Sequestration and Hemophilia Research

A Q&A with NIH’s W. Keith Hoots, MD
Author: Emily Wojcik

This year’s mandatory federal budget cuts, known as “the sequester,” have been raising concerns about the future of biomedical research, particularly rarer disorders like hemophilia. The National Institutes of Health (NIH) faces across-the-board cuts in 2013 of $1.71 billion.

To find out how these cuts will affect future research, HemAware spoke with W. Keith Hoots, MD, director of the Division of Blood Diseases and Resources at the NIH’s National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, MD. He is also the former president of the Hemophilia Research Society of North America and former medical director of the Gulf States Hemophilia and Thrombosis Treatment Center in Houston. 

HemAware: Can you give an overview of the NHLBI’s role in biomedical research and the overall impact of the sequester?

Hoots: The NHLBI is the third-largest institute in NIH. It is charged with funding the biological research that has an impact on cardiac, lung and blood health. Cardiovascular disease represents the largest community in terms of its prevalence, morbidity (diseases associated with it) and mortality in this country and around the world.

The sequestration is affecting everything significantly. The NIH budget has been flat, in real dollars, for the last several years, and declining in inflationary-adjusted dollars. Our buying power has dropped. To then superimpose a 5.8% across-the-board cut means the cuts get amplified. We are making very difficult decisions these days that we have never had to make before.

HemAware: What does that mean for research funding, especially for rarer bleeding disorders?

Hoots: There are definitely challenges. For instance, to determine whether a new drug is effective, trials have to be designed with numbers of participants that will give statistical indicators as to whether the drug is superior to a standard of care. When dealing with rare disorders like hemophilia, enrolling a large enough number of research subjects to do clinical trials is a challenge.

However, compared to some diseases, hemophilia has one notable advantage: There are effective therapies for hemophilia A and B. There are also potential new therapies that have already been investigated in humans, such as gene transfer for hemophilia B, which are showing some potential for success. A number of drugs are in development. Because they are expensive therapies, there are incentives for pharmaceutical companies to develop them, get them licensed by the Food and Drug Administration (FDA), and get them marketed and sold.

Many of the clinical trials of therapies for patients with hemophilia are sponsored by pharmaceutical companies. That’s why we have recombinant factor and why we are developing longer-acting recombinant factor. For us, the challenge across all blood diseases is to enhance the development of potential therapies and to get them to the point where there is a reason for pharmaceutical companies to develop them.

HemAware: Does this private funding help lessen the impact of the sequestration for research into bleeding disorders, in terms of easing pressure on the NIH?

Hoots: I would say yes in the near to intermediate term, over the next two to eight years. It is a better position to be in because the drugs are already in clinical trials for hemophilia. It takes several years for drugs to go from animal testing to clinical trials in people, to licensing and marketing. To prove an idea first in the lab, then in animals, then humans, in steps that start with safety and move towards efficacy—increases the timeline by 10 years, on average.

HemAware: NHLBI Director Gary H. Gibbons, MD, wrote in May 2013 that, going forward, funding will need to emphasize research project (R01) grants. What does that mean?

Hoots: There are two major categories for research that we fund. The largest and, I think, most important is R01, or investigator-initiated projects that bubble up from the scientists themselves. We have thousands of scientists in the United States who come up with great ideas, and somebody has to fund them. R01s have been the mainstay of NIH funding since its inception in the 1940s and constitute about 70% of everything we fund. The other 30% of NHF funding is for “initiatives,” areas in which there isn’t much scientific activity, so we request that scientists apply to do research there.

Currently, we’re reducing the funding for initiatives, to avoid impairing the ideas that bubble up. Our rationale is that it’s better to have more minds thinking about what needs to be done than fewer minds. But our flexibility in identifying underserved areas is reduced for targeted funding in other areas.

HemAware: Where do you see NHLBI going in terms of new research, in light of the sequestration now and in the future?

Hoots: There are  encouraging developments in hemophilia right now. When I was a hemophilia treater, we hoped that the days of gene transfer would arrive earlier. The fact that there’s been a successful trial for gene therapy treatment for hemophilia B is very encouraging. Things are headed in the right direction.

Looking ahead, we’re very interested in regenerative medicine. I think it will be very important for the adverse effects of diseases like hemophilia that create chronic debilitating outcomes. We may soon be able to identify and either reverse or prevent serious problems with new drugs and new therapies. I think hemophilia is sitting in a reasonable position to benefit.

The rate at which progress comes will be influenced by everything, including budget. As long as we apply the resources the American people provide us in the best way possible, we will have done our job. I am very confident that progress is coming.

Learn More:

Read “Genotyping for Progress,” HemAware.

Read “The Benefits of Knowing Your Genotype,” HemAware.