Medical Writing, Editing & Grantsmanship

Update: CSR (but not the NIH) has announced Toni’s resignation. Nature has an interview with him as well.

Toni Scarpa is resigning from CSR as of September. He is the trailing spouse of Meredith Bond, who will move up from Department Chair to Dean of the College of Sciences and Health Professions at Cleveland State University. Toni of course came to the NIH from Case Western and will no doubt find something to keep him off the streets and out of the pool halls in his old stomping grounds.

Toni sent out a farewell notice to his colleagues yesterday, noting that:

My departure will permit the NIH Director to search for a new CSR leader who will have renewed enthusiasm and fresher ideas for this strategically important position, and who will also better match the Director’s vision and management style.

Yes, things have changed since the departure of the Great Zerhouni.

Toni modestly summarizes the significant accomplishments and challenges that he managed while at CSR:

These 6 years have been an exhilarating experience and I consider myself fortunate and privileged to have served in a period of unprecedented changes, and opportunities, in peer review. Thanks to a professional and dedicated staff, CSR has managed to review 50% more applications, in addition to 40,000 ARRA applications two years ago. It was also a fulfilling experience to be able to help NIH design the first major changes in peer review in 65 year and to have CSR implementing them.

And he signs off with kind recognition of his colleagues in and outside the NIH:

Personally it was an incredible privilege to meet with thousands of faculty, researchers and reviewers and to interact personally with every study section chair. Even more of a privilege was to interact with many of you as a colleague and often as a friend. I doubt there is anywhere in the world a group of people so smart, professional, dedicated and effective, and at the same time overworked, underpaid and underappreciated.

Here, here. Thanks for all you have done for the extramural community, Toni. The beer in Cleveland has no doubt improved since you left, but the winters have not. Ciao.

Update: Collins has appointed Richard Nakamura, PhD to serve as Acting Director of CSR starting September 18 (Deputy Director Cheryl Kitt, PhD will assume leadership from Sept 3-18).

Last week, NHLBI announced it would no longer participate in the R21 parent announcement. Today, it gave notice that no new nominations would be made for MERIT (R37) awards, though the 79 current MERIT awardees will not be affected. While each IC has its own selection criteria, generally MERIT awards are made based on competing renewal R01 applications by established investigators with a track record of NIH funding that score in the top few percentile. The benefit of a MERIT award is that it is extended based on the PI’s progress report rather than a full competing renewal application (IC staff recommend extension, which is then considered by Council). Although only the top 5% of NIH-funded investigators receive MERIT awards, they are the closest thing to HHMI grants, as exemplified by NIGMS’ description:

The objective of the MERIT Award is to provide long-term, stable support to investigators whose research competence and productivity are distinctly superior and who are likely to continue to perform in an outstanding manner. The provision of long-term stable support to such investigators is expected to foster their continued creativity and spare them the administrative burdens associated with preparation and submission of full-length research grant applications. This may allow investigators the opportunity to take greater risks, be more adventurous in their lines of inquiry or take the time to develop new techniques.

Given the likely budget limitations in coming years, it is not surprising that ICs might trim mechanisms from their budget, but I am sure some (especially MERIT awardees) may decry the loss of the one mechanism that frees productive PIs from the burden of grant writing (or at least some of this burden), along the model of HHMI investigators. On the other hand, an upcoming report from 3 economists, “Incentives and Creativity: Evidence from the Academic Life Sciences,” suggests MERIT awardees cannot match HHMI investigators in terms of productivity or creativity:

The researchers identified 73 life scientists given HHMI support in three years — 1993, 1994, and 1995 — and tracked their work through 2006. Because these scientists were quite well-regarded before getting HHMI funding, the study compared them to groups of similarly accomplished scientists receiving NIH grants: one group of 393 scientists who had received early-career prizes, and another group of 92 scientists receiving the NIH’s MERIT funding, awarded to highly promising projects.

Among other things, Azoulay, Manso, and Graff Zivin analyzed how often these scientists published articles that were among the top 5 percent or top 1 percent of the most cited papers in their fields. They also studied “creativity” in lab research by seeing how often the scientists began using new keywords to describe the subjects of their articles.

Their findings show that compared to the early-career prize winners with NIH grants, the HHMI-funded scientists produced twice as many papers in the top 5 percent in terms of citations, and three times as many in the top 1 percent. Compared to the NIH-funded scientists with MERIT grants, the HHMI group produced about the same quantity of papers in the top 5 percent by citation, but 50 percent more papers in the top 1 percent.

The study also found that the HHMI investigators had about 10 percent more variety in the keywords they introduced into their own work than the early-career prizewinners from the NIH, and were cited in a greater range of journals. Additionally, the HHMI-backed scientists mentored more early-career prize-winning scientists themselves (1.13 per person) compared to the NIH-funded group (0.24 per person).

The period analyzed pre-dates the recent Pioneer (DP1), Innovator (DP2), EUREKA (R01), and Transformative (R01) awards that might better match how HHMI investigators are selected (versus based on the requirement of a long-standing, currently funded productive project, as with MERIT), so perhaps NHLBI is thinking these and other innovative NIH funding mechanisms coming down the pike are the better way to spend limited dollars on investigators with the potential to do creative, transformative research. Or perhaps they are simply protecting their budget to maintain their R01 portfolio in the years to come.

Once again, the NIH Bluebrint for Neuroscience Research has issued a request for information notice “soliciting ideas from the neuroscience research community on how best to support or accelerate neuroscience research.” That is, what should we be funding.

Though, it’s not like they have a lot of funds to award:

For FY12 and FY13, it is anticipated that limited funding will be available each year (no more than $4 million) while FY14 may provide greater flexibility as several NIH Blueprint projects come to an end.

But … you might as well get your two cents in by addressing these four items:

1. Identify areas of neuroscience research that could be accelerated by the development of specific research resources or tools.
2. What are the major opportunities for, and impediments to, advancing neuroscience research?
3. What are the 2-3 highest priority tools or resources needed to capitalize on the scientific opportunities and overcome obstacles to progress in neuroscience research?
4. Describe how NIH Blueprint might best facilitate the development of these tools/resources.

Responses to the RFI will be accepted until Friday, September 9, 2011.

No doubt to counter a less than enthusiastic response from Congress, Francis Collins has published a commentary in Science Translational Medicine addressing specific concerns raised in hearings (e.g., referring to “NCATS senior leadership—to be recruited in the next year—” and “make it abundantly clear that NIH is not attempting to become a drug development company”) and reinforcing the reality (i.e., resistence is futile) of his new National Center for Advancing Translational Sciences (NCATS):

With the establishment of NCATS in the fall of 2011, NIH aims to reengineer the translation process by bringing together expertise from the public and private sectors in an atmosphere of collaboration and precompetitive transparency.

He also restates the NCATS mission on its own:

to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of diseases and conditions.

and in partnership with the FDA:

Through this assembly of scientific and regulatory expertises and technologies as well as interdisciplinary cross-pollination, NCATS will catalyze the development of new insights that, when implemented, can have broad benefits across diverse translational projects.

Not surprisingly, he uses the Human Genome Project as the historical parallel of his new paradigm-shifting initiative and the untapped opportunities from GWAS to identify new drug targets. A better parallel might have been NCCAM, in that the approach (complementary/alternative) rather than the underlying disorder/biological system is the focus. He then notes that:

Early discussions with a variety of stakeholders have identified several components of translational science that are ripe for the new scientific approach offered by NCATS and will likely be the subject of early targeted funding opportunities.

It would be nice to know who these stakeholders were and the precompetitive transparent process by which they selected the 10 programmatic priorities covered by Collins: therapeutic target validation, chemistry, virtual drug design, preclinical toxicology, biomarkers, efficacy testing, phase zero clincal trials, rescuing and repurposing, clinical trial design, and postmarketing research. Now, these areas are interesting points of focus in terms of improving the efficiency of the development process … but they are already being pursued in the absence of NCATS and could have worked as Roadmap initiatives, which would have benefited from the expertise, resources, and strategic priorities of all the ICs.

He is a little less clear, still, explaining how NCATS will work with and facilitate (versus replace) industry efforts at drug development. Early on, he lays out the threat facing private research and development:

Faced with economic stresses and patent expirations, many pharmaceutical companies are reducing their investments in research, and biotechnology companies are finding it difficult to obtain venture capital for projects that need many years of support to achieve profitability.

Collins identifies the “middle zone” of translational research (“assessment of … potential to lead to a clinical advance; development of candidate diagnostics, devices, or therapeutics; optimization of the candidates in preclinical settings; regulatory assessment of the data to determine the potential for human use”) as the bottleneck industry cannot overcome alone:

The development of systematic approaches for target validation, the reengineering of rate-limiting and failure-prone steps in the therapeutic development process, and the urgent need to increase the critical mass of well-trained individuals to drive innovations are among the various translational challenges that are ill-suited for solutions derived solely from the private sector.

So he suggests that:

The new center will instead seek to invest in the kind of science that creates powerful new tools and technologies that can be adopted widely by researchers in public and private sectors to streamline and derisk the therapeutic development process.

Why creating a new center at the cost of a well-functioning center (NCRR) was required is not addressed … in fact, NCRR is never mentioned. Collins remains confident the “whole” of NCATS will be greater than the sum of its existing parts. The one new program, if the amended NIH budget (NCATS added, NCRR subtracted) is approved by Congress, the Cure Acceleration Network (CAN), remains poorly defined. His table refers to CAN as supporting “translational solutions to high-need medical problems” with “much-needed flexible funding authorities” … and a lot more money per award (up to $15M) made to “academic and private-sector consortia, with such projects managed “actively and aggressively by using mechanisms similar to those used by DARPA.” Hmm. Hope this doesn’t mean the NIH intends to follow the DoD down the path of funding black projects as well …