs divided by the number of RPG applications) fell below 20% in Fiscal Year 2013. Although a number of factors have contributed to the declining success rate, a significant one is that targeted and investigator-initiated research grants compete directly with each other. To bolster the success rate, we need to decrease our commitment to targeted FOAs. Furthermore, because none of us knows where the next major advances will arise, the soundest investment strategy is to have a distributed portfolio in which researchers investigate a wide range of scientific questions. History strongly suggests that letting scientists “follow their noses”—which involves a combination of curiosity, expertise, creativity and serendipity—is the most productive route to findings that will eventually translate into medical and technological breakthroughs.

To rebalance our portfolio in order to renew and reinvigorate our commitment to investigator-initiated research, we will be reducing our use of targeted FOAs, generally reserving them for cases in which they are likely to have a major impact on a large segment of the biomedical research enterprise. These cases could include promoting the rapid development of accessible, cost-effective new technologies that enable major advances in understanding biological systems; more efficiently organizing the Nation’s basic biomedical research resources to provide scientists throughout the country access to high-end instrumentation and technical expertise; and, in some instances, using targeted FOAs with defined lifetimes to catalyze the rapid development of emerging research areas.

It is important to note that we are making a distinction between investigator-initiated research and targeted research, not between investigator-initiated research and team science. We strongly support team science, which can certainly be investigator-initiated, and we expect such collaborative efforts to increase as research probes more deeply into the complexities of living systems. Currently, team-based, investigator-initiated research can be funded through multi-PI R01s and can also occur through groups of individually funded PIs working together. In special cases, program project grants (P01s) may be appropriate, particularly for long-term, interdisciplinary collaborations that require dedicated core facilities. As we move forward with our strategic planning process, we will be exploring additional ways to support investigator-initiated team science. I invite you to send us ideas you have for how best to do this.

On October 16, Congress passed a continuing resolution to fund the Federal Government through January 15, 2014, at Fiscal Year 2013 levels. This short-term budget allows us to begin funding some of the grant applications approved by our Advisory Council in September. However, because the funds we have available are only for a fraction of the fiscal year and we don’t know what the budget for the rest of the year will be, we need to be conservative in our funding decisions until a longer-term budget is approved.

Led by NIGMS Acting Deputy Director Judith Greenberg, the directors of the NIGMS scientific divisions developed principles to help us decide which of the many outstanding applications we are considering should receive funding now and which should be deferred for later start dates, if sufficient funds become available after January 15.

The fundamental question the division directors addressed was which categories of investigators would face the most serious jeopardy from a delay in funding. Based on the group’s careful deliberations, we will give priority to highly rated applications from investigators who have little or no current support from any source. Within this category, we will generally give priority to competing renewal applications over new applications, although in each case, we will take into account the particular circumstances of the investigator and her/his laboratory. For instance, an application from an early stage investigator who has been a tenure-track faculty member for 4 years, has exhausted all start-up funds and has no additional sources of funding would be considered a high priority.

We recognize that a delay in funding presents challenges for every investigator, but we hope you understand that our top priority in these difficult fiscal times must be to ensure the health of the overall biomedical research enterprise in the United States. Keeping productive and promising labs open is an essential element of this goal.

There have been a lot of discussions lately at NIGMS about large-scale research initiatives and centers. In these conversations, we have drawn a distinction between initiatives and centers focused mainly on research and those focused mainly on resources. Examples of the latter include our human cell repository, synchrotron light sources, and databases, all of which serve the biomedical community in critical ways and, in most cases, require sustained support. In contrast, many of us feel that the primary purpose of research-focused initiatives and centers is to open untapped scientific areas, providing an initial, targeted investment that enables the research to develop sufficiently so that it can be sustained through other grant mechanisms, such as R01s and P01s.

Our discussions have led to the question of whether, when and how research initiatives and centers should be ended. Should all new research initiatives and centers have hard “sunset clauses” built into them, for example at 10 years, similar to what is done for projects funded by the NIH Common Fund? Or should it be possible for them to continue indefinitely as long as they are sufficiently productive?

An additional consideration is that many of our currently funded initiatives and centers were developed during the period in which the NIH budget was doubling (see figure). With a large infusion of new investment into biomedical research, it made sense to use a significant portion of the funds to open up new scientific territory through large-scale exploration in ways that were not previously possible.

Center Funding as a Proportion of the NIGMS Budget
Fiscal Years 1998-2012
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Growth of NIGMS funding for centers (blue bars, left axis) for Fiscal Years 1998-2012. The total NIGMS budget each year during the same period is also shown (red line, right axis). The numbers on top of each blue bar represent the percentage of the total NIGMS budget committed to centers in that year. The data for 2012 do not include the funds for the Institutional Development Award (IDeA) program or the Biomedical Technology Research Centers program, which were transferred to NIGMS from the former National Center for Research Resources in that fiscal year.

In the current budget environment, in order to start a new program or bolster support for existing priorities such as investigator-initiated research, other programs must be adjusted or ended.

These issues will be central as we begin a strategic planning process to ensure that we are using the most effective and efficient mechanisms to invest the taxpayers’ money in fundamental biomedical and behavioral research. We have already begun carefully examining our existing portfolio of research initiatives and centers and considering how to balance continued support for them with other priorities and opportunities.

At last week’s National Advisory General Medical Sciences Council meeting, Council members and staff discussed the future of one existing large-scale program, the Protein Structure Initiative (PSI). The Council heard the results of a midpoint evaluation of the PSI’s third 5-year phase, PSI:Biology. The evaluators found that PSI investigators have determined an impressive number of high-quality protein structures and that some of the program’s accomplishments, including methodological ones, could not have been readily achieved through R01-type investigator-initiated grants.

The evaluators concluded that the PSI will reach a point that no longer justifies set-aside funding and, as a result, strongly recommended that NIGMS begin planning the sunset of the PSI, being careful to identify resources developed by the initiative that should be retained for use by the biomedical community.

After numerous internal discussions and consultation with the Council, we have decided to follow this advice and begin planning to sunset the PSI in its current format after the completion of PSI:Biology in 2015. We are setting up two transition-planning committees, one made up of NIGMS staff and representatives from several other parts of NIH, and a second made up of scientists from the research community. These committees will work together to recommend the best methods for phasing out the program and identifying critical resources that should be retained. The committees will also suggest emerging challenges and opportunities in structural biology that may require new, smaller-scale targeted support.

The committees and NIGMS will need a great deal of input from the biomedical community as this transition-planning process moves forward. I hope that you will freely share your thoughts and suggestions with us, now and in the future.