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Saving children's lives through scientific research, and decreasing the burden of serious, debilitating childhood illness, are cornerstones of the vision of all great children's hospitals. Unfortunately, even as discoveries surge in the laboratory, translating them to improve the outcome of pediatric illnesses is increasingly difficult. Promising therapeutic targets, for example, are frequently identified in research labs like those at Children's Hospital Boston, but few move to the stages of clinical testing, much less to pharmacy shelves.
There are a number of reasons for this disconnect between the research and clinical worlds. First, the clinicians and basic (laboratory-based) scientists who fuel outstanding academic programs are driven by different incentives. Both types of faculty are trained to be self-reliant and are highly motivated toward personal success; frequently there may be less incentive to be collaborative.
Basic scientists strive to get support from National Institutes of Health (NIH) grants, so-called RO1s, given for research on fundamental biological processes. Advancement of their academic careers relies largely upon obtaining and retaining this type of support. NIH funding for translational and pre-clinical studies—a crucial intermediate step in bringing findings to the clinic—tends to be far more difficult for them to obtain, particularly when those studies extend basic research into humans. Nor are clinical faculty, who earn support and career advancement from direct patient care, well positioned to get such grants. With increasing pressure to see as many patients as possible, they have difficulties finding the time and support to devote to translational research, or even to clinical research.
Compounding the problem, the regulatory aspects of research involving humans have become increasingly burdensome, complex and difficult to understand and comply with. This is particularly true of early-phase pilot and feasibility trials, which may benefit society, but don't necessarily benefit the individual patients to whom the clinician and institution are most devoted. In addition, scientific peer-review favors proposals that offer preliminary data and demonstration of feasibility. Both are challenging to obtain in the clinical setting, where caring for sick patients is the primary focus.
While much research is being done in the pharmaceutical industry, these profit-driven companies have little incentive to focus on childhood illnesses, which in most instances, constitute a small drug market. Institutions like Children's, which provide a unique environment, have a responsibility to further these discoveries.
But this requires taking on a number of institutional challenges. Translational research may require specialized facilities and infrastructure to assist with regulatory compliance, generate chemical and biological materials for testing, perform toxicology testing of candidate drugs and evaluate efficacy in pediatric-specific diseases. Critically needed, but more difficult to facilitate, are real—and two-way—interactions between laboratory-based scientists and clinician-scientists. Ideally, these interactions should be multidisciplinary, incorporating the outlooks and expertise of the varied members of the health team, as well as biostatisticians, health outcomes researchers and others.
To address some of these challenges, Children's recently formed a Translational Research Program, with the primary goal of facilitating the development and rapid completion of pre-clinical studies and human trials. The program has four components: infrastructure support, multidisciplinary retreats to foster interactions across research and clinical endeavors, funding of pilot translational projects initiated by faculty and a Translational Investigator Service (TIS).
The first three components were successfully launched in the spring and summer of 2008. The TIS, launching fall 2008, will identify and support a cadre of outstanding faculty with strong scientific and clinical backgrounds, significant track records of productivity and strong leadership skills. The initiative will also include new training opportunities through the newly funded Harvard Clinical and Translational Science Center (CTSC) program. Providing TIS investigators with the financial, time, and educational resources they need to conduct meaningful translational research will advance their potential as future leaders and position Children's to compete successfully for NIH, foundation, pharmaceutical and philanthropic support. But most important, success of this initiative will speed the translation of scientific discoveries into human trials and ultimately improve health care—not just for children, but also for adults.
Children's has also taken a strong leadership role in developing legislation, now pending in Congress, to support pediatric translational research nationally. The bill, known as The National Pediatric Research Consortia Act of 2007 (S. 2773/H.R. 6089), seeks to expand NIH funding of pediatric research. It authorizes the NIH to establish up to 20 national pediatric research consortia, each involving a leading "hub" pediatric medical center and numerous collaborating "spoke" institutions. These consortia would focus on both basic and translational research. The bi-partisan legislation was introduced recently in the Senate by Senators Sherrod Brown (D-OH) and Christopher 'Kit' Bond (R-MO) and in the House by Diana DeGette (D-CO) and Peter King (R-NY). It has numerous co-sponsors in both houses of Congress, and support from all the major pediatric national advocacy groups and many children's hospitals in the United States.
These efforts, one national in scope and one very local, bring much-needed new resources to leverage society's investment in basic research. This should ultimately improve the lives of children with serious and life-threatening diseases—particularly rare conditions that haven't been the focus of pharmaceutical company efforts. Hospitals that strengthen interactions between basic research and clinical care may find themselves at the forefront of therapeutic advances for the generations to come.
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