Following a 1 percent drop in the budget approved by Congress for NIH in fiscal year 2011, further cuts for 2012 are under consideration because of concerns over the deficit. To find out how research is being affected, Neurology Today arranged an exclusive roundtable interview with three of the institute directors whose research directly affects neurology and neuroscience: Story C. Landis, PhD, director of the NINDS; Thomas R. Insel, MD, director of the National Institute of Mental Health (NIMH); and Richard J. Hodes, MD, director of the National Institute on Aging (NIA). They spoke with Neurology Today by telephone conference call in late May.
HOW ARE BUDGETARY ISSUES AFFECTING THE NEUROSCIENCE RESEARCH AT YOUR INSTITUTE?
Dr. Landis: This year we did not receive a final budget for fiscal year 2011 until April 15. This made planning quite difficult. The fiscal year started Oct. 1, so we were halfway through before we actually knew what our budget would be. When we started the fiscal year we were optimistic we would receive the President's proposed budget, which included a small but substantial increase for NIH. By the time the budget was approved by Congress, NIH ended up receiving a 1 percent decrease. For 2012, no one thinks we'll have a budget before the beginning of the next fiscal year. The best guess is that it will be like this year, with a number of continuing resolutions.
Dr. Hodes: You have to consider the current budgets in context, Since 2003, the collective effect of annual sub‐inflationary budget increases has, by our calculations, resulted in a net 18 percent decrease in funding. We've already made all the easy cuts. Now we're turning down highly rated proposals from qualified investigators. Fantastic opportunities have been created in basic and applied neuroscience just when we are less able to afford them. The success rate of investigators' proposals that get funded by NIA is now down to something like half the success rate of 2003.
DR. THOMAS R. INSEL ...Image Tools
Dr. Insel: For us at NIMH, 2011 has been particularly difficult. We'll be funding 20 percent fewer new grants than last year, even after taking some money out of intramural funding. These are tough times.
Dr. Landis: At NINDS, your proposal now has to be ranked in the 14th percentile to get funded. That's one out of seven. This is compounded by the fact that the very significant funds that NIH received as a result of the American Recovery and Reinvestment Act have for the most part been expended.
Dr. Hodes: At NIA, for less expensive proposals — those costing under $500,000 — we can fund through the 11th percentile. For more expensive proposals, we are funding through the 8th percentile. All our institutes allow a special premium, however, for early‐stage investigators who are within a few years of completing their final training. At NIA, where the 11th percentile is the cutoff for established investigators, it is the 16th percentile for early‐stage investigators.
Dr. Landis: NINDS works very hard to manage its research portfolio so that we can fund as high as the 14th percentile. It's also important to note that early‐stage researchers receive special consideration for R01 grants at NINDS. Despite the current funding climate, we have been able to initiate important new projects. An R25 Research Education Grant allows neurology residents to take six to nine months of their residency to engage in research and funds a year of research after training to enable them to collect preliminary data for career development awards. Unfortunately, we recently had some excellent proposals to establish animal models for a number of diseases in our portfolio, i.e., Parkinson's, epilepsy, stroke, that we could not fund. There were proposals for genetic studies that looked quite promising that we could not fund. For instance, a number of genes are known to be associated with Parkinson's, but we don't know all of them yet. It would be really wonderful to be able to do whole‐genome sequencing of families. The families exist, the technologies exist, but we just don't have the funds to support it.
HOW ARE YOU MAKING THE CASE FOR THE ECONOMIC BENEFITS OF THE RESEARCH YOUR INSTITUTE FUNDS?
Dr. Landis: Many of the recent therapies for neurologic disorders (stroke, multiple sclerosis, epilepsy, enzyme replacement, etc.) grew out of NINDS‐supported research. For example, early on, NINDS funded research into the use of neural prostheses. Out of that came a number of companies and applications that make deep brain stimulators for Parkinson's, essential tremor, OCD and depression. A recent report showed that a spinal cord stimulator was a benefit in combination with intensive physical therapy for paralysis. That's also expanded into applications of permanently implanted electrodes in patients who are paralyzed, who are now moving cursors around on computer screens or using internet‐assisted devices. So whole new industries are being created out of research supported by NINDS.
Dr. Insel: One of the most important impacts of NIMH research has been on comparing the benefits of expensive new medications against older, less expensive ones. Comparative effectiveness trials supported by NIMH have involved some 10,000 patients at 200 sites. Along with other studies in the VA and the UK, for instance, we have now shown that the atypical antipsychotics are no more effective than the traditional antipsychotics that cost 10 percent as much. But beyond comparative effectiveness trials, NIMH has been studying the economic impact of mental illness and the economic benefits of treatment. Mental disorders are a leading source of disability in the US. Treatments for depression, anxiety, and psychosis can get people back to work.
DR. RICHARD J. HODES...Image Tools
Dr. Landis: NINDS has also supported comparative effectiveness studies. We just finished a trial about a year ago to compare three different anti‐epileptics for treating the most prevalent kind of childhood absence epilepsy. The study came up with clear recommendations on which is best. We're also supporting a trial comparing two treatments for multiple sclerosis, separately or in combination. Recently we supported research studies comparing medical treatment vs. stenting for intracranial stenosis. Careful analyses demonstrate that NINDS research has a major impact on clinical care and our research is cost‐effective.
Dr. Hodes: In the older population, the safety of drivers has been a major issue. Basic research supported by NIA has shown that risk factors for accidents in older drivers do not involve visual acuity per se, but that it's really about cognitive function and the ability to identify and respond to events on the periphery of vision. Scores on computer tests have been highly predictive of the risk of accidents. Interventions have also been identified that can improve performance on cognitive tests, affect executive functioning and the speed of mental processing, and even reduce traffic accidents. At least three states now use these computerized tests, and some are using the training to improve driving.
PLAYING DEVIL'S ADVOCATE HERE: WHILE STRIDES HAVE BEEN MADE IN PREVENTING AND TREATING STROKES IN RECENT YEARS, ONE WOULD BE HARD PUT TO SAY THAT MAJOR CLINICAL GAINS HAVE BEEN MADE IN PREVENTING AND TREATING SOME OF THE MOST WIDESPREAD DISORDERS THAT YOUR INSTITUTES FOCUS ON, SUCH AS AUTISM, ALZHEIMER DISEASE, SCHIZOPHRENIA, AND MAJOR DEPRESSIVE DISORDER. ARE TREATMENT BREAKTHROUGHS JUST HARDER TO COME BY IN THE BRAIN?
Dr. Insel: Your premise that we haven't had major breakthroughs in the psychiatric disorders is fair enough. There are some pretty interesting developments, however, that I would call maybe short of breakthroughs but are certainly worthy of real excitement. First, in the treatment of depression, all our antidepressants currently take three to six weeks to work. Recently, however, NIMH has funded studies showing that infusing certain drugs can have effects within hours. Second, the field has begun to recognize that the cognitive manifestations of certain psychiatric disorders often come years after biological changes in the brain have been developing. In medicine we generally don't do well treating late‐stage diseases. So we're trying to redefine schizophrenia, for instance, as a neurodevelopmental disorder, to identify changes in the brain long before you see changes in behavior. Finally, the idea has lately emerged that classic neurodevelopmental disorders, like Fragile X, Rett Syndrome and tuberous sclerosis, can be treated medically. Wouldn't that be transformative if all of a sudden these disorders become treatable, not only in infancy but potentially in adulthood?
Dr. Hodes: I would amplify one of the things Tom spoke of. Certainly in neurodegenerative diseases, particularly in Alzheimer's, we have supported a focus on the identification of neuroimaging changes or changes in cerebrospinal fluid associated with an increased risk of developing clinical signs and symptoms. The promise is that this might allow detection of the disease process at a stage when further damage can be prevented, and to address what has been a frustrating discrepancy between epidemiologic observations and the outcomes of clinical trials. The use of non‐steroidal anti‐inflammatories, for instance, was associated in epidemiologic studies with a 50 percent reduction in the risk of developing Alzheimer's disease, but when clinical trials tested their use in the early stages of the disease, no positive effect was seen. The possibility of understanding earlier signs of disease, and then monitoring those biomarkers in clinical trials to prevent development of clinical manifestations is one of the most promising ways we know to translate interventions.
Dr. Landis: I would add that besides stroke, the effective treatment of epilepsy, Parkinson's disease, and multiple sclerosis among others have also undergone substantial improvement due to modern research. Undoubtedly more progress is needed in these and many other neurological disorders. Psychiatric and some neurologic disorders are now believed to be disorders of connectivity. It is much more difficult to treat a disorder of brain connections than to treat a disease which is caused by a loss of a particular kind of neuron, or by chronic high blood pressure. It just might be that our basic understanding of the scientific underpinning of some of these diseases is not yet far enough. Yet effective treatment for many disorders now seems within reach. That's why we remain so optimistic and committed to making the most of the research funds we have.
DR. STORY C. LANDIS ...Image Tools
Diaz Granados N, Ibrahim LA, Brutsche NE, et al. Rapid resolution of suicidal ideation after a single infusion of an N‐methyl‐D‐aspartate antagonist in patients with treatment‐resistant major depressive disorder. J Clin ‐Psychiatr 2010;71(12):1605‐1611.