Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 9
Page 9 BUILDING AND SUPPORTING THE RESEARCH ENTERPRISE In plenary presentation, Dr. Stephen Hauser drew attention to the importance of a “functional superstructure” to support MS research in a highly dynamic and changing scientific and clinical environment. He referred to MS as a “prototypic multidisciplinary disease” that transcends individual disciplines and specialties. Although neurologists have traditionally viewed MS as an immunological disease, Dr. Hauser noted that in light of renewed awareness about neural degeneration and remyelination, “This all might change.” He urged participants to view the workshop as “an opportunity for us to really re-think, in a somewhat more radical way, how we might bring a new model to this clinical problem.” The breakout group focused its discussion on the following topics: recruitment of young researchers, centers and program projects, clinical trials network, and protection against false leads. The breakout group refrained from prioritizing their recommendations (14–16 and 18), because according to Christine Purdy, the group's rapporteur, the group agreed that with one exception the recommendations were equally important. The single exception was the recommendation (#18) for an organizational structure to protect against investing research resources on false leads for MS pathogens and disease markers. Most members of the breakout group did not accept this recommendation. Recruitment of Younger Researchers The breakout group pointed out that fellowships are readily available for recruitment of young researchers (recommendation #14). The real problem in their view is lack of sufficient motivation to pursue clinical research in general and MS research in particular. The group underscored the importance of encouraging young researchers, as early in their careers as possible, by providing visible role models and mentors, career excitement and challenge, long-term security, and scientific opportunity. The breakout group suggested the following steps to stimulate young investigators to enter the field: Hold a series of workshops around particular topics to attract young investigators from different disciplines, including medical students, pre-doctoral students, postdoctoral candidates, and neurology residents; Provide medical students with summer fellowships or year-long fellowships in MS research; Bring into the MS field recent graduates, as well as established scientists, in related disciplines, for example, genomics, bioinformatics; Offer MS weekend retreats to accompany Keystone symposia and satellite symposia for the annual Society for Neuroscience meeting; Offer research grants in partnership with bioengineering researchers;
OCR for page 10
Page 10 Offer more fellowships in conjunction with MS funding proposals; Create partnerships between industry and government to support MS centers patterned after a Switzerland-based center for neuroscience; Offer a postdoctoral financial package that includes postdoctoral training as well as a career transition award that carries over to a junior faculty position. The final step (above) is designed to ease the often difficult transition from fellowships to faculty position. The concept of combining postdoctoral training with a career transition award is a new approach being funded and implemented in a variety of ways by industry, professional organizations, foundations, NIH institutes, and the Medical Research Council of Canada, according to several participants. Dr. Toby Behar of NINDS remarked that the concept is “probably one of the most exciting proposals I have heard ... because I think it would really work in attracting the best and the brightest and especially for the issue of the physician-clinician in training new clinician researchers.” Another advantage is that it offers stable funding for the recipient and enhances his or her attractiveness to the institution offering the faculty position. During the previous day's presentation, Dr. Stephen Hauser drew special attention to the importance of attracting young physicians to MS research. “Not only is there a national plight vis-a-vis physician scientists, but in MS we are underrepresented in attracting the best minds ... the physician scientist is the person who is connecting and sustaining the connections between the bedside and the science, be it immunology, health sciences, or health services research, ...” Hauser described a program at his institution that offers medical residents five years of funding for research together with core curricula and close mentoring. He stressed that young people are drawn to a field if they perceive the problem to be soluble and the funding to be stable. Dr. Audrey Penn of NINDS described some new NIH initiatives to recruit physicians into clinical research and expressed the desire “to partner with the National MS Society on getting people started.” Dr. Johnston described a successful recruitment program for clinician-scientists that involves a partnership between the academic pediatric community and the NIH, and that might be emulated by the MS research community. The academic pediatric societies, the American Academy of Pediatrics, and March of Dimes, formed a consortium that included the National Institute of Child Health and Human Development (NICHD) and created a program in which academic departments identify a promising resident and propose that they apply to the program. The program provides a 3-year fellowship at a good stipend that the fellow can take to any basic science laboratory in the United States. The fellow has the assurance that he or she can return to the sponsoring department at the end of the fellowship, but he or she is not required to, and that puts the onus on the sponsoring department to make an attractive offer, an offer which is enhanced by the provision of start-up faculty funds at the sponsoring department. The program has been very successful in encouraging
OCR for page 11
Page 11clinicians to pursue pediatric research and, as Dr. Johnston described, it has “generated a coterie of real leaders, really solid clinician scientists who are now distributed across American pediatrics and have been highly successful.” MS Centers and Program Projects The breakout group discussed centers of excellence as a way of creating a stimulating environment that supports a critical mass of investigators, serves as a magnet for trainees and young investigators, has discretionary funds, and can support a set of core resources, including imaging technology, statisticians, bioinformatics, and administration. They described a model from Melbourne, Australia in which an MS research center occupies one floor, Alzheimer's disease another floor, and a third floor a different discipline, all sharing core resources funded by government, local philanthropy, and industry. Some centers could be devoted to high-risk and multidisciplinary research. Although there are some MS research centers with multiple programs funded through multiple sources, there are no centrally funded MS centers today, 2 though the NIH and the National MS Society have funded MS centers in the past. Center grants were discontinued by the National MS Society because of their high, long-term cost without the benefits of sustained excellence, innovation, and productivity. To overcome these problems, the breakout group suggested greater oversight and more accountability through competitive renewal of funds every 5 years on the basis of both training and productivity. The breakout group also discussed program project grants, which support three to five interrelated research projects with central core and administrative framework. They too could be designed for high-risk, multidisciplinary projects, and include a training component, according to Dr. Ray Roos, a Committee member assigned to the breakout group. In their discussion of the proposal for MS research centers, several participants noted the lack of accountability and high investment that detracts from funding for investigator-initiated research. Dr. Celia Brosnan observed that, “they don't have that rapid response” to take advantage of new scientific leads and to support high-risk research. Dr. Paul Hoffman of the Veterans Administration pointed out that 2.5 years agothe VA invested in a new mechanism, somewhat smaller than a center, called REAPS, Research Enhancement Award Programs. These are investigator-initiated grants funded at $250,000 per year, focused on an area or a particular disease, such as Parkinson's or dementia. “The idea was to be something totally new ... to use these funds for ... pilot projects ... core facilities, and to do training ... The word out that we hear is that they have been highly successful and we are in the process of reviewing them. ...” The NIH has established various new initiatives to foster interdisciplinary collaboration that are relevant to MS research; for example, the Bioengineering Research Partnerships and Bioengineering Research Grants, which are broadly based, cross-institute awards for multidisciplinary teams to develop knowledge or methods to prevent, de- 2 With the exception of an MS center for medical rehabilitation at the University of Washington
OCR for page 12
Page 12tect, diagnose, or treat disease—including behavioral and rehabilitation research. Program project grants can be organized along multidisciplinary lines as well, according to Dr. Reingold whose organization jointly funded a program project grant with NIAID on the concept of gender and autoimmunity. The real dilemma facing funding agencies, said General Dugan of the National MS Society, is that funding of big projects comes at the expense of more widely distributed investigator-initiated projects. A question he raised was, by what criteria should centers be judged to ensure their productivity? Dr. Lisak pointed out that some centers funded by the National Cancer Institute are judged not only on the basis of their accomplishments through the center grant but also on other measures of productivity, including success with program projects, investigator-initiated grants, and clinical trials. The Dutch MS Society's recent experience with a multidisciplinary center, said Dr. Lucas, has been highly successful in stimulating more grant applications, publications, and post-docs than would have occurred with separate funding streams. The VA had been skeptical of the value of a center, noted Dr. Hoffman. But they decided to proceed cautiously with REAPs once they had identified highly focused problems that could only be addressed by some type of center. They plan to perform a careful evaluation of the program according to the criteria developed by the center applicant. “We are willing to partner at the VA ... we are very interested in expanding our funds to expand the whole pool, but we don't want to be duplicative.” Dr. Reingold commented that centers represent opportunities and risks that might be more palatable if they were shared across funding agencies. Dr. Behar of NINDS questioned whether a center has advantages over a program project. Yet she pointed to the value of a center targeted to a particular problem (e.g., the need for translational research) rather than focused on a particular disease. When Dr. Behar asked what type of center of excellence is recommended by the workshop, Dr. Hauser replied that there was “one clear need ... for a network of dedicated imaging facilities.” Several participants had highlighted the lack of uniformity or standardization in imaging, which precludes sharing of data, and the need for surrogate markers to assess the progression of MS. Dr. Wolinksy called for four to six regional centers of “imaging excellence” with unlimited use of scanner time and an excellent network to provide “cross-sectional longitudinal data across all subtypes of MS with multimodal imaging that is highly integrated with the occasional pathological correlate.” Clinical Trials Network To increase research efficiency (#16), the breakout group supported the establishment of a network of clinical trials with the following goals: to link up clinical investigators, avoid duplication of effort, provide for quality control, clarify diagnoses, and develop standardized measures for clinical trials outcomes. “There was a feeling among the group that this was an idea whose time had come,” said Christine Purdy, the group's rapporteur. In the discussion, Dr. Wolinsky reported that the Clinical Trials Commit-
Representative terms from entire chapter: