Canadian Multiple Sclerosis Monitoring System: Environmental and Technical Scan

Transcription

1 pic pic pic Canadian Multiple Sclerosis Monitoring System: Environmental and Technical Scan Standards and Data Submission

2 Our Vision Better data. Better decisions. Healthier Canadians. Our Mandate To lead the development and maintenance of comprehensive and integrated health information that enables sound policy and effective health system management that improve health and health care. Our Values Respect, Integrity, Collaboration, Excellence, Innovation

3 Table of Contents Acknowledgements... iii Disclaimers... iii Executive Summary... v About This Report... vii Multiple Sclerosis A Complex Disease... 1 The Search for a Cause... 2 Diagnosis... 4 Treatment... 7 Areas of Research... 8 Health Services and Care for People Living With MS in Canada Overview of Initiatives in Canada Public Health Agency of Canada Statistics Canada Health Canada Canadian Agency for Drugs and Technologies in Health Multiple Sclerosis Society of Canada Canadian Institutes of Health Research Rx&D Health Research Foundation Provincial and Regional Initiatives Overview of International Initiatives World Health Organization European Committee for Treatment and Research in Multiple Sclerosis Americas Committee for Treatment and Research in Multiple Sclerosis Latin American Committee for Treatment and Research in Multiple Sclerosis Pan-Asian Committee for Treatment and Research in Multiple Sclerosis Multiple Sclerosis International Federation International Organization of Multiple Sclerosis Nurses National Multiple Sclerosis Society Consortium of Multiple Sclerosis Centers Rehabilitation in Multiple Sclerosis The European Multiple Sclerosis Platform Current State of MS Data Collection Data Standards and Classifications... 27

4 Existing MS Databases and Registries Canadian and International Internal Scan of CIHI Data Holdings Canadian Landscape Preliminary Findings of the Technical Scan Canadian Network of Multiple Sclerosis Clinics Settings and Services Technical Infrastructure Data Management Key Aspects A National MS Monitoring System for Canada Summary Appendix A: List of Canadian Network of Multiple Sclerosis Clinics (as of October 19, 2011) Appendix B: Public Health Agency of Canada MS-Related Projects Within the National Population Health Study of Neurological Conditions, 2010 to Appendix C: Overview of MS Research Funded by the Multiple Sclerosis Society of Canada, Appendix D: Seven Operating Grants Provided by the Multiple Sclerosis Society of Canada and the National MS Society (U.S.) to Investigate the Relationship of CCSVI to Multiple Sclerosis Appendix E: Total Grant Amounts Funded by the Canadian Institutes of Health Research to MS-Related Projects, by Fiscal Year Appendix F: MS-Related Projects Funded by the Canadian Institutes of Health Research, Fiscal Year (as of July 13, 2011) Appendix G: Overview of Canadian and International Multiple Sclerosis Data Systems References ii

5 Acknowledgements Production of this environmental and technical scan has been made possible by a financial contribution from the Public Health Agency of Canada. Numerous individuals and organizations contributed to the development of this environmental and technical scan in various ways providing information, sharing experiences and learnings and/or validating facts. The Canadian Institute for Health Information would like to express utmost gratitude to the many contributors who played a role in the development of this environmental and technical scan. Disclaimers The views expressed herein do not necessarily represent the views of the Public Health Agency of Canada. This environmental and technical scan was conducted between May 1, 2011, and July 31, It is intended to provide an overview and is not an exhaustive list or comprehensive in nature. iii

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7 Executive Summary The objective of this environmental and technical scan was to acquire strategic intelligence and gain a better understanding of current activities and changes taking place nationally and internationally related to the development and maintenance of data systems for multiple sclerosis (MS). The scan also allowed the Canadian Institute for Health Information (CIHI) to identify opportunities and challenges for the future direction of the Canadian Multiple Sclerosis (MS) Monitoring System. The knowledge gained will be incorporated into planning and decisionmaking activities related to the development of the Canadian MS Monitoring System. MS is a complex disease with many uncertainties: unknown cause, no known cure and unpredictability of symptoms. The debilitating nature of this disease and its impact on the quality of life for people living with MS, their families and caregivers is often significant. Although the total financial amount being devoted to MS research and analytical activities is not explicitly stated, it is evident by looking at some of the key initiatives currently under way that considerable time, effort and funding are being spent to help elucidate the uncertainties around the disease. Given what we know and do not know about MS, it will be important to build a data collection system that is flexible and that can accommodate a changing and dynamic environment. While achieving this goal will be challenging, other countries are experiencing similar challenges and are moving in a similar direction. Much data is being collected about MS in Canada and internationally. In Canada, there is a focus on specific research questions and/or sub-populations. It is envisioned that the development of the Canadian MS Monitoring System will provide a more comprehensive national picture of MS by filling existing information gaps, particularly related to clinical information, that are not covered by initiatives currently being pursued in Canada. Data collected by the MS clinics within the Canadian Network of Multiple Sclerosis Clinics has generally evolved to meet local research or administrative needs. Across the various data collection initiatives in Canada, there is no common data standard; rather, a variety of data collection tools, methods and technologies are being employed. However, the Expanded Disability Status Scale (EDSS) 1 was broadly used across the MS clinics to measure functional status and disease course, which was generally collected according to recognized standards. There is an opportunity to standardize data collection to enable data to be comparable and pulled together to help inform the national picture. Although there is no internationally recognized standard minimum data set for MS, there is an initiative under way to help standardize the collection of data: the National Institutes of Health s National Institute of Neurological Disorders and Stroke Common Data Element Project. This project should be taken into consideration when developing the Canadian MS Monitoring System. v

