SAN DIEGO — The American Heritage Science Dictionary defines "translation" — of the genetic sort — as the process in which a strand of messenger RNA directs the assembly of a sequence of amino acids to make a protein.
But at the 74th Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS; Rosemont, Illinois), a different type of translation took center stage: the process of moving scientific research into clinical development.
During a panel titled "Benchtop to Bedside: Examining the Barriers Between the Research Laboratory and the Clinical Setting," an audience poll revealed that 52% of attendees feel scientists do only "marginally well" at using information from basic science in their pursuits of applied therapies.
While researchers at the conference touted early-stage data using gene therapy and stem cells to treat osteoarthritis and other conditions, Joshua Jacobs, MD, professor of orthopedic surgery at Rush University Medical Center (Chicago), said these biologic techniques have "a long way to go" before being widely used in patient care. He pointed to a lack of "high-level clinical research studies showing new approaches are better than existing joint replacement technology."
Translating basic research into real improvements in patient care is critical in all areas of medicine, but particularly in orthopedics, where the total cost of treating musculoskeletal injuries tops $149.4 billion annually, according to AAOS.
The panelists cited the rigors of regulatory approval as a primary hurdle that translational medicine must negotiate.
Even though there are an estimated 15,000 medical device manufacturers in the U.S., Jacobs complained that he sees "the same materials used over and over."
The panel attributed this to the vast time- and cost-savings that manufacturers can achieve by pursuing the 510(k) pathway rather than the premarket application/approval pathway, the number of 510(k) applications cleared by the agency each month dwarfing the number of PMAs approved.
Even among PMAs, supplemental approvals far outnumber originals. In 2006, for instance, the FDA approved an average of 3.6 original PMAs per month, compared to an average of 55.1 supplemental PMAs.
From the survey, audience opinion was split as to whether the regulatory pathways for devices should be shortened, with 41% agreeing or strongly agreeing that they should, 48% disagreeing or strongly disagreeing. More than half (64%) of the audience agreed or strongly agreed that the current FDA process is effective in making sure products are safe.
Another hurdle discussed by the panel was the lack of funding for translational research. Venture capitalists have increasingly shied away from early-stage research in favor of funding opportunities that provide a nearer-term exit.
But there are still some, such as Allied Minds (Boston), that provide pre-seed money to university business ventures.
Universities, research institutes and even disease-advocacy groups have also stepped in to fill the translational gap.
The University of Virginia (Charlottesville, Virginia) recently hired an entrepreneur in residence to help connect researchers with companies and venture capitalists. And last fall, Stanford University School of Medicine (Stanford, Calif.) launched a $25 million translational research center. Scripps Health (San Diego) also recently launched a translational science institute. And, seeking to make early-stage research in fields like gene therapy and stem cells a reality, the ALS Association's Translational Research Advancing Therapy for ALS (TREAT) program of the ALS Association (Calabasas Hills, California) shelled out $3 million in December to Galapagos (Mechelen, Belgium) and Stem Cell Innovations (Leiden, the Netherlands/Houston).
Then, of course, there's government.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) provided grants last fall to develop four new Centers of Research Translation (CORTs), those centers intended to bring together basic and clinical research and bridge the bench-to-bedside gap.
Jacobs also mentioned a new NIH grant mechanism known as the Clinical and Translational Science Awards (CTSA). He reported that the first round of applications were received in 2006, and most requested funding to develop centers for translational research (Medical Device Daily, Nov. 9, 2006.)
Physical centers that bring research scientists and physicians together are a critical aspect of the translational process. Panelists said another hurdle to translational efforts is the fact that physicians have very little time available to interact with basic researchers. Yet collaboration between the two is key, as physicians can provide practical input as to whether or not a good research idea can be realistically applied.
Jacobs pointed to an award known as F32, part of the Ruth L. Kirschstein National Research Service Award Program, as a step toward addressing this issue. The award goes to individual postdoctoral fellows and has been used to give orthopedic residents in training hands-on experience in how to conduct clinical trials.