Apples for Health- Multiple Sclerosis: Finding Funding

Multiple Sclerosis: Finding Funding

    The search for a cure -- be it for multiple sclerosis or some other health decimator -- typically begins with the quest for funding, an undertaking that requires abilities apart from those practiced in the laboratory.

   To succeed, scientists often must morph into salesmen -- or saleswomen -- pitching proposals, proclaiming their value and compromising on price to cinch the deal. The task takes time, talent and a temperament adept at persevering through a process that, in some cases, can be fraught with pitfalls and politics, those who have traveled the road to funding attest.

   "You have to work all day to protect lives, ease suffering and conduct proper research and then worry how you will get paid and how your work will be funded and whether it will be funded," remarked neurologist Dr. Claude Genain, of the University of California, San Francisco, who has spent a decade seeking ways to restrain, retard or reverse multiple sclerosis, a devastating disease of the central nervous system.

   "I spent over half the time writing grants and trying to get funding, which involves not just correctly constructing the proposal, but then having to sell it," recalled Genain, who submitted his first grant application to the National Institutes of Health in 1996.

In 2003, he was awarded $950,000 from the nation's largest benefactor of basic biomedical research, which finances 75 percent of all MS studies in the United States.

"I started with projects I thought were scientifically exciting and excellent, yet it took me seven years to get a fraction of my request, and that's better than the norm," expressed Genain, who has seen both sides of the process, as a recipient of federal monies and a peer reviewer assessing other applicants' funding worthiness.

"It takes an average six to 10 years to get your first big NIH grant."

Typically, researchers at academic medical centers rely on support from a variety of sources, including government centers, private contributors and corporations, to carry out their investigations.

However, an award from the 116-year-old federal agency carries the most career-enhancing weight, scientists maintain.

"The prestigious NIH grant is the gold standard," Genain explained.

   "I was told I couldn't be promoted a few years ago because I didn't have NIH funding."

   Most submissions receive fair treatment by even-handed, independent experts who judge their scientific and technical merit in the first of two levels of review, Genain assessed.

   "Some proposals are rejected for a good reason, such as making improper claims or being scientifically unsound," he opined.

   "But there are also cases of judgments that have no connection to the goal of advancing medicine or helping patients."

   The NIH has taken precautions to purge the process of such potential pitfalls, agency officials said.

   "Every effort is made to shield (the examiners) from undue influence of the bureaucratic and political forces," stressed Don Luckett of the Center for Scientific Review, which evaluates three-fourths of the NIH grant proposals.

Dissatisfied applicants may appeal the results if they perceive a conflict of interest in an evaluator or think they failed to get a fair hearing.

"This occasionally occurs, and we seriously examine the situation," Luckett told United Press International. "If we feel the complaint is justified, we will see to it that the application receives another review."

In the second phase, advisory councils of the 27 funding institutes and centers evaluate how well an entry meets NIH research goals and national health needs, as determined by Congress, the Department of Health and Human Services and the public, Luckett explained.

   These experts submit their recommendations to the institute or center director, who makes the final funding decision.

   The trick is to balance judicious spending of precious resources with fair appraisal of visionary thinking.

   "We all wish we had the clairvoyance to tell the difference all the time," said Constance Atwell, a 25-year NIH veteran who directs the Division of Extramural Research, which oversees scientific review, grants and contracts at the National Institute of Neurological
Disorders and Stroke.

The challenge has swelled with the expansion of funding requests at a time of a bursting bubble of bounty. President George W. Bush's proposal for fiscal year 2005 provides a 4.3 percent increase for NIH's research-funding components after larger increases in previous years.

An average NIH award encompasses four years so the bulk of the budget is already promised for funding the remaining period of pre-approved projects, leaving, in any given year, only 25 percent of the total for new proposals.

For example, of the almost $1.1 billion NINDS earmarked for research grants in FY 2003, $807 million was set aside for previous commitments, leaving $279 million for new ventures, Atwell explained.

At the same time, demand for federal dollars to initiate research has skyrocketed, with the number of applications submitted to CSR topping 66,000 in FY 2003, a 70 percent leap from the 38,570 turned in seven years earlier.

The center will evaluate more than 16,000 proposals in the current review cycle alone, a 35 percent increase over the same period last year.

   The number of applications specifying MS as a field of study shot up from 72 in 1997 to 122 in 2002, with two-thirds of them submitted to NINDS, Atwell said.

   Over the past five years, 50 percent to 80 percent of MS researchers passed the review test -- compared to fewer than 30 percent of grant seekers overall, Atwell said.

   "This is a bustling field with a lot of promising new ideas," she said in a telephone interview.

"The science opportunities from the human genome and all other manner of scientific payoff from previous research are providing opportunities for real progress, and it's exciting, especially in neuroscience, which centers around the very hot research target of the brain, the most mysterious of organs."

In hot pursuit of the new research opportunities, the National Multiple Sclerosis Society in FY 2003 invested nearly $33 million in more than 300 -- out of a proposed 400 -- projects, including the launch of 121 studies, spokesman Terence Keane told UPI.

Last January, the society -- which has dedicated $380 million to MS research since its founding in 1946 -- awarded the single largest appropriation in its 58-year history, earmarking up to $5.5 million per grant for developing techniques to protect and restore nerve function in patients with MS.

Despite such largesse, some fund-worthy researchers continue to go empty-handed, said Genain, who, lacking sufficient revenues, had to hold up his own work for two years until a tiny non-profit research fund, called Cure MS Now! and founded by one of his patients, finally put him over the top so he could continue with his experiments.

"Because of the huge volume of NIH submissions, 50 percent of the projects must be discarded," Genain said. "That makes an extremely novel project with a concept not well understand especially vulnerable to abandonment."

   NIH developed a risk-averse mindset of necessity during periods of belt-tightening, when available revenues could cover no more than 10 percent of submitted applications, explained Ellie Ehrenfeld, who directed CSR for the past seven years.

   "When you have a group of experts in a field sitting around a table trying to conduct peer review and only one of every 10 applications has any chance of getting funded, that group tends to get very conservative, thinking, 'We better make damn sure the one we pick works,'" Ehrenfeld said in a telephone interview.

   Some scientists believed the agency's commitment to conventionality clipped the wings of fund seekers pioneering their field.

"It became clear if you had some out-of-the-box or really paradigm-shifting, ground-breaking, high-risk but potentially high-impact ideas, they were not going to make it through NIH," Ehrenfeld said.

In reaching out to the scientific community in 2002, she and Dr. Elias Zerhouni, the NIH director, heard the same message.

"There were even instructions to young investigators from their elders not to send in those bright new ideas to the NIH, but rather to submit standard ideas, then take part of the money awarded and play with it on the side in innovative ways," Ehrenfeld recalled.

The criticism climaxed as a torrent of biomedical breakthroughs across conventional boundaries, opening frontiers begging exploration.

Concerned the agency would lose its footing on the cutting edge of scientific discovery by failing to keep up with the advances, NIH's leadership launched a radical restructuring -- called the "road-map" initiative -- it hopes will attract more unorthodox but promising proposals.

"It's extremely important to ensure our review system keeps pace with the scope and practice of science," Ehrenfeld declared.

"Some 80 percent to 85 percent of the application review that we do with the old system works beautifully, but there are some things that likely will fall through the cracks because they seem a little out-of-the-box, a higher risk that will fall short of the pay line."

Atwell expressed confidence that, among other improvements, the agency could cut in half the nine to 10 months it takes, on average, to move from submitting a good idea to getting the money to carry it out.

"As we implement our new plan, I'm very optimistic we can pick up some very exciting people and projects over the next five years that may not have stood a chance in the standard process," Ehrenfeld predicted. "There are cases that can complement, expand and broaden the NIH investment in funding biomedical research in ways that will accommodate the complexity of the current scientific landscape."