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Biomedical subjects

Douglas S Goodin

Publications and source records attributed to Douglas S Goodin.

10 recordsLinked to original sources
PubMed2006

Magnetic resonance imaging as a surrogate outcome measure of disability in multiple sclerosis: have we been overly harsh in our assessment?

OBJECTIVE: The validity of magnetic resonance imaging (MRI) as a surrogate outcome measure in multiple sclerosis (MS) clinical trials has been greeted skeptically both by the US Food and Drug Administration and by clinical researchers because the correlation between current MRI measures and clinical disability, although significant, has generally been low. Thus, the reported correlations have varied between rho = 0.09 and rho = 0.60, and have often been at the lower end of this range. Nevertheless, it still appears possible that this apparently poor correlation is due not to any deficiency either with our current MRI measures or with our disability scale, but rather to the intrinsic variability in the clinical expression of MS plaques in different anatomical locations. METHODS: This article explores this possibility through the development of a general mathematical model for the relation between MRI changes and clinical disability in patients with MS. RESULTS: Under the conditions of this general model, the maximum expected correlation between clinical disability and MRI will typically be quite low (eg, rho = 0.2-0.3), even when it is assumed that the MRI changes are the sole determinant of disability and, furthermore, that the scale used to measure disability is ideal. INTERPRETATION: These observations, together with the significant relations already reported between MRI and disability (with observed correlations in the range of 0.2-0.6), actually suggest that our available clinical and MRI measures are considerably better than is currently believed and, in fact, that the MRI may be a valid surrogate marker in the assessment of treatment efficacy in MS.

Disability Evaluation↗
PubMed2004

Disease-modifying therapy in MS: a critical review of the literature. Part I: Analysis of clinical trial errors.

Several types of errors are commonly made during the conduct, analysis, and interpretation of clinical trials in multiple sclerosis (MS). These include statistical errors of overestimating the significance of trial results, particularly when multiple endpoints are evaluated. They also include errors arising from the use of inappropriate covariate analyses, meta-analyses, and post hoc subgroup analyses. Interpretation of trial results can also be confounded by regression to the mean, by post hoc data re-analysis, and by the use of a non-concurrent control population. As these kinds of errors continue to plague the medical literature, it has become important for physicians to be able to assess critically the reports of clinical trial results. In turn, this has made it necessary for physicians to become familiar with the rudiments of the fields of statistics, epidemiology, and trial design. It is the purpose of this manuscript, therefore, to provide an overview of these principles through a detailed analysis of these kinds of clinical trial errors, together with examples that have actually occurred in the recently published MS literature.

Bias↗
PubMed2004

Disease-modifying therapy in MS: a critical review of the literature. Part II: Assessing efficacy and dose-response.

The use of so-called evidence-based medicine represents a structured way in which to critically assess the medical literature with the goal of defining the value of different therapeutic interventions and, ultimately, improving both physician decision-making and patient outcome. This is not a consensus-based process of the type that has often been employed previously in the development of treatment guidelines. Rather, these assessments involve a series of structured steps. Initially, the specific clinical questions to be answered are defined and the evidence is assembled following a structured literature search. Then, the individual studies are classified as to the quality of the evidence provided, and, finally, using a set of pre-specified rules, this evidence is translated into specific recommendations and conclusions. In this manner, evidence-based medicine can be a very powerful tool for practicing physicians and, consequently, it is important that they become familiar with the fundamentals of this analytical approach. It is the purpose of this manuscript, therefore, to provide an overview of this process using examples from two recently completed assessments on disease-modifying therapies in multiple sclerosis.

Dose-Response Relationship, Drug↗
PubMed2003

Stimulus recognition and its relationship to the cerebral event-related potential.

BACKGROUND: The relationship between the event-related cerebral potential (ERP) and perceptual awareness by the subject is poