Sometime this summer, researchers funded by a new center at the National Institutes of Health will begin trying to construct a new tool to test whether drugs are likely to be safe in humans. If successful, the technique could significantly shorten the time it takes for drug developers to figure out whether a product can pass the first test facing a proposed therapy — whether it will end up hurting the patients that it’s intended to help.
Now, most proposed drugs are tested first in animals and then in humans, a lengthy process that can take years while patients wait to see whether a potential cure will be safe and effective enough to win Food and Drug Administration approval and result in a useful treatment.
But under the NIH plan, scientists would get money to combine human cells with a computer chip. Federal officials hope that the tissue-on-chip tests would be not only faster than animal trials but also cheaper and more accurate.
The initiative is overseen not only by the NIH and the FDA but also by the Defense Advanced Research Projects Agency, the Pentagon arm known for funding blue-sky scientific experiments. NIH officials will provide $70 million during the next five years for the parts of the project focused on human physiology, and DARPA officials are offering the same amount to finance the engineering of structures that can support the human cells.
The project is just one of many that will be supported by a new center created at the NIH in December known as the National Center for Advancing Translational Sciences. NIH Director Francis Collins pushed for the establishment of the center out of frustration at the long delays in transforming scientific findings from gee-whiz discoveries into practical drugs, diagnostic tests or vaccines. Collins said the majority of the NIH’s overall $30 billion-plus budget will continue to go toward funding basic science but that the new $575 million center will help coordinate and focus efforts to help push research from the lab to the hospital or doctor’s office. NCATS will stretch its dollars by collaborating with other agencies and with private companies or academic institutions with the aim of spurring innovation.
Not everyone is convinced that a new institute is needed. At hearings in the House and Senate in March, some lawmakers worried that the initiative will take on tasks usually done by drug or biotech companies. Others complained about proposed cuts to other NIH efforts and worried that the new program would drain resources from well-established institutes.
A big part of Collins’ job over the next year, as NCATS begins its work as one of 27 full institutes and centers at the agency, is to persuade appropriators and other lawmakers not to undermine the new program. Lawmakers have made it clear that they will be watching.
At a House Appropriations subcommittee last month, several Members raised concerns. “Congress did not provide or envision NCATS or NIH to have authority to compete with industry or become a drug-developing organization,” said Rep. Denny Rehberg, the Montana Republican who chairs the panel that writes the first draft of the annual NIH budget. He repeated the statement for emphasis.
Because it is new and so much is unknown about the types of work that NCATS might take on, some lawmakers argue that the new institute’s funding could be better used elsewhere. “Why would you want to spend time and dollars duplicating what the private sector might do with its own patents rather than exploring areas where there’s been almost no research into a disease solution?” Rep. Cynthia Lummis (R-Wyo.) asked at the same hearing.
A similar criticism was lodged by former Merck CEO Roy Vagelos, who said at the hearing that he “probably would not have started NCATS” because it doesn’t have the expertise or funding necessary to have a big effect on drug development. He said the NIH should focus on basic science, which makes up about 54 percent of its current budget. “If anyone in this total audience believes that there is something that NCATS is going to do that the industry thinks is critical and that they are not doing — I think that is incredible to think that,” Vagelos said. “If you believe that, then you believe in fairies.”
NIH officials said they are taking care to avoid projects that could be done by others. Collins said the NIH will stop short of product development but will work with companies to fill in research gaps that have kept new information from being turned into useful treatments. The point is to develop what the center’s acting deputy director, Kathy Hudson, called “cool new tools and methods” that could often be used in a broad way to improve research for all drugs, not one particular product.
NIH officials have only announced a few initiatives that NCATS is expected to fund. One is the cell-on-a-chip project with DARPA.
Another project is designed to find new uses for existing drugs, some of which have already been approved for sale in the United States by the FDA. The center is creating a database of approved and investigational drugs and, with FDA guidance, is looking for drugs that could be tested to see whether they would work to treat other diseases.
A third big NCATS initiative is developing new tools to understand how proteins or cellular structures are associated with specific diseases. Scientists have learned a great deal about the potential causes of disease since Collins and other scientists finished the project to map the human genome in 2003. But using that knowledge in drug development has remained difficult.
Collins wants to improve the part of the drug development process that uses methods to ensure that a certain cellular protein, RNA or DNA really participates in causing a disease. Once the detailed structure of the protein (or “target,” as scientists call it) is identified, researchers can test whether a drug affects the structure in a way that would stop the disease. (For example, a drug might inhibit the action of an enzyme that is tied to a disease.) NIH officials say the current ways of validating the role of targets such as proteins in disease are not as accurate as they could be, so NCATS officials plan to fund research to improve the methods.
The goal behind all of the center’s plans is to speed up the development of cures. “Bottlenecks continue to vex this process, resulting in long [drug] development time, very high failure rates and steep costs,” Collins said. “We need to re-engineer this pipeline.”
Hudson said the center is needed to bring together programs, many of which already existed at the NIH, that can result in better drugs or other products that can prolong or improve patients’ lives.
“All of us have had the experience that either ourselves or a family member has a particular disease or disorder, and you hear far too often from health care providers that there’s nothing more to be done,” Hudson said. “When you look at how many inefficiencies there are along the way, it cried out for some re-engineering” of the drug development process and the NIH’s efforts to support it.
Robbing Peter to Pay Paul
Some lawmakers are concerned about the amount of funding that will go to NCATS while other programs face cuts.
The center’s acting director, Thomas Insel, told lawmakers that the vast majority of the programs at NCATS already existed in some form at the NIH. The center is just a way of bringing all of the translation science projects together under one roof, he said.
The exception is the $10 million Cures Acceleration Network aimed at finding cures for rare diseases. The administration wants its budget to grow fivefold in the coming fiscal year.
More than 80 percent of the budget for NCATS comes from the Clinical and Translational Science Awards, created in 2006. About 60 centers around the nation are funded through the awards. CTSA funding, as it is currently configured, goes to such initiatives as research on new chemical processes to improve imaging scans, the technique of lowering injured patients’ body temperature to reduce harm, identifying genes linked to dementia and a variety of studies comparing different kinds of treatments for the same medical condition.
At the House and Senate hearings, several lawmakers expressed concerns about cuts to other NIH programs, suspecting that money from those cuts is going to NCATS. One program is the Institutional Development Award program, which is intended to spread research and scientific capacity in regions that historically have not received a lot of NIH funding. “Any time you start something new, people wonder where you’re going to get it, particularly in these budget times,” said Rep. Mike Simpson (R-Idaho), another member of the House Appropriations subcommittee that oversees the agency. “They’re worried that it’s going to come out of what they have been doing in the past.”
Collins said lawmakers should not make a direct connection between cuts to the IDA program and funding for NCATS. “Those are not the same dollars that just got moved from one box to the other,” he said. “This is part of a big overall plan to try to figure out where the scientific opportunities are most pressing.”
Clearly, Collins believes that the most pressing opportunities are in the work at NCATS. As for the concerns raised by lawmakers, Hudson said, “Frankly, the only way to put those misperceptions to rest is through actions.”