“The best way to foster translational research and accelerate the process of treatment development,” AAAS CEO Alan I. Leshner said at a 17 September briefing on Capitol Hill, is to bring together basic and clinical researchers “in almost forced collaboration.”
A new journal from AAAS, Science Translational Medicine, will help to speed medical advances by promoting better communication among academic and corporate researchers as well as doctors, according to Leshner, executive publisher of Science.
During the briefing, organized by the Council for American Medical Innovation, Leshner defined translational medicine as “the bi-directional process of moving basic research, ultimately, into clinical application.” As scientific insights are translated into patient-care settings, he added, new information based on clinical experiences can then pose new questions for basic science.
For example, Leshner noted, today's antidepressants were discovered serendipitously when clinicians tested the medications for other purposes but observed positive responses among depressed patients. This clinical breakthrough triggered basic scientists to ask why the medications seemed to ease depression, which in turn led to the discovery of multiple neurotransmitters.
Unfortunately, the process of transferring laboratory advances into clinical practice usually is much too slow to help patients particularly in an era of limited resources, said speaker Amy Comstock Rick, CEO of the Parkinsons Action Network. The traditional approach heavily funding basic research in an effort to speed viable ideas through the drug-development pipeline, into corporate laboratories, and then into drug stores following approval by the U.S. Food & Drug Administration (FDA) is not working, she said.
“The assumption for bright ideas is that the large pharmaceutical companies at the end [of the drug-development pipeline] will reach back and purchase smaller companies that are pursuing these ideas through translational research,” Comstock Rick explained. “What were finding is that the venture capital money to invest in those small companies is drying up. Biomedical research is too risky and takes too long. Also, large pharmas are getting more and more conservative in terms of reaching back and buying these ideas.”
That appears to be just one kink in the translational medicine pipeline, according to the Council for American Medical Innovation. Clinical trials help advance medical breakthroughs into working medicines and cures, but theres a growing shortfall of U.S. patients participating in clinical trials. Because only 6% of eligible patients participate in clinical trials, 87% of trials in the United States are behind in their recruitment and enrollment.
Simultaneously, the Council says, the rate at which U.S. innovators have been able to bring new drugs from the research pipeline into the market has slowed considerably. According to a report by the U.S. Government Accountability Office, the number of new drug applications submitted to the FDA each year increased by 74% between 1993 and 1999 (from 74 applications to 129), but then generally declined after 1999. Within five years, applications to the FDA had decreased 21%.
Panelist Lesa Mitchell, vice president of the Ewing Marion Kauffman Foundation, which funds economic research related to innovation and entrepreneurship, said that developing new medical treatments should be an iterative, rather than a sequential, process. Toward that end, basic and clinical researchers need better ways to share “pre-competitive” data, she said.
Leshner agreed, noting that a networked and collaborative approach to research would help basic scientists more quickly redirect their efforts if, for example, a particular pharmaceutical target no longer seems viable. “Theres a gap not only in research, but in places to talk about the research,” Leshner said. The new journal, Science Translational Medicine, will provide the field with a “communications home” where both promising new ideas and scientific dead-ends can be reported, he added.
“It sounds very obvious once you say it,” Leshner acknowledged. Yet, basic researchers working in large federal laboratories are trained to focus in a laser-like fashion on a specific question, which is then exhaustively pursued, whereas clinical researchers must be more concerned with FDA requirements, public perceptions and market conditions. The two research communities rarely have opportunities to share information.
“In translational research,” Leshner said, “you're trying to more broadly conceptualize illness in all its facets.”
Comstock Rick discussed a five-year grant cycle as being traditional for agencies such as the National Institutes of Health (NIH). She proposed more regular “check-in” points throughout the life of each grant, to more closely track researchers progress. She said that it's also important to look for any potential disincentives to corporate participation in research. If no biomarker has been identified for a particular disease, for example, corporate funders may be less likely to support long-term research efforts to find a cure, according to Comstock Rick.
Mitchell described two new business models for speeding promising medical ideas into the marketplace.
Under one model, she reported, universities such as the Massachusetts Institute of Technology and the University of California at San Diego have established successful “proof-of-concept,” or translational research, centers. These multi-disciplinary centers bring diverse experts together and encourage partnerships with disease philanthropies as well as corporations.
Under a second approach to translational research, Mitchell said, philanthropists such as Parkinson's advocate Michael J. Fox and Bob Beale of the Cystic Fibrosis Foundation are getting more directly involved in basic science. As a first “venture philanthropy” success story, Mitchell pointed to the cancer medication Avastin, which was approved by the FDA this spring after Steve Case's foundation helped to support Genentech's intensive drug-development efforts.
The Ewing Marion Kauffman Foundation also is promoting a Translational Medical Alliance to bring together “rock-star scientists” with business leaders, Mitchell reported.
Other topics covered at the Hill briefing included strategies for realigning incentives to help promote translational advances, educational initiatives such as a post-doctoral fellows program supported by Mitchell's foundation, and a proposal described by Comstock Rick to establish a new Office of Translational Research within NIH.
Science Translational Medicine debuts 7 October. In an announcement of the new journal, Science Editor-in-Chief Bruce Alberts said that it will serve researchers and management in academia, government, and the biotechnology and pharmaceutical industries, as well as physician scientists, regulators, policy-makers, investors, business developers, and funding agencies.