Abstract: 256
Type: Oral
The fundamentals of well-planned, organized, randomized, placebo-controlled, multicenter clinical trials as attempts to develop evidence based therapeutics for multiple sclerosis (MS) have their origins midway through the last century. Consistent with trials throughout the landscape of intervention in human disease, they rest on attempts to condense the insights and wisdom of clinical judgement into definitions of the disease, categorization of subtypes and severity, and elements of anticipated outcomes; all intended to reduce heterogeneity among study participants and reduce the information collected to meaningful categorical and continuous measures subject to ever refined statistical analyses and inferences of benefit or harm. The global think tank of the early 1980"s that evolved into the International Advisory Committee on Clinical Trials of New Drugs in MS has iteratively and successfully spurred many refinements. Generally, the discovery progress in trials is accelerated where biomarkers associated with clinical outcomes exist to support, if not extend or replace, less precise clinical outcome measures. Magnetic resonance imaging (MRI) was promptly embraced as a portal to the pathology of MS, it"s potential as a critical MS biomarker immediately recognized, and MRI was rapidly attached to multicenter clinical trials by 1984. Technical advances in MRI have been rapid as have been advances in our understanding of MS pathogenesis, clinical trial design and more optimal integration of MRI to MS diagnosis and our pursuit of improved therapeutics over the ensuing decades. As a biomarker, quantitative serial MRI is now indispensable for developing disease modifying drugs in relapsing forms of MS; its best use in progressive phase disease trials remains more enigmatic, but no more so than that of our current clinical endpoints. This overview will consider where we have been, where we are, promising newer image acquisition and analytic approaches, and some of the challenges that lay ahead.
Disclosure: Over the past year, I served on advisory boards, data monitoring or steering committees, held consulting agreements, or received speaker honoraria from the following commercial entities: AbbVie, AcademicCME, Alkermes, Antisense Therapeutics, Bayer HealthCare, Forward Pharma A/S, medDay, Mapi Scientific, Novartis, Roche/Genentech, Sanofi Genzyme, Takeda, Teva Pharmaceuticals, WebMD.
Abstract: 256
Type: Oral
The fundamentals of well-planned, organized, randomized, placebo-controlled, multicenter clinical trials as attempts to develop evidence based therapeutics for multiple sclerosis (MS) have their origins midway through the last century. Consistent with trials throughout the landscape of intervention in human disease, they rest on attempts to condense the insights and wisdom of clinical judgement into definitions of the disease, categorization of subtypes and severity, and elements of anticipated outcomes; all intended to reduce heterogeneity among study participants and reduce the information collected to meaningful categorical and continuous measures subject to ever refined statistical analyses and inferences of benefit or harm. The global think tank of the early 1980"s that evolved into the International Advisory Committee on Clinical Trials of New Drugs in MS has iteratively and successfully spurred many refinements. Generally, the discovery progress in trials is accelerated where biomarkers associated with clinical outcomes exist to support, if not extend or replace, less precise clinical outcome measures. Magnetic resonance imaging (MRI) was promptly embraced as a portal to the pathology of MS, it"s potential as a critical MS biomarker immediately recognized, and MRI was rapidly attached to multicenter clinical trials by 1984. Technical advances in MRI have been rapid as have been advances in our understanding of MS pathogenesis, clinical trial design and more optimal integration of MRI to MS diagnosis and our pursuit of improved therapeutics over the ensuing decades. As a biomarker, quantitative serial MRI is now indispensable for developing disease modifying drugs in relapsing forms of MS; its best use in progressive phase disease trials remains more enigmatic, but no more so than that of our current clinical endpoints. This overview will consider where we have been, where we are, promising newer image acquisition and analytic approaches, and some of the challenges that lay ahead.
Disclosure: Over the past year, I served on advisory boards, data monitoring or steering committees, held consulting agreements, or received speaker honoraria from the following commercial entities: AbbVie, AcademicCME, Alkermes, Antisense Therapeutics, Bayer HealthCare, Forward Pharma A/S, medDay, Mapi Scientific, Novartis, Roche/Genentech, Sanofi Genzyme, Takeda, Teva Pharmaceuticals, WebMD.