By Scott Dance, The Baltimore Sun
1:51 PM EDT, August 16, 2013
Dr. Craig Hendrix is exploring a novel concept: whether antiviral drugs can be absorbed through certain areas of the body to prevent sexual transmission of HIV.
To test such hypotheses, Hendrix and his Johns Hopkins colleagues typically can put up healthy test subjects in hospital beds overnight, which creates a more effective experiment by allowing for more data collection and limiting outside variables. But volunteers in Hendrix's study are sleeping in a hotel between two long days of blood-drawing and CT scans because of a funding squeeze in a innovative federal grant program.
Elsewhere at Hopkins, researchers are in a holding pattern, unsure whether there will be funds for projects come fall, and young researchers hoping for small pilot grants to launch careers face long odds. The funding problem also could affect researchers at the University of Maryland, Coppin State and Morgan State, as they compete for a share of a National Institutes of Health program worth tens of millions of dollars.
The NIH program, designed to fund cooperative research and resource sharing that improves health or saves lives, funnels money to dozens of universities around the nation. Hopkins alone received $80 million over the past five years.
Recently, though, the Clinical and Translational Science Awards have come under pressure. After federal lawmakers criticized the awards for pulling money from other NIH priorities, a congressionally mandated report found the program needs more oversight to succeed.
Hopkins' record in the program also has come under scrutiny. The school sought a five-year extension in 2012 but came away with only limited stopgap funding, and must wait until next month to see what the next round brings. NIH has called for changes in the way Hopkins and other schools organize their work, according to a Hopkins official who oversees the grant.
"For very large organizations, that is difficult," said Dr. Daniel Ford, who oversees the grant as vice dean for clinical investigation at Johns Hopkins Medicine.
Pressures on the program come at a difficult time for NIH. The across-the-board federal cuts known as sequestration cut the Bethesda-based agency's budget 8 percent — about $1.5 billion.
"I have never seen a year where there is going to be such a need for advocacy around NIH funding," Ford said.
The grant program seeks to transform scientific enterprise from a model in which a scientist toils alone until a "Eureka!" moment into one that emphasizes collaboration, focused on working across disciplines to solve problems rather than individually just to identify them.
It pays for a central infrastructure of scientific resources and encourages researchers from different fields to collaborate. The infrastructure includes facilities such as the inpatient research beds as well as training opportunities and small pilot grants for young scientists.
Hopkins researchers who have used the translational grant money say it helped speed and coordinate their studies.
It paid for the shared services of a chemist and labs needed to develop synthetic molecules that could inhibit enzymes that can cause cancer or influence metabolism. Investors were drawn to the technology, which has been spun out of Hopkins to form Seattle-based startup Acylin Therapeutics.
Without access to the translational research grant's central resources, "it would have been very difficult for us to have made progress in any kind of time frame that we worked in that led us to getting the biotech company launched," said Dr. Philip A. Cole, a pharmacology researcher at Hopkins and co-founder of Acylin.
For researchers receiving pilot grants, the program helps them hurdle the challenge of receiving traditional NIH grants, which fund specific research for a defined period. The application processes for NIH grants can take two years with just a one-in-10 shot of succeeding.
To dole out the pilot grants, a panel of Hopkins administrators acts like a venture capital fund, reviewing applications for $100,000 pilot awards and looking for those that can develop some sort of product or treatment. The budget had allowed for about 10 such projects per year.
"You can't be too meek and stay in clinical research these days," said Dr. Josef Coresh, a professor of epidemiology who specializes in translational research using biostatistics. "You have to believe you're going to succeed."
Budget challenges threaten the ability to do that, researchers said.
When Hopkins sought a 5-year extension of its translational grant starting in fiscal 2012, the NIH instead offered a smaller one-year pool of money. NIH officials would not release documents detailing their review of Hopkins' performance, citing an exemption from public information laws.
But Ford said it involved a push to reorganize faculty and resources to reflect the grant's transformative mission.
"Every university is being asked to provide a better way for faculty across disciplines to work together on solving the major health problems," Ford said.
Despite reduced funding, the university maintained the research infrastructure the grant created, though it has meant hiring freezes, fewer pilot projects and uncertainty for researchers planning future studies, Ford said.
"Even senior researchers are finding it more difficult," said Gerald Stacy, administrative director of Hopkins' Institute for Clinical and Translational Research, which manages the translational grant funds and programs there. "As our budget gets smaller, more people are saying, 'Can you help me?' "
For researchers like Hendrix, it could hurt the quality of experiments. The inpatient beds he used for past studies allowed him to explore new drugs in a controlled setting, eliminating potential bias from unknown variables.
Those beds have been available since the 1980s, funded by a different NIH grant that preceded the translational program. But now that they fall under the translational grant, there could be "huge implications" if that money isn't renewed, Hendrix said.
"That will necessarily limit the kinds of studies I can do, the amount of information I can get and it reduces the quality of information I can get," he said. "I won't have the same level of confidence I would have if I truly controlled for as many variables as I would like. It's very important for us that we have these inpatient beds."
The NIH scored grant applications in June, even though the decisions aren't expected until September. Ford said Hopkins officials had received their scores and were cautiously optimistic.
For University of Maryland officials, the prospect of landing a clinical and translational research award means an opportunity to amplify continuing research. The university's grant application was filed on behalf of a consortium that includes its own health system, the University of Maryland, College Park, Coppin State University, Morgan State University and Pennsylvania-based Geisinger Health System.
"The advantage of getting the CTSA and putting it under one umbrella would allow a lot of synergies to be created," said Dr. Alan Shuldiner, who leads the consortium along with Dr. Stephen Davis, both endocrinologists and research scientists at the university. "The money is important, of course, but it really creates the glue to create synergies across our institutions."
University officials would not release their grant application, which the NIH doesn't make public unless it is approved. Its website describes the consortium as seeking not just to promote translational research but advancing interdisciplinary education and work with the community to target and reduce health care disparities.
Budget cuts at NIH likely mean that any grant awards will be less than in the past. NIH officials still are weighing how the cuts might affect specific programs, but institutions like Hopkins expect translational grants to be 8 percent to 10 percent smaller.
The cuts also surely will hit the traditional NIH grants that so many researchers rely on. The hope is that success of the clinical and translational research resources will mean all research enterprise runs at a lower cost and produces more significant results — life-saving medicines and treatments — said Dr. Christopher P. Austin, director of NIH's National Center for Advancing Translational Sciences, which oversees the translational grant program.
"One of the challenges for us is to figure out how to morph our system," Austin said.
Research has historically been more focused on diagnosing problems, but the system needs to change to effectively learn how to fix those problems, he said.
But some in Congress have questioned how well the translational grants make use of NIH dollars.
In a report released in June that Congress mandated last year, the Institute of Medicine recommended that NIH consolidate the program's leadership, do more to spur collaboration among institutions and establish clearer standards for evaluating grantees and the program as a whole. The NIH is working on the recommendations.
But research advocates acknowledged that it will take time for such a broad effort to revamp research to show results.
"You want the CTSAs to be nimble and to be transformative. Of course, that's the hope," said Ann Bonham, chief scientific officer for the Association of American Medical Colleges. "As much as we would like for that to change overnight, it can take a few years to do that."
The effort dates back seven years, to 2006 under Dr. Elias A. Zerhouni, then-director of the NIH. The research is known as "translational" science for evolving laboratory experiments into drugs and other therapies that can be tested on and ultimately prescribed to humans.
Johns Hopkins joined the effort a year later, adding about $40 million in new grant money to its pool of more than $600 million it receives from NIH annually. Now 61 institutions participate.
"It's a big idea and a big plan," Hopkins' Ford told The Baltimore Sun in 2007. "And hopefully, it won't collapse under its own weight."
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