8 There is an opportunity to provide real insight into MS across the continuum of care by linking the data captured by the Canadian MS Monitoring System with other MS-related data sources. Within CIHI alone, there are a number of potential opportunities for data linkage, including with emergency and ambulatory care, acute inpatient care, rehabilitation, continuing care, home care and prescription drug information. Development of a national monitoring system for Canada will not be without its challenges. One of the most significant issues facing the Canadian MS Monitoring System is participation. As observed with similar international initiatives, participation will be key to achieving a comprehensive data set for Canada. The Canadian Network of Multiple Sclerosis Clinics the proposed data providers for Phase I of the Canadian MS Monitoring System already faces heavy workloads and struggles with resource constraints, especially data management resources. Therefore, developing a system that incorporates ease of use, avoids duplication of efforts and minimizes burden will be critical. For the monitoring system to be successful, it must meet the information needs of its stakeholders, including clinicians, researchers, health policy developers, patients and the public. When implemented, it can be an important tool to help patients, clinicians, researchers and the public better understand disease patterns across Canada, variation in use of treatments and long-term patient outcomes, as well as support quality improvement in services and resource use. A national data collection system could also facilitate international comparisons to help inform the global view of MS. vi

9 About This Report The objective of this environmental and technical scan is to gain an understanding of the current environment to inform decision-making and planning for the Canadian MS Monitoring System. Environmental scanning is useful for identifying opportunities and challenges for consideration in the future direction of a project. This environmental and technical scan was conducted between May 1, 2011, and July 31, This report summarizes key MS-related initiatives and research both within Canada and internationally. It also presents information on current MS data collection activities, including data systems, technology and data standards. This report is intended to be a high-level document to facilitate discussion and inform decisionmaking as CIHI develops and implements the Canadian MS Monitoring System with the support and advice of various stakeholders and experts. It is not intended to be an exhaustive list or a comprehensive, detailed summary. The report is divided into the following sections: Multiple Sclerosis A Complex Disease Overview of Initiatives in Canada Overview of International Initiatives Current State of MS Data Collection Canadian Landscape Preliminary Findings of the Technical Scan Summary The information presented in this document was accumulated through a review of available literature and engagement with the key stakeholders including site visits, teleconferences and personal communications. vii

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11 Multiple Sclerosis A Complex Disease Multiple sclerosis, described by Jean-Martin Charcot in 1868, is a chronic neurological disease that affects approximately 2 million people worldwide. 2 It is the most common cause of neurologic disability in young adults in the Western world. 3 Canada has one of the highest estimated prevalence of MS in the world, 4 with an estimated 55,000 to 75,000 people in Canada living with the disease. 5 There are strong geographical patterns to MS, with a higher frequency of MS in populations at a greater distance from the equator. 4 The typical age of onset of MS is between 20 and 40 years of age, with a female-to-male ratio now exceeding 3:1. 6 MS is a complex disease affecting the central nervous system, which comprises the brain, spinal cord and optic nerves. For reasons yet unknown, immune cells attack and destroy the insulating layer (myelin) surrounding neurons that help electrical signals pass between the brain and the rest of the body. The nerve fibres themselves may also be damaged. Patches of scar tissue, called sclerosis, form. When any part of the myelin sheath or nerve fibre is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing the variety of symptoms that can occur. 7 MS is a chronic, often disabling disease that has a significant impact on those people living with MS, their family and caregivers. The severity of MS can vary from very mild, with almost no disability and effort on daily activities, to malignant, in which the disease progresses rapidly, resulting in multiple neurological disabilities or death within a short time after disease onset. 8 MS also has a significant economic cost on society. The Global Economic Impact of Multiple Sclerosis report, produced by the Multiple Sclerosis International Federation, indicated that MS imposes substantial economic burdens on MS patients, on their families, and on society as a whole. Moreover, these burdens span a broad range of impacts, including prevalence of MS, direct costs, indirect costs, QOL (quality of life), and other intangible costs. 2 The Burden of Neurological Diseases, Disorders and Injuries in Canada, a 2007 report produced by the Canadian Institute for Health Information (CIHI), concluded that MS accounted for $139.2 million in direct costs and $811.3 million in indirect costs in Canada in MS is associated with a wide variety of symptoms, affecting different parts of the body and with varying severity. 10 Symptoms differ greatly between individuals and can be very debilitating and impact the quality of life of individuals with MS. Common symptoms of MS include visual disruptions, balance and coordination problems, spasticity, altered sensation, fatigue, pain, 2, 8, 11 bladder and bowel problems, and changes in cognitive functions. 1

12 The clinical course definitions of MS, devised in consensus among the MS clinical research community, are described in Table 1. 8 Table 1: Clinical Course Definitions of Multiple Sclerosis 8 Disease Category Relapsing-Remitting (RR) MS Primary-Progressive (PP) MS Secondary-Progressive (SP) MS Progressive-Relapsing (PR) MS Definition Clearly defined episodes of acute worsening of neurological function with recovery and stable courses between relapses Gradual, nearly continuous neurologic deterioration from the onset of symptoms with no distinct relapses Gradual neurologic deterioration with or without acute relapses in a patient who previously had relapsing-remitting MS Progressive disease from onset with clear acute relapses, with or without full recovery; periods between relapses characterized by continuing progressive neurologic deterioration It is estimated that 85% of patients with MS present with the relapsing-remitting form and 15% of patients present with primary-progressive MS. 11 Many patients with relapsing-remitting MS eventually enter into secondary-progressive MS. The classification of multiple sclerosis is important, as disease-modifying drugs to date have shown benefit only in relapsing-remitting MS and not primary progressive form. 11 The Search for a Cause The cause of MS is unknown. Researchers believe that a combination of several factors, environmental and genetic and interactions thereof, may be involved. 12, 13 This section provides an overview of some of the key hypotheses about the cause(s) of MS. It is intended to provide an overview and not serve as an exhaustive list. It does not assess the strengths and weaknesses of the hypotheses. Environmental Factors Different environmental factors, both of non-infectious and infectious origin, have been proposed as risk factors for MS. Non-Infectious Population-based environmental factors (rather than common family environmental exposures) during gestation, childhood and even adulthood may play an important role in the development of MS later in life. MS is generally more common in people who live farther from the equator. Decreased sunlight exposure has been linked with a higher risk of MS. Decreased vitamin D production and intake has been the main biological mechanism used to explain the higher risk among those less exposed to the sun. Other factors of interest include severe stress, smoking, exposure to 12, 13, 14 occupational toxins and diet. 2

13 Infectious Epidemiological observations indicate that viral infections could contribute to MS development not only as triggers of disease exacerbations but also as etiological agents long before the disease becomes clinically apparent. Data suggests that, although one MS-causing agent might still be discovered, it may be multiple infections along with non-infectious environmental factors that trigger the development of MS. 15 Some viral agents suspected as triggers of MS include herpes viruses such as varicella-zoster virus (the causative agent of chicken pox), Epstein-Barr virus and Human herpes virus-6, as well as human endogenous retroviruses. 15 In 1966, Leibowitz et al. suggested that the prevalence of MS was correlated with a childhood environment characterized by a high level of sanitation. 16 Similar observations have led to the formulation of the hygiene hypothesis, which proposes that exposure to several infectious agents early in life may be protective against diseases, including MS, with the disease being a response to a later encounter with such agents. 17 As such, a relative lack of evolutionary normal exposure to infectious agents during childhood may predispose susceptible individuals to allergic and autoimmune diseases later in life. 18 However, birth order studies in a large Canadian cohort of MS patients and their siblings did not find any evidence for the hygiene hypothesis. 19 Genetics Although MS is not considered a hereditary disease in the sense that genes alone are causal, research indicates that genetic factors do contribute to an individual s risk of MS. Biologically related family members of affected individuals have a greater risk of disease than the general population, and this risk increased with the amount of genetic sharing (e.g. identical twins >siblings >1/2 siblings >first cousins). 13 Research suggests a parent-of-origin effect in multiple sclerosis susceptibility. 20 Some researchers theorize that a person is born with a genetic predisposition to MS and that exposure to an environmental agent triggers the autoimmune response. 12 Gene gene, gene environment and environment environment interactions are all believed to exist in MS susceptibility. 3

14 Vascular While MS has been well established to be an autoimmune disease in which immune cells mistake myelin for a foreign invader and attack it, 21 the notion of a venous connection to MS has been around for more than a century. 22 A new vascular hypothesis reported by Zamboni and colleagues in 2009, called chronic cerebrospinal venous insufficiency, has raised many questions and prompted research studies regarding the cause of MS, but to date no placebo 23, 24 control studies have been done, and proof of principle studies have been controversial. Diagnosis Early diagnosis and treatment of MS is of key importance, because effective treatment is difficult after the patient has progressed into the later stages of MS. 25 Early optimal treatment studies suggest improved outcomes by delaying the progression of the disease. 26 There are no symptoms, physical findings or laboratory tests that can, by themselves, determine whether a person has MS, and the diagnosis cannot be made in a clinically asymptomatic individual. 27 The diagnosis of MS should be made clinically by a physician specialist with knowledge and experience in neurological conditions. In order to make a diagnosis of MS, the following criteria must be met: 27 There is evidence of damage in at least two separate areas of the central nervous system. There is evidence that the damages occurred at least one month apart. All other possible diagnoses have been ruled out (i.e. differential diagnosis). Comorbidity, the presence of other diseases and health conditions, has been associated with delayed diagnosis and increased disability in MS. 28 The following tests can be employed to support a diagnosis of MS and/or identify levels of impairment and activity limitations that may result: Medical history and neurologic exam a history of past or present symptoms and information about birthplace, family history, places travelled, etc. A variety of neurological tests may also be performed to evaluate mental, emotional and language functions, movement and coordination, balance, vision and the other four senses. Magnetic resonance imaging (MRI) imaging technology for detecting the presence of MS scarring (also called lesions or plaques) within the central nervous system (CNS). The use of a contrast agent containing gadolinium can help differentiate old lesions from new or active lesions. Gadolinium dye does not readily pass through the blood-brain barrier. However, when the blood-brain barrier is damaged by inflammation, the gadolinium leaks out, thus enhancing the lesion. Evoked potential (EP) tests recordings of the nervous system s electrical response to the stimulation of specific sensory pathways (e.g. visual). Damage to myelin results in a slowing of response time. 4

15 Lumbar puncture a spinal tap performed to draw cerebrospinal fluid for analysis. The analysis of the cerebrospinal fluid determines the levels of certain immune system proteins and the presence of oligoclonal bands. These bands, which indicate an immune response within the CNS, are found in the spinal fluid of about 90% to 95% of people with MS. But because they are present in other diseases as well, oligoclonal bands cannot be relied on as positive proof of MS. 27 Blood tests while there is no definitive blood test for MS, blood tests can rule out other conditions that cause symptoms similar to those of MS. In 2006, the National MS Society s International Advisory Committee on Clinical Trials convened the Task Force on Differential Diagnosis in MS that resulted in the development of guidelines for MS differential diagnosis. 29 Before confirming an MS diagnosis, a differential diagnosis must be made to rule out any other condition that may cause symptoms similar to MS, including 27 Infections of the CNS: Lyme disease, syphilis, progressive multifocal leukoencephalopathy, human immunodeficiency virus; Inflammatory disorders of the CNS: systemic lupus erythematosus, Sjögren s syndrome, vasculitis, sarcoidosis and Behçet s disease; Single gene genetic disorders: leukodystrophy (including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), hereditary cerebellar degenerations, hereditary myelopathy and mitochondrial disease; Brain tumors: metastases and lymphoma; Vitamin B12 deficiency; and Other non-ms demyelinating diseases: neuromyelitis optica. Given that no specific diagnostic laboratory test exists for MS, criteria have been developed for the diagnosis of MS. The first widespread set of criteria was established in 1965 by George Schumacher. Dr. Schumacher s focus was clinical trials and the concepts of definite versus probable MS. 30 In 1983, Dr. Charles Poser convened a Workshop on the Diagnosis of Multiple Sclerosis. The resulting article by Poser et al. defined several important concepts (for example, attack, remission, clinical evidence and paraclinical evidence) and five MS categories (clinically definite, laboratory supported definite MS, clinically probable MS, laboratory supported probably MS and no MS). 31 In 2001, Dr. W. Ian McDonald chaired the International Panel on Diagnosis of MS, which brought together international experts to create diagnostic criteria that could be used by practicing physicians and clinical trial researchers. The panel built on the existing criteria while incorporating advances in understanding of MS and newer diagnostic MRI imaging techniques. The McDonald criteria discouraged the use of clinical definite and probable MS in favour of MS, possible MS or not MS. 32 The internationally accepted criteria became known as the McDonald Criteria. The criteria were further refined in 2005 when the panel reconvened and was chaired by Dr. Chris Polman. The panel s goals were to incorporate new evidence, develop refined consensus where evidence was limited and clarify concepts that users thought were confusing or difficult to implement. The revisions addressed dissemination in time using imaging, the incorporation of spinal cord lesions in imaging and the diagnosis of primary progressive MS. 33 5

16 In May 2010, the International Panel on Diagnosis of MS met again to examine requirements for demonstrating dissemination of lesions in space and time and to focus on the application of the McDonald Criteria in pediatric, Asian and Latin American populations. Table 2 presents the resulting 2010 Revised McDonald MS Diagnostic Criteria, which outline what action(s) to take toward making a diagnosis related to varying observations of attacks and lesions. 34 This latest revision allows for MRI evidence of dissemination in time or space and also includes guidelines for the diagnosis of pediatric MS. 34, 35 Table 2: 2010 Revised McDonald MS Diagnostic Criteria Clinical (Attacks) Lesions Additional Criteria to Make Diagnosis 36 2 or More Objective clinical evidence of 2 or more lesions or objective clinical evidence of 1 lesion with reasonable historical evidence of a prior attack 2 or More Objective clinical evidence of 1 lesion 1 Objective clinical evidence of 2 or more lesions 1 Objective clinical evidence of 1 lesion 0 (Progression From Onset) Source National Multiple Sclerosis Society. 36 None Clinical evidence alone will suffice; additional evidence desirable but must be consistent with MS Dissemination in space, demonstrated by: 1 T2 lesion in at least two MS typical CNS regions (periventricular, juxtacortical, infratorial, spinal cord) OR Await further clinical attack implicating a different CNS site Dissemination in time, demonstrated by: Simultaneous asymptomatic contrast-enhancing and nonenhancing lesions at any time OR A new T2 and/or contrast-enhancing lesion(s) on follow-up MRI, irrespective of its timing OR Await a second clinical attack Dissemination in space, demonstrated by: 1 T2 lesion in at least two MS typical CNS regions (periventricular, juxtacortical, infratentorial, spinal cord) OR Await further clinical attack implicating a different CNS site AND Dissemination in time, demonstrated by simultaneous asymptomatic contrast-enhancing and non-enhancing lesions at any time OR A new T2 and/or contrast-enhancing lesion(s) on follow-up MRI, irrespective of its timing OR Await a second clinical attack One year of disease progression (retrospective or prospective) AND at least 2 out of 3 criteria: Dissemination in space in the brain based on 1 T2 lesion in periventricular, juxtacortical or infratentorial regions Dissemination in space in the spinal cord based on 2 T2 lesions OR Positive cerebrospinal fluid 6

17 Treatment There is no known cure for MS. There are a number of treatments and strategies available to help modify the disease course, treat relapses, manage specific symptoms, improve function and safety, and provide emotional support. A multidisciplinary approach is key to improving quality of life. This section is not intended to be an exhaustive list or comprehensive, detailed summary. Pharmacological Medications aimed at treating MS can be divided into several categories: 37 Disease-modifying therapies: Disease-modifying therapies (DMTs) impact the underlying disease. These drugs are also called immunomodulatory therapies and generally work by targeting some aspect of the inflammatory process of MS, with an aim of preventing inflammation which causes relapses. 37 The goal of DMTs is to reduce the frequency and severity of relapses, reduce the accumulation of lesions and, in general, slow the accumulation of disability. 38 Treating exacerbations/relapses: Medications such as steroids help to decrease the severity and duration of MS relapses. A relapse is caused by an area of acute inflammation in the CNS, and steroids work to actively suppress inflammation. Managing symptoms: There are many medications that aim to help ease MS-related symptoms including fatigue, spasticity and pain. Rehabilitation Rehabilitation programs are designed to improve or maintain physical, sensory and mental functions affected by MS. Rehabilitation professionals focus on overall mobility and strength, pain and energy management, while addressing problems with accessibility and mobility, speech and swallowing, and memory and other cognitive functions. 39 Rehabilitation is an important component of comprehensive, quality health care for people with MS, at all stages of the disease. 39 Rehabilitation programs include Physical therapy; Occupational therapy; Therapy for speech and swallowing problems; Cognitive rehabilitation; and Vocational rehabilitation. Vitamin D Vitamin D supplementation, notably early in life, has been proposed to prevent MS. 40 The potential role of vitamin D in modulating MS disease activity is an area of active clinical trials research. The totality of evidence for a protective role of vitamin D in MS has been deemed strong enough by some to warrant recommending vitamin D supplementation to people with MS and to individuals considered at high risk for MS. 41 7

18 Complementary and Alternative Therapies Alternative therapies are those that fall outside the realm of conventional medicine. Complementary therapies, as the name suggests, are therapies used in addition to traditional treatments. Complementary and alternative therapies, such as meditation, yoga, magnetic field therapy, 42, 43 massage, reflexology and acupuncture, have been used to treat MS symptoms. Studies have suggested that exercise, such as aerobic fitness, has a protective effect on parts of the brain that are most affected by multiple sclerosis. 44 Other benefits of exercise include help with symptom management, reducing the risk for depression and the risk of comorbidity, and functional improvements. Experimental Treatments for MS: Chronic Cerebrospinal Venous Insufficiency Treatment Various experimental treatments for MS have been tried for more than a century. Experimental treatments based on small case series need to be rigorously tested before conclusions can be made about the efficacy of the treatment. One of the most recent experimental treatments is for chronic cerebrospinal venous insufficiency (CCSVI). In June 2008, Dr. Paolo Zamboni released preliminary findings proposing an association between MS and a vascular disorder he called CCSVI. 23 Zamboni hypothesized that CCSVI plays a key role in MS by restricting blood flow from the brain, which results in iron deposits that are then targeted by the body s immune response system. Zamboni proposed a treatment, referred to as liberation therapy, in which angioplasty and/or stents are used to liberate or open the restricted veins. Zamboni s CCSVI hypothesis has been met with controversy. 45 Within Canada, there has been much controversy and debate about the effectiveness and safety of CCSVI, as well as 46, 47, 48 continued health care once patients return to Canada after having the procedure abroad. Areas of Research The search to prevent, find a cure for and/or improve the treatment of MS is ongoing. Numerous areas of research related to MS are being explored, including studies on genetics, environmental risk factors, pregnancy, immunology, vitamins, diet, alternative therapies, pain and vaccinations. 43 This section provides an overview of some of the key research efforts and emerging trends. It is not intended to be a comprehensive review of all areas of research nor is it intended to be an exhaustive list. Genetics New techniques and research to identify genes may help answer questions about the role of genes in the development of MS. Candidate gene and whole genome association studies have identified several possible susceptibility loci of relatively small impact in the human genome. The complex human leukocyte antigen genes (HLA) located on chromosome 6 remain the most significant in MS susceptibility in Caucasians, although the HLA effects involve complex interaction within the genotype and with respect to the transmission within families

19 Immunological Several lines of evidence support the hypothesis that autoimmunity the abnormal response of one s immune system against one s own body plays a role in disease development, and that immune abnormalities are important in ongoing MS activity, especially relapses. 53, 54 The precise initiator for the immune response at a cellular level is yet unknown, but researchers have been able to identify immune cells contributing to the attacks and factors influencing the attack, and a range of pharmaceutical treatments have been designed to modulate immune response in one way or another (for example, blocking T-cell movement from the blood into the central nervous system using natalizumab). 55 Ongoing research efforts continue to explore immune system triggers and stimuli, as well as agents implicated in autoimmune disease suppression. For example, a number of researchers are currently exploring the impact of parasitic infection on MS disease progression and activity. 56 Pharmaceutical There is a considerable amount of pharmaceutical research being carried out worldwide aimed at improving the treatment of MS. Gilenya is the first oral therapy designed to reduce relapses and delay the progression of MS available in Canada. All previously marketed drug therapies require injections or infusions. 57 Innovation.org, a project of the Pharmaceutical Research and Manufacturers of America, includes a New Medicines in Development Database, which shows a number of therapies currently in Phase III clinical trials for MS within the United States: Alemtuzumab, Daclizumab, Dimethyl fumarate, Laquinimod (oral therapy), PEG-interferon beta- 1a and Teriflunomide. 58 However it is important to note that these multi-centre studies can span several years and may include Canadian sites, but any therapy marketed in Canada must be approved by Health Canada. Many potential new medicines will fail in clinical trials and never reach the market. Stem Cell Research Stem cells have been used for years to treat blood cancers via transplantation of bone marrow. Scientists have found that the process, known as hematopoietic stem cell transplantation, can be applied to help stop the progression of MS in some patients. 59 There are two kinds of stem cell transplantation: a graft of the patient s own stem cells from the blood or bone marrow that have been purified of immune cells (known as autologous transplantation) and stem cells obtained from a donor s bone marrow or bloodstream (known as allogeneic transplantation). In theory, autologous hematopoietic stem cell transplantation would benefit patients with an autoimmune disease caused by a strong environmental trigger, whereas allogeneic transplantation might be more suitable for treating autoimmune diseases with a strong genetic basis. Ongoing clinical trials in Canada using autologous transplantation to treat MS are in effect testing this hypothesis. 59 9

20 Research is also under way aimed at understanding cell signalling codes to interrupt the pathways that lead to the destruction of the myelin sheath. This will help researchers understand the conditions in which remyelination might occur, and the possible role of drug therapy, gene therapy or stem cell therapy. Scientists working on this aspect of MS say that regenerating lost brain tissue is the next frontier in MS to add repair to what we can already do to fight inflammation. 59 People living with MS have high hopes that the rapid advancements being made in stem cell research may help reduce their symptoms or even cure them of the disease. To help ensure that patients are not put at risk by unproven stem cell procedures, the International Society of Stem Cell Research struck an international task force to develop Guidelines for the Clinical Translation of Stem Cells. 60 The society also advises people to be wary of clinics that offer treatments with stem cells that originate from a part of the body that is different from the part being treated or expensive treatments that have not passed successfully through clinical trials. 61 Vitamin D As previously mentioned, MS is generally more common in people who live farther from the equator. Decreased vitamin D production and intake is now considered one of the possible biological mechanisms used to explain the higher risk among those less exposed to the sun. There is research under way that looks into the possibility of vitamin D as a causative agent as well as the preventive role of vitamin D, not only in reducing the risk of MS but also in the severity and relapse rate for those living with MS. Chronic Cerebrospinal Venous Insufficiency Research into CCSVI is now taking place around the world, with presentations at various meetings such as the European Committee for Treatment and Research in MS (ECTRIMS) in October 2010, the International Society for Neurovascular Disease (ISNVD) in March 2011, the Society of International Radiology in March 2011 and the American Academy of Neurology in April Research is under way in Canada to explore the relationship between CCSVI and MS. In June 2010, the Multiple Sclerosis Society of Canada and the National MS Society (U.S.) committed $2.4 million to seven new research projects focusing on CCSVI and its relationship to MS 63 (see the section Multiple Sclerosis Society of Canada for additional information). In June 2011, the Government of Canada announced a commitment to launching an open and transparent call for applications for Phase I and II clinical trials focused on CCSVI and MS

21 Health Services and Care for People Living With MS in Canada Canadian Network of Multiple Sclerosis Clinics The first Canadian MS clinic was established in 1954 by Dr. Bert Cosgrove and Dr. Roy Swank at the Montreal Neurological Institute (MNI). 65 The MNI MS clinic was followed almost 20 years later with the establishment of the MS clinic at the University of Western Ontario in London, Ontario, in 1972, led by Dr. Donald Paty, 65 as well as with a number of other clinics in the 1970s. It was recognized that a comprehensive clinic model could foster collaboration and education of health care professionals in the care of patients with MS, 30 and in 1998 the Canadian Network of Multiple Sclerosis Clinics was established. (See Appendix A for a list of clinics within the Canadian Network of Multiple Sclerosis Clinics.) The Canadian Network of Multiple Sclerosis Clinics is a national network of academic and community-based clinics established for the advancement of patient services, education, and research in multiple sclerosis. 66 Clinic resources vary, but most offer a wide range of services, delivered by a multidisciplinary health care team, including 66 Expert diagnostic and treatment services; Clinical research, especially related to MS treatment options; and Educational and support programs for people living with MS and their families and caregivers. Other Settings A variety of health care providers outside of the Canadian Network of Multiple Sclerosis Clinics collect information that may be relevant to the monitoring of the evolution and treatment of MS within Canada. Individuals living with MS may receive treatments and therapies from other health providers and complementary and alternative care providers not formally connected with network clinics (for example, family physician, long-term care facility, inpatient acute care, ambulatory care, rehabilitation centre or clinics and neurologists not formally associated with the network). Treatment plans and outcomes may or may not be shared with the network clinics. Overview of Initiatives in Canada There are a number of MS-related initiatives being carried out across Canada. This section provides an overview of the key initiatives as of July 31, The information presented in this section was compiled through research and engagement with key stakeholders. This section is not intended to be an exhaustive list nor is it a comprehensive summary. It should be noted that MS research and activities are funded in many ways and by sources other than those listed here. 11

22 Public Health Agency of Canada The Public Health Agency of Canada (PHAC) is the main Government of Canada agency responsible for public health in Canada. PHAC s role is to promote health; prevent and control chronic diseases and injuries; prevent and control infectious diseases; prepare for and respond to public health emergencies; serve as a central point for sharing Canada s expertise with the rest of the world; apply international research and development to Canada s public health programs; and strengthen intergovernmental collaboration on public health and facilitate national approaches to public health policy and planning. 67 The Canadian Multiple Sclerosis Monitoring System To help people make more informed choices about care, it is important that we understand the disease, its progression and the use of treatments. As such, there is a need for high-quality data on MS in Canada to provide information on risk factors, greater insight to patients, providers and policy-makers into the appropriate application of interventions, and quality and costs of care. In March 2011, the Government of Canada announced that it would fund $2 million for the development of a Canadian Multiple Sclerosis Monitoring System. 68 The Canadian MS Monitoring System will be led by CIHI, in collaboration with the provinces and territories, the Canadian Network of Multiple Sclerosis Clinics and the Multiple Sclerosis Society of Canada. It will measure and monitor the evolution and treatment of MS in Canada with the goal of providing information to inform decision-making in order to improve outcomes for people living with MS and their caregivers. It is intended that the Canadian MS Monitoring System, when integrated with the other key initiatives in Canada, will provide a comprehensive picture of the evolution and treatment of MS in Canada. The Canadian MS Monitoring System is a multi-phase initiative. The first phase will collect clinical information from the Canadian Network of MS Clinics. Subsequent phases will look at opportunities to collect information from other data sources outside of the network. CIHI will partner with the Canadian Network of Multiple Sclerosis Clinics to collect information from its patients on a voluntary basis. To inform the development of this initiative, it is important to learn more about the current landscape of the Canadian Network of MS Clinics. Due to the voluntary nature of the Canadian MS Monitoring System, gauging the readiness of the clinics to participate in terms of level of interest, capacity and the potential support that may be required will be key. The primary goal of the Canadian MS Monitoring System is to record, measure and monitor the evolution and treatment of MS in Canada to better understand care patterns and patient outcomes and to improve the quality of life of Canadians living with MS. This new system will significantly increase understanding of MS and ultimately improve patient care and quality of life by Measuring disease patterns across Canada; Identifying variation in use of treatment; and Monitoring long-term patient outcomes. 12

23 The development and implementation of a well-integrated, voluntary, national monitoring system for MS is a multi-year initiative. The monitoring system will be developed in CIHI will work in close collaboration with clinical and technical experts from across Canada, the Canadian Network of Multiple Sclerosis Clinics, the Multiple Sclerosis Society of Canada and provincial and territorial governments to develop and design the system. CIHI will work closely with subject matter experts to identify the priority information that should be collected and submitted to the MS monitoring system and how frequently data should be collected. CIHI will partner with the Canadian Network of Multiple Sclerosis Clinics to collect information from its patients on a voluntary basis. Data collection protocols will be developed by CIHI to ensure standardized data collection across all participating MS clinics. CIHI will also work closely with the Canadian Network of Multiple Sclerosis Clinics to make sure that the data collection tools can be implemented uniformly across the network. The approach is to develop a system that captures data at point of care, avoids duplication of efforts and minimizes burden on patients and clinicians. In addition to funding the development of the Canadian MS Monitoring System, PHAC has provided funding for a number of MS-related initiatives already under way, which are outlined below. Canadian Chronic Disease Surveillance System The Canadian Chronic Disease Surveillance Systems (CCDSS) is a collaborative initiative supported by PHAC that uses administrative data to report on the incidence and prevalence of chronic diseases across Canada. The CCDSS was formerly known as the National Diabetes Surveillance System (NDSS), which released its first report on diabetes in In 2009, the surveillance system was expanded to include hypertension, with the first report released in The feasibility of expanding the CCDSS to include other chronic neurological disease conditions, including MS, is currently being explored. The CCDSS operates as a network of provincial and territorial surveillance systems. In each province and territory, the health insurance registry database is linked to the physician billing and hospitalization databases to provide data for surveillance at the provincial/territorial level. The micro-data is held and maintained within the respective province/territory with aggregate data being made available to PHAC for reporting at the national level. Based on current data sources described above, the CCDSS does not capture detailed clinical information, risk factor information or information on determinants of health. Its primary purpose is to provide regular reports on the prevalence and incidence of specific chronic diseases. 13

24 National Population Health Study of Neurological Conditions The National Population Health Study of Neurological Conditions (NPHSNC) is a four-year initiative announced by the federal Minister of Health on June 5, The NPHSNC is administered through PHAC s Enhanced Surveillance for Chronic Disease Program and aims to provide key information to improve current knowledge of the prevalence, risk factors, use of health services, economic cost, and impact of neurological disease currently and projected over the next 20 years. 71 At the conclusion of the four-year study, a comprehensive report will be produced with key findings to be communicated at a conference to take place in While not an ongoing initiative, this study will provide a comprehensive picture of MS at this point in time. PHAC is working with the Neurological Health Charities Canada, Health Canada, the Canadian Institutes of Health Research and Expert Advisory Groups on the National Population Health Study of Neurological Conditions. As part of the study, a suite of neurological projects were started in 2010 and will end in (See Appendix B for an overview of the MS-related projects.) The following survey-based work is also under way: The addition of a neurological conditions module to Statistics Canada s Canadian Community Health Survey (CCHS) This module collects information on neurological conditions in Canada, including MS. The CCHS is a cross-sectional survey that collects information related to health status, health care utilization and health determinants for the Canadian population. 72 The target population of the CCHS is all Canadians age 12 and older. Funding amounts for this project were not available at the time this report was written. 73 Please refer to the following section (on Statistics Canada) for additional information about the CCHS. The Survey on Living with Neurological Conditions in Canada (SLNCC). The SLNCC is a follow-up survey of a sub-sample of individuals identified as having a neurological condition in Statistics Canada s 2010 CCHS. The objective of the SLNCC is to learn more about the impact of neurological conditions on individuals and caregivers. The SLNCC questionnaire is being developed with expert advice from Statistics Canada and will be carried out via telephone interviews in Sample size and response rate will have a significant impact on the ability to conduct in-depth analysis on people living with MS, as well as the limitations of that analysis. The data from the SLNCC is expected to be available in fall Statistics Canada will retain the master file and maintain the database, while PHAC will receive a share file. The SLNCC is currently planned as a one-off survey. Funding amounts for this project were not available at the time this report was written. 73 The Survey of Living with Neurological Conditions in Institutions. The objective of this survey is to determine the prevalence of neurological conditions, including multiple sclerosis, in long-term care facilities (meaning those conditions which are not captured in the abovementioned Survey on Living with Neurological Conditions in Canada). Like the SLNCC, sample size and response rate will have a significant impact on the ability to conduct indepth analysis on people living with MS, as well as the limitations of the analysis. This project is planned as a one-off survey and is currently in the feasibility stage. Funding amounts for this project were not available at the time this report was written

25 Statistics Canada Statistics Canada is an agency within the Government of Canada with the mandate to collect, compile, analyse, abstract and publish statistical information relating to the commercial, industrial, financial, social, economic and general activities and conditions of the people of Canada. 74 Statistics Canada has the following MS-related initiatives under way: Canadian Community Health Survey In 1991, the National Task Force on Health Information identified a number of issues with the health information system. To respond to these issues, the Canadian Institute for Health Information, Statistics Canada and Health Canada joined forces to create a Health Information Roadmap. From this mandate, the Canadian Community Health Survey (CCHS) was conceived. 72 The CCHS is a cross-sectional survey that collects information related to health status, health care utilization and health determinants for the Canadian population. A key objective of the CCHS is to support health surveillance programs by providing health data at the national, provincial and intra-provincial levels. It also serves as a flexible survey instrument that includes a rapid response option to address emerging issues related to the health of the population. 72 The target population of the CCHS is all Canadians age 12 and older. The main use of the CCHS data is for health surveillance and population health research. Commencing in , a neurological conditions module has been added to the CCHS. This module collects information on 14 priority neurological conditions in Canada, including MS. 75 Data collection is scheduled to occur between September 2011 and March Microsimulation Models The Health Analysis Division of Statistics Canada has a focus on policy-relevant health-related computer simulation models. These models are tools used to evaluate the impact of health interventions and policies at the population level. They use data from Statistics Canada s data holdings to represent the Canadian population with attributes such as risk factor exposures, health histories and demographic characteristics typical of Canadians. The models simulate histories for individual persons in continuous time and use this information to create aggregate results for the total population. The Population Health Model (POHEM) is a microsimulation model of diseases and risk factors in which the basic unit of analysis is the individual person. POHEM combines data from a wide range of sources, including nationally representative cross-sectional and longitudinal surveys, registries, hospitalization databases, vital statistics and census. New models are under development with the Public Health Agency of Canada to project the future health and economic burden of key neurological diseases. The first phase will be a model of Canadians with neurological diseases that will project the incidence and prevalence of key neurological conditions, the impact on mortality, life expectancy, disability-adjusted life years and health-adjusted life expectancy (HALE) and the direct costs of treatment and indirect costs (lost wages and tax revenue)