ARTICLE IN BRIEF
The article discusses the impact that sequester-associated cuts in federal funding are having on the long-running Framingham Heart Study.
“The town that changed America's hearts” is printed on signposts throughout the town of Framingham, MA, in honor of the town's 65-year commitment to the longest running cardiovascular epidemiological study in the world, the Framingham Heart Study (FHS). More than 15,000 people — spanning three generations of Framingham residents and their children — have participated in FHS since its inception in 1948. Findings from the study have helped identify major risk factors for stroke and cardiovascular disease, including high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity — as well as valuable information on the effects of related factors such as blood triglyceride and HDL cholesterol levels, age, gender, and psychosocial issues.
But, the principal investigator of the long-running study told Neurology Today, the FHS has been hit with a devastating 40-percent reduction in funding as a direct result of sequestration and an alteration in the approach toward “big data.” Instead of receiving $9 million dollars in the sixth year of Framingham's seven-year contract, the primary federal agency funding the initiative — the National Heart, Lung, and Blood Institute (NHLBI) — notified the FHS that they would only receive $5 million for the year. [THE NHLBI, like all the NIH institutes, has faced 5 percent across-the-board budget cuts as a result of the sequester, a consequence spelled out by the Budget Control Act of 2011 if a Congressional committee failed to produce legislation that would reduce the federal budget deficit by $1.2 trillion over ten years.]
“So, between last May and [for the period extended through] March 31, 2014, we [have] had to lay off 19 people out of a team of about 75 because we didn't have the support for their salaries,” said Philip Wolf, MD, principal investigator of the Framingham Heart Study and professor of neurology at Boston University School of Medicine. This was a very difficult blow; many of these individuals had been with us for many years, he added.
Dr. Wolf told Neurology Today that he is most afraid of losing the “personal element” that they have established with their Framingham participants. The retention rate among the offspring of study participants is 85 percent, he said, because “participants have a great deal of pride, community spirit, and allegiance to the study. We're concerned we'll lose this continuity if we have no exams and no contact with the participants.” The third generation of study participants is now in midlife, approximately 45 years old, he said, which would be an ideal opportunity to intercede and try to prevent diseases like stroke and Alzheimer's disease from developing. “We think it is unfortunate timing for a third generation, which would be due for an exam in about a year.”
Right now, the indication is that FHS will be able to continue to track mortality, events (stroke, heart attack, cancer), and conduct questionnaires, but there will be no new imaging or exams, Dr. Wolf said. “What we're interested in and what could be affected [by the reduced funding] is not just whether someone has a clinical stroke or dies from a stroke, but rather the subclinical conditions — we've been doing MRI and cognitive function testing on these people periodically to map their structural changes and cognitive decline, which isn't something that's nearly as well done by telephone or by questionnaire,” he explained.
One of the best ways to detect future stroke and dementia is to capture disease at an early stage, before people show up with symptoms, by looking at MRI scans for evidence of silent stroke or white matter disease, Mitchell S.V. Elkind, MD, a principal investigator of the Northern Manhattan Stroke Study, another longitudinal community-based study, said. “If we are unable to determine the presence of those conditions and how they are associated with risk factors, then we will never know about these preclinical conditions. It is now more important than ever to understand those processes better.”
To reduce research costs, more and more investigators are turning to phone and Internet surveys and questionnaires. However, Dr. Wolf does not believe that this will yield the same quality of information. “We rent a wing of a building in Framingham that serves as the focus for our scientific work. Any particular year, we also train six or eight Fellows — usually cardiologists, but also neurologists and statisticians — who have then gone on to be productive and important investigators in cardiovascular disease, neurology, stroke, and dementia.”
For many years, we have been very fortunate to be supported by the NHLBI, as well as NIA and National Institute of Neurological Disorders and Stroke (NINDS), he continued, but “we understand that their payline is very low and that they aim to fund more investigator-initiated research grants accordingly by cutting back the amount of money they're giving to contracts, particularly prospective epidemiologic studies.”
We don't know what next year holds, said Dr. Wolf. “It's unfortunate because it really does impinge on our ability to do science,” he said. “We're pursuing a number of strategies to replace this loss of funding and hope to carry on as we did after a similar funding cut-off in 1968.”
REDUCING RESEARCH COSTS, BUT AT WHAT PRICE?
“Our purchasing power [at the National Institutes of Health] is down to where it was in 2000; it's not good,” said Walter Koroshetz, MD, deputy director of the National Institutes of Neurological Diseases and Stroke (NINDS). “As a result, NINDS is struggling to get needed resources to our investigators. NINDS is committed to preserving as stable a funding environment as possible for the majority of our investigator-initiated research. However the large multicenter projects, which are most expensive are really under the microscope. That includes some of the big epidemiologic studies, centers grants, program project grants, and clinical trials. ... To advance the science, we all realize that you need a portfolio of different projects, including the big epidemiologic projects, clinical trials to test new therapies, research infrastructure, etc., which may carry a lot of upfront costs.”
Dr. Elkind acknowledged that many epidemiologic studies “involve recruiting large numbers of people and following them over time, which means lots of research assistants, making telephone calls and interviewing people, and a lot of tests like ultrasounds, MRI scans, neuropsychological evaluations — all fairly labor-intensive, technology-intensive tests, which can be costly. So the Institutes have to decide: Are they going to fund a few of these large studies or are they going to fund a lot of smaller studies? I think they haven't yet figured out the optimal way to go about this.”
Regarding his own project, Dr. Elkind, an associate professor of neurology and epidemiology and the fellowships director in the neurology department at Columbia University School of Medicine, said that the Northern Manhattan Study was fortunate to only receive a 4-5 percent funding cut due to sequestration. However, Dr. Elkind and colleagues are already planning strategies for keeping their research afloat in spite of continued budget cuts.
“We would like to think that we'll be successful by leveraging our experience doing large epidemiologic studies into conducting more interventional research that has a more direct outcome in terms of patient care,” he said. “We think we're in a good position to do these kinds of studies, but we also know that if we do intervene in our cohort, we lose the ability to conduct the observational study in a natural setting that has been the strength of our research in the past.”
Ultimately, Dr. Elkind said, “we recognize that there are fiscal constraints federally and there may be a political climate that is less conducive to research, so we have to focus in on those questions that we think are the most important, make a strong case for why the funding is needed, and probably emphasize things that we think have the highest likelihood of being successful interventions.
“The plus-side is that it will cost less money, but the downside is that we may not make as many discoveries as perhaps we did in the past, and we may miss things that could be important,” said Dr. Elkind.
DR. WALTER KOROSHETZ: ‘ON SURVIVING SEQUESTRATION’
In his oral testimony on May 15 to the Senate Appropriation Committee for fiscal year 2014, National Institutes of Health Director Francis S. Collins, MD, PhD, said, “Many of my role models, top scientists with amazing ideas and the potential to change the world, are unable to get funding. I can't erase the fear that this is my future.... Sequestration is compromising the future of medical research and slowing improvement in the health of all Americans.”
In order to survive sequestration, Walter Koroshetz, MD, deputy director of the National Institute of Neurological Disorders and Stroke, told Neurology Today, researchers should try to address this question: “How can we get the answers that we want for less cost?”
“We've been trying hard to encourage more cost-effective research, by eliminating inefficiencies in the system, for example, by creating effective clinical trial networks. In the old system, a clinical trial would get funded, the government would spend a lot of money starting it up, do its work, and would spend more money as it closed down. And then you'd repeat the process for another study and there would be a lot of redundant costs.” By creating a clinical trial network, such as the NINDS Stroke Trials Network and NeuroNEXT, the start-up and the close-down costs are taken away, he explained.
“Another question neurology researchers have to ask, he added, is whether we can employ new technology to cut costs. Do we really need study participants to come in for all the follow-up visits? Or can we do follow-ups using Skype? Would that be more efficient? Easier for the patient? Cost less?” Other technologies, such as electronic medical records, said Dr. Koroshetz, are also touted as presenting an opportunity for gathering more cost-efficient answers since the data are already being collected in the practice setting.
“It wasn't so expensive to do research when I first started my career in the 1970s and 80s, but it wasn't as complicated; in those days, the practitioners were researchers. In these days, there are researchers and then there are practitioners, but it's harder to have research in practice. Would it be more cost-effective to start getting data out of practice, and would that have lots of other benefits by involving more patients and doctors in research?” he asked.
While the focus in medical research is shifting to cost-effective care, the government is also shining some light on the importance of patient-reported outcomes. In many studies, Dr. Koroshetz explained, the outcome measures are neurologic scales or extensions of the neurologic exam that the neurologist performs, “but what we really care about is how the patient is doing.” With the use of the Internet, he said, there are groups like 23andMe that are using patient-reported responses as a statistically valid research tool, for example, in the study of lithium use in people with amyotrophic lateral sclerosis. “We did a study that cost us a couple of million dollars, and this Internet-based study got the same answer, but it cost hardly anything,” Dr. Koroshetz told Neurology Today. “The Patient-Centered Outcomes Research Institute funds these very patient-oriented research questions.”
The cost-reduction strategies are a bit more tenuous when it comes to imaging tools in neurology research, Dr. Koroshetz acknowledged; “we're so dependent on imaging because it is our window into what is going on in the brain or spinal cord; it's a great tool but it's a big problem in terms of cost.” NIH is working with GE right now to build a head-only MR scanner that would be much less expensive, he said.
Nevertheless, we must remember that the US investment in neuroscience research is still large, Dr. Koroshetz said, and “although financial concerns certainly impact the budget, working with the neurology community we're going to advance the science in spite of more difficult financial times. Neurology is not going to stop improving the health of our patients. We still need young people to come in with their fresh ideas, and there are lots of opportunities in neurology for young people to make great discoveries.
“We've been used to budgets increasing all the time and that's not going to happen... we can't give up. We just have to get more clever.”