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 1
Page 1 Executive Summary Multiple sclerosis (MS) is a complex disease that has been much more difficult to cure than was expected when the National Multiple Sclerosis Society (the MS Society) was founded in 1946 by Sylvia Lawry “to end the devastating effects of multiple sclerosis.” Yet optimism is possibly greater than it has ever been since those early years, in large part due to the development of the first treatments that can slow the progress of MS. Services for people with MS have also improved. “Diagnose and adios,” Labe Scheinberg's famously disparaging quote about the options available to MS neurologists in the 1970s, no longer rings true. Nor does the advice to young researchers that “if you want to ruin your career, go into MS.” Much has changed since 1946. Still, no cause or cure for MS has been found. It remains a mysterious disease with no known pathogen or even known determinants of its severity and course. MS is not alone in this regard. Neurological diseases are among the most difficult to study, and although beneficial therapies have been developed in the last decades for Parkinson's disease, Alzheimer's disease, and epilepsy, there is still no cure for any of the degenerative neurological diseases. Advances on key fronts, such as improved ability to create images of the living brain and spinal cord, new understanding of the brain's capacity for repair, and an overall accelerated pace of new discoveries about the cellular machinery of the brain, have renewed the optimism of many investigators about the possibility of developing effective therapeutic strategies for MS patients. New therapeutic strategies, such as gene therapy, stem cell transplantation, and neuroprotection strategies, rising on the horizon have emerged from recent advances in these areas.
OCR for page 2
Page 2 Over the years, the specific targets of MS research have been refocused and revised. The MS Society has reconsidered and remained committed to its focus on research. At the same time, the scope of research topics has expanded, as have perspectives of the Society's role. Although MS research has traditionally been conducted on behalf of patients who remained in the background, now—to a small, but increasing degree—patient perspectives have stimulated new areas of research. New disciplines have emerged. Health care policy, functional status measurement, and quality-of-life assessment are all relatively new areas of research and are critically important for improving the lives of people with MS. The spectrum of current MS research ranges from strategies to develop treatments that impede the disease process, to treatments for specific symptoms, to research aimed at promoting successful adaptations to the illness, including optimizing the abilities of people with MS to function in their daily lives. In December 1998, the National Multiple Sclerosis Society asked the Institute of Medicine to undertake a strategic review of MS research on its behalf. This report presents the research strategies and programs that the committee believes are likely to be the most productive and most important in the near future. Throughout the study, the committee sought to identify windows of opportunity for research, such as those created by new discoveries about the self-repair mechanisms of the brain or new disease-specific changes in gene activation. The committee also sought to identify research needs where the windows of opportunity are less transparent, such as the development of evidence-based approaches to address varied information needs of people with MS and to treat the fatigue and pain that so often accompany MS. Ideas for the future are built on the review of current knowledge and gaps in the biomedical and social science of MS. The intended audience of this report includes the architects and developers of MS research programs, as well as people with MS and their families who want to learn what is currently known about MS and what might lie ahead. The report covers three broad areas: (1) biomedical aspects of the disease, causes, course, and treatments (Chapter 2, Chapter 5, and Chapter 6); (2) adaptation and management (combination of medical, technological, and psychosocial aspects) (Chapter 3 and Chapter 4); and finally, (3) proposals for research managers to facilitate research progress (Chapter 7). DISEASE CAUSES, COURSE AND TREATMENTS The ultimate goal of research in MS is the development of interventions that can improve the lives of those living with MS and can prevent or cure MS. However, understanding of the MS disease process is not yet sufficient to predict which therapeutic strategies will be most effective. Although the new disease-modifying drugs are a major leap forward, it is important to remember that they are not a cure, nor are they effective for all patients. The recommendations
OCR for page 3
Page 3described below summarize the committee's conclusions about which directions appear most likely to provide the fundamental knowledge that can lead to the development of effective therapies (see Box 1 for summary). RECOMMENDATION 1: Research on the pathological changes underlying the natural course of MS should be emphasized, because it provides the key to predicting disease course in individual patients, understanding the physiological basis of MS, and a basis for developing improved therapeutic approaches. Unpredictability imposes a particularly acute burden on people with MS. They have no way of knowing when a relapse will occur, how impaired they will be, or whether they will recover from the relapse. Yet it is now clear that disease activity precedes relapses. Understanding these pathological changes is the first step toward predicting—at least in the short term—disease progression in individual patients. Research on the natural course of MS would include defining the relationship between cellular and molecular changes and the progression of disability, as well as determining the physiological basis for different clinical manifestations of MS. Changes in gene expression should be analyzed in individual cell types, particularly those in and at the borders of lesions. Such information will also improve the ability to develop more refined diagnostic tools, provide benchmarks against which to measure the effect of therapeutic interventions, and provide the scientific basis to identify new therapeutic approaches. Research on pathological changes occurring early in the disease should be particularly emphasized. This should also include the development of improved diagnostic criteria (most likely, criteria based on neuroimaging) that allow early and more accurate diagnoses of MS. If aggressive treatment is to be instituted at the onset of disease, early and accurate diagnosis is especially important. RECOMMENDATION 2: Research should be pursued to identify how neurons are damaged in MS, how this damage can be prevented, and how oligodendrocytes and astrocytes are involved in damage and repair processes. Oligodendrocytes, astrocytes, and neurons can, in a sense, all be regarded as the cellular “victims” in multiple sclerosis. It is clear that oligodendrocytes and the myelin sheaths they form are damaged, astrocytes respond by forming a glial scar, and in some cases, axons (outgrowths of neurons) degenerate in MS. However, a better understanding of the neuronal response to injury and capacity for repair, the capacity of myelin-forming cells to remyelinate neurons and restore function, and the contribution of astrocytes is essential to deciphering the neuropathology of MS. Although much is known, many questions remain, and their answers have important implications for therapy.
OCR for page 4
Page 4 BOX 1 Recommendations for Research on Causes, Course, and Treatments Recommendation 1: Research on the pathological changes underlying the natural course of MS should be emphasized, because it provides the key to predicting disease course in individual patients, understanding the physiological basis of MS, and a basis for developing improved therapeutic approaches. Recommendation 2: Research should be pursued to identify how neurons are damaged in MS, how this damage can be prevented, and how oligodendrocytes and astrocytes are involved in damage and repair processes. Recommendation 3: The genes that underlie genetic susceptibility to MS should be identified, because genetic information offers such a powerful tool to elucidate fundamental disease processes and prognosis, and to develop new therapeutic approaches. Recommendation 4: Because the discovery of an MS pathogen would likely provide the single most important clue for identifying effective treatments, this search must remain a high priority, but it should be conducted using powerful new and efficient methods. Recommendation 5: Research to identify the cascade of immune system events that culminates in the destruction of myelin should remain a priority. Recommendation 6: The power of neuroimaging as a tool for basic research and for clinical assessment should be taken advantage of more extensively. Recommendation 7: Animal models should be developed that more faithfully mirror the features of MS and permit the analysis of how specific molecules and cells contribute to the disease process. Recommendation 8: Strategies for protection and repair of neural cells, including the use of neuroprotective factors as well as stem cells, hold great promise for the treatment of MS and should be a major research priority. Recommendation 9: New, more effective therapeutic approaches to symptom management should be pursued, including those directed at neuropathic pain and sensory disturbances. Recommendation 10: In the absence of any fully effective therapies, integrated approaches for the delivery of currently available therapeutic agents should be investigated. Recommendation 11: Better strategies should be developed to extract the maximum possible scientific value from MS clinical trials.
OCR for page 5
Page 5 RECOMMENDATION 3: The genes that underlie genetic susceptibility to MS should be identified, because genetic information offers such a powerful tool to elucidate fundamental disease processes and prognosis, and to develop new therapeutic approaches. Compelling data indicate that MS is a complex genetic disorder. The identification of susceptibility genes for MS represents a significant challenge but also a major opportunity to elucidate the fundamental disease process. Genetic discoveries are likely to contribute to a better understanding of heterogeneity, clinical course, prognosis, and response to therapy. Even the discovery of a new gene with a very small genetic effect on MS could have major implications for the development of entirely new therapies based on the genetic mechanism. The committee believes that an aggressive effort in human genetics is essential. The critical importance of identifying rare families with monogenic variants of MS cannot be overstated; this approach has been extraordinarily fruitful in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. RECOMMENDATION 4: Because the discovery of an MS pathogen would likely provide the single most important clue for identifying effective treatments, this search must remain a high priority, but should be conducted using powerful new and efficient methods. Conventional tissue culture approaches to isolate pathogens in MS have consistently failed to find any convincing result, possibly because some pathogens do not grow in tissue culture. Newer approaches should be used, such as those that involve the identification of genomic information relevant to the pathogen and those that have the potential to reveal a broader range of pathogens than are detectable in tissue culture. The methods include polymerase chain reaction (PCR), representational difference analysis, and sequence screening using the host immune response. These powerful new methods have not yet been applied to investigations of MS tissues in any concerted and organized way, and their use should be a high priority. Discovery of a trigger for the first MS event would likely provide the single most important clue for identifying a cure and means of prevention. This event might precede clinically observable symptoms and might be different from the events that drive subsequent autoimmune attacks. Thus, despite the long and thus far unsuccessful search, research to identify the trigger event(s) of MS must remain a high priority. RECOMMENDATION 5: Research to identify the cascade of immune system events that culminates in the destruction of myelin should remain a priority. The most striking pathology in MS is the immune system's attack and destruction of the body's own myelin sheath. What causes the immune system to attack myelin is unknown. Although myelin basic protein (MBP) might trigger a
OCR for page 6
Page 6particularly vigorous autoimmune response, it is not the only autoantigen, nor does it account for the full autoimmune response. Any brain protein is a potential autoantigen, although not all are equal in their consequences. Two critical foci for research in the immunopathology of MS include: identification of the most important autoantigen triggers for autoimmune responses in MS and increased understanding of pathogenic immune cells. One of the first pathological processes leading up to MS attacks is thought to be activation of autoreactive T lymphocytes, or T cells, and their migration into the central nervous system. However, T cells and the inflammatory molecules they secrete are not the only players. Many cells and molecules of the immune system—likely unleashed by T-cell activation—participate in demyelination. The entire cascade of immune system events eventually culminates in myelin destruction. The key features of this cascade are not fully understood, including the precise ordering of events, the precise antigens targeted by T cells, and the precise contributions of B lymphocytes and other cells of the immune system. RECOMMENDATION 6: The power of neuroimaging as a tool for basic research and for clinical assessment should be taken advantage of more extensively. Neuroimaging is an invaluable adjunct to clinical exam and patient reports for evaluating the effects of therapeutic intervention. Research should emphasize the application of various accepted and evolving neuroimaging techniques to understand the evolution of MS lesions from pre- or asymptomatic stages through the progression to permanent tissue alteration or recovery from disability. Understanding of the MS disease process will be enhanced by expanded use of imaging techniques such as magnetic transfer imaging (MTI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) scanning. RECOMMENDATION 7: Animal models should be developed that more faithfully mirror the features of MS and permit the analysis of how specific molecules and cells contribute to the disease process. An animal model for a particular disease or condition can provide the understanding to design therapies based on biological knowledge, rather than shotgun testing. For example, mouse models with targeted mutations in the cystic fibrosis gene are providing a means for testing gene therapy delivered by aerosol into the lungs. Characterization of mouse models of various dwarfing syndromes, cloning of mutated genes, and parallel comparative genetic mapping and cloning of genes for similar human syndromes have led to an understanding of various human dwarfing conditions.
OCR for page 7
Page 7 Generation of a reliable animal model of MS has been a long-standing goal in MS research. Current animal models of MS fall into a group of diseases like experimental autoimmune encephalomyelitis (EAE) and animal models of virus-induced demyelination. Although the models that are presently available have yielded a tremendous amount of information relevant to MS, better animal models can be developed. Key advantages of current animals models include the fact that the initiating trigger is known, the exact time of the initiating event is known, a great deal is known about the genetics and the immune system in the case of rodents, and finally, the availability of animal mutants with “knockouts” of genes for particular arms of the immune system or those that carry a transgene perturbing a protein that is relevant to MS. A key disadvantage of available models is that they do not replicate the cellular or molecular pathology of MS. Some types of EAE, for example, produce brisk demyelination, whereas others produce little demyelination. In addition, these models are not very tractable for studies of the electrophysiology and biophysics of neuronal function, a serious limitation in a disease such as MS in which symptoms and signs arise from impaired nerve function. RECOMMENDATION 8: Strategies for protection and repair of neural cells, including the use of neuroprotective factors as well as stem cells, hold great promise for the treatment of MS and should be a major research priority. Specific neuroprotective strategies to be investigated include: elucidation of the pathways leading to cell death in the central nervous system; identification of neuroprotective and repair strategies that will reduce or repair axonal injury; development of therapeutic approaches that will induce restoration of conduction in demyelinated axons, for example, by inducing expression of appropriate densities of the appropriate subtype(s) of sodium channels among them; development of approaches to stimulate re-growth of damaged axons; and development of systems for the delivery of neuroprotective and repair factors to the central nervous system. An effective delivery system is an essential link in the development of neuroprotective or restorative therapies. Thus, the development of such delivery tools, for example, cells that have been genetically engineered to produce specific neuroprotective factors, or molecular packaging systems, is a high priority. Specific goals to identify the cellular and molecular pathways that control the death of myelin-forming oligodendrocytes include the identification of the following:
OCR for page 8
Page 8 therapeutic strategies that can protect oligodendrocytes from immune attack; strategies to activate endogenous oligodendrocyte precursor cells to promote remyelination (endogenous stem cells); and strategies for the transplantation of myelin-forming cells into the demyelinated CNS. This includes using precursor cells or genetically engineered cells (exogenous stem cells). The last two strategies must be considered in the context of the specific features of MS. For example, newly formed myelin might be destroyed through the same immune response that destroyed the original myelin. RECOMMENDATION 9: New, more effective therapeutic approaches to symptom management should be pursued, including those directed at neuropathic pain and sensory disturbances. The pathophysiology of pain and paraesthesia in MS is not understood. Although neuronal hyperexcitability appears to underlie these symptoms, it is not known why it occurs in MS. The cellular and molecular basis for neuronal hyperexcitability in MS should be investigated. Molecular targets should be identified; for example, inappropriately expressed ion channels that cause abnormal impulse trafficking in MS. After identification of such targets, pharmacological methods can be developed for regulating the activity of these critical molecules. The impact of electrical activity within neurons and of exercise and physical therapy should be investigated in regard to disease progression and functional capacities. This will require the development of better tools to measure function. RECOMMENDATION 10: In the absence of any fully effective therapies, integrated approaches for the delivery of currently available therapeutic agents should be investigated. Since there are, as yet, no treatments that cure MS or halt disease progression entirely, it is important to develop integrated approaches to testing those agents that can at least modify the course of the disease. Such trials are expensive and lengthy, and they require large numbers of patients. Agents of different classes will have to be tested in sequence and in combination. Such trials are also best done when the dose range and safety profile of each individual agent to be employed in the trial are known, and the potential for adverse drug interactions should be carefully monitored. Separate end points might be required for each agent as appropriate to its individual pharmacological profile. Most importantly, standardized protocols and assessments will have to be devised and agreed upon, including Phase II studies that will allow abandonment of ineffective combina-
OCR for page 9
Page 9tions before incurring the time, expense, and exposure to risk that are inherent in large, multicenter efficacy trials. RECOMMENDATION 11: Better strategies should be developed to extract the maximum possible scientific value from MS clinical trials. The committee noted that many of the pivotal MS clinical trials on disease-modifying therapies were terminated early, usually because of predetermined stopping rules, and, thereby, lost unique opportunities to obtain critical data. Although it is not generally feasible for voluntary health organizations such as the National MS Society to lead their own clinical trials, they can and should continue to play an advisory in the design of large-scale clinical trials. DISEASE ADAPTATION AND MANAGEMENT At the moment of being diagnosed, the patient is forever transformed into a “person living with MS.” Even in the absence of signs or symptoms, this person will forever after live with the knowledge that he or she can be unpredictably impaired. Sometimes a person will recover, sometimes not. For most people, living with MS will become one of the major challenges of their life. Given the millions of people currently living with MS, and those expected to do so in the future, it is important that the focus on curing MS not come at the expense of efforts to address the disruptions that pervade routine daily activities, personal relationships, family life, work responsibilities, and social involvement. Improving the lives of people with MS rests on better understanding of both their needs and their successes, specifically research into the conditions of life with MS, which requires objective, reliable research tools. The most essential tools are the various survey instruments that measure abilities to function and quality of life, which are discussed in the latter part of this chapter. These tools not only provide for objective assessment of the needs of people with MS, but also are an essential element of measuring the effectiveness of any sort of therapeutic intervention—be it a rehabilitation process, a self-help program, or a disease-modifying therapy. Quality-of-life measures can also reveal aspects of the disease process that are not readily captured in standard clinical measures and can often provide more sensitive outcome measures of the clinical efficacy of new therapies. Perhaps most importantly, they measure the outcomes that concern patients the most (see Box 2 for summary). RECOMMENDATION 12: Health status assessment methods for people with MS should be further developed and validated to increase the reliability and power of clinical trials and to improve individual patient care.
OCR for page 10
Page 10 BOX 2 Recommendations on Disease Adaptation and Management Recommendation 12: Health status assessment methods for people with MS should be further developed and validated to increase the reliability and power of clinical trials and to improve individual patient care. Recommendation 13: Research strategies aimed at improving the ability of people with MS to adapt and function should be developed in partnership with research practitioners, managers, and patients; toward this end, a series of forums to identify the most pressing needs experienced by people with MS should be convened. Quantifying health status, including functional status and quality of life, for persons with MS is essential for several reasons. Given the chroicity and uncertain course of MS, tracking its impact over time can assist with care of individual patients, suggesting near-term prognoses and the need for various interventions. Tabulating these findings across individuals offers insight into the burden of MS-related disability within populations, information increasingly used to set research, health, and social policy priorities. Longitudinal studies of the trajectory of functioning and quality of life should help to define the natural history of the disease and expand understanding of its clinical epidemiology and patterns of progression. Finally, functional status and quality of life are critical end points in measuring the effectiveness of therapy, both for clinical trials and for routine patient care. Clinical neurology should move toward adopting as a standard of care a concise measurement of health status that includes quality-of-life measures, as well as impairment and disability measures. This could serve as the basis for communication between physicians and other caregivers and for increasing the efficiency and thoroughness of consultations between patients and physicians, particularly if filled out by patients before meeting with the physician. If longterm records of such data were maintained in a data registry, they would also provide much-needed insights into the natural course of the illness. Individual records would provide information about patient health that would not normally be collected in routine clinical exam. The development and validation of new impairment and disability measures should continue to be supported. Validation of the MS Functional Composite Scale should continue, particularly to measure its sensitivity to changes in patient condition over time. RECOMMENDATION 13: Research strategies aimed at improving the ability of people with MS to adapt and function should be developed
OCR for page 11
Page 11 in partnership with research practitioners, managers, and patients; toward this end, a series of forums to identify the most pressing needs experienced by people with MS should be convened. The goal of such forums would be to define research needed to identify ways to help people with MS adapt to the illness and enhance their ability to function. The committee did not include the expertise to develop a research agenda to meet needs as experienced by patients. Indeed, there is such a small body of empirical research on this topic that the committee felt it was perhaps premature to specify the most appropriate research strategies. Rather, the committee recommends that the MS Society work in partnership with people with MS to guide the development of specific research strategies that will identify the most effective approaches toward improving their everyday lives. A series of forums could provide the needed perspective to defining those research strategies and should include the following constituencies: patients and their families; health care providers; allied health professionals, such as physical therapists, occupational therapists, and social workers; health services researchers, including survey scientists and clinical epidemiologists; social scientists, including sociologists, anthropologists, and psychologists; and representatives of organizations of patients with other disorders that present some of the same challenges faced by people with MS. The MS Society should identify specific individuals, including those whose work focuses on related issues outside the field of MS. Since the research community that deals with these issues is so small and has so many fewer funding resources than biomedicine, it is essential to look more broadly for resources. The needs of people with other chronic, debilitating diseases have much in common with those of people with MS. The MS Society should work with other relevant societies and government funding agencies to identify the most important research questions to address the goal of improving the lives of people with chronic and debilitating diseases, such as MS. New strategies are needed to improve dissemination of the latest research information and the best methods of informing patients so they can take the fullest advantage of treatment options and available assistance. This includes developing a better understanding of the most effective timing, settings, and modes of delivering information. Some information is important to deliver at the time of diagnosis (for example, what to expect in the next few years, how to ensure health care); other information is only of interest to patients much later in
OCR for page 12
Page 12the disease course (for example, how to obtain and choose a wheelchair). Modes and settings are also important determinants of effective communication. Certain information is best imparted by a health care provider during a private, scheduled visit; other information is best gained in a group setting. Some information has to be processed and molded to fit individual needs, and this is often accomplished more effectively in the back-and-forth exchange of a group setting. Uses of computers, including the Internet and chat groups, should be researched. RESEARCH MANAGEMENT The foundations of scientific progress are laid in the building and maintenance of the research enterprise. In simplest terms, this means getting the “right” people in the “right” places, and this is the essential role of research managers (see Box 3 for summary). RECOMMENDATION 14: New researchers should be actively recruited to work in MS, and training programs should be designed to foster BOX 3 Recommendations to Build and Support the MS Research Enterprise Recommendation 14: New researchers should be actively recruited to work in MS, and training programs should be designed to foster productive interactions with established investigators both within and outside the MS research community. Recommendation 15: Concerted efforts should be made to stimulate enduring interdisciplinary collaborations among researchers in the biological and non-biological sciences relevant to MS and to recruit researchers from other fields into MS research. Recommendation 16: Programs to increase research efficiency should be developed, including collaborations to enable expensive large-scale projects (e.g., clinical trials, genome screens) and to organize collection of scarce resources (e.g., human tissue). Recommendation 17: New strategies should be developed to encourage more integration among the different disciplines that support and conduct research relevant to improving the quality of life for people with MS. Recommendation 18: To protect against investing research resources on false leads, there should be an organizational structure to promote efficient testing of new claims for MS pathogens and disease markers.
OCR for page 13
Page 13 productive interactions with established investigators both within and outside the MS research community. In the last few decades there has been a tremendous influx of talented researchers into the field of neuroscience. Yet committee members observed that this burgeoning pool of researchers has not been drawn to MS research in the same numbers as they have to other neurological diseases. To bring new researchers into MS, it is not enough to rely on those who have already shown an interest in it. Active outreach is necessary. Funding new researchers is of little value without the ability to sustain the investment. Attracting new researchers should be balanced with reasonable expectations that successful researchers can continue. In the 1990s, more Ph.D.s were awarded than could be employed in research. During such periods, recruitment efforts by private research foundations might be more productive if they were to shift the balance of their efforts towards reducing support for training Ph.D. students and increasing their efforts to recruit and support postdoctoral fellows. RECOMMENDATION 15: Concerted efforts should be made to stimulate enduring interdisciplinary collaborations among researchers in the biological and non-biological sciences relevant to MS and to recruit researchers from other fields into MS research. Concerted efforts should be made to stimulate enduring cross-pollination among the different research areas relevant to MS. It is not enough to bring in researchers from other fields to participate in isolated workshops. Rather, sustained interactions that promote productive collaborations or the development of new ideas must be fostered. The committee felt that giving a small amount of funding (for example, $100,000) to an established laboratory, which has been done in the past, is not enough to encourage researchers to pursue MS research. Programs to encourage cross-pollination should target individual researchers. This has been tried successfully by other private health foundations (for example, the Hereditary Disease Foundation, CaP CURE, and the ALS Association). More cross-talk between clinical and basic scientists is needed. One means of stimulating more exchange between basic researchers and clinicians would be to provide special funding for sabbaticals in which basic scientists could work with clinicians. There was a sense among the committee that MS has attracted less interest from basic neuroscientists than other neurological diseases. This should be actively encouraged by organizing symposia at scientific meetings, such as those of the Society for Neuroscience where MS research has received relatively little attention. RECOMMENDATION 16: Programs to increase research efficiency should be developed, including collaborations to enable expensive large-scale projects (for example, clinical trials, genome screens)
OCR for page 14
Page 14 and to organize collection of scarce resources (for example, human tissue). The committee recommends that the MS Society consider exploring less conventional approaches such as those tried by other health care foundations. The MS societies should consider leading an effort to identify and develop successful models of collaboration. Although these societies cannot fund many clinical trials, it might be able to work as a catalyst to facilitate more effective, far-reaching clinical trials, for example, by bringing together the right people. This would also include the development of data registries that would apply to natural history studies and long-term therapeutic evaluations. RECOMMENDATION 17: New strategies should be developed to encourage more integration among the different disciplines that support and conduct research relevant to improving the quality of life for people with MS. This would include research on the instruments used to assess quality of life, employment issues, personal independence, and the identification of optimal models of caring for people with MS. Research in these areas has too often proceeded in parallel paths with little apparent recognition of the work of others. For example, many articles about the psychosocial aspects of MS are published in nursing, psychology, physiotherapy, and neuroscience journals, and yet they often fail to cite articles on the same topic published outside their professional disciplines. Because the health policy research field is relatively small and research funds are limited, partnerships should be developed among MS societies and with other health research organizations that target diseases that confront patients with similar challenges. Although each of these diseases has some unique features, for the most part, the research techniques, patients' needs, and even the investigators themselves overlap across different diseases, particularly chronic, debilitating diseases. Examples of such diseases include rheumatoid arthritis, diabetes, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). Much of the research on quality-of-life issues for any of these diseases is likely to be relevant to people with MS. Indeed the development of partnerships among the related health care organizations should benefit a far greater number of patients than each could serve alone. Partnerships could take a variety of forms from collaborative development and funding of requests for proposals (RFPs) to collaborations in convening symposia and workshops. RECOMMENDATION 18: To protect against investing research resources on false leads, there should be an organizational structure to promote efficient testing of new claims for MS pathogens and disease markers.
OCR for page 15
Page 15 Over the years, various viruses, bacteria, and toxins have been proposed as possible causes of MS. None of them have withstood the scrutiny of careful research, although, in a few cases, they have not been ruled out as causes. Although erroneous claims in MS research are relatively rare—there have been fewer than five in the last five years—their effects can be far-reaching. In some cases, erroneous claims have misdirected research, resulting in a substantial but unproductive investment in time and money. These erroneous claims have also led to the treatment of patients with inappropriate, expensive, and potentially harmful therapies. For example, the claim that metal toxicity causes MS induced some patients to have teeth extracted and amalgam fillings removed. New claims of MS pathogens, when appropriate, should be resolved as quickly as possible. The MS societies are the most likely organizations to undertake such tests of newly proposed pathogens on an ad hoc basis. One possible approach is that following a potentially credible claim implicating a particular pathogen in MS, a society could oversee a project whereby the investigator making the claim, as well as an expert in the particular pathogen, could review clinical samples. A similar approach could be taken in terms of other claims related to diagnosis or treatment of MS in situations in which a quick confirmation of the results would be important to MS patients or to the neurological and scientific community. This approach should reduce costs to patients, researchers, and even the MS societies. The key elements of such a program would be: evaluation of credible claims that are judged to have the potential for influencing research strategies or treatments, rapid response, and generation of replicate data sets, necessary for establishing the reliability of claims. If the validation experiments were conducted in established laboratories equipped with the necessary expertise and research tools, the costs should be relatively low. It might also be possible to offer the possibility of confirming such path-breaking claims prior to their initial publication in order to increase the immediate impact of the discoveries or spare investigators embarrassment should their data be incorrect.
OCR for page 16
Representative terms from entire chapter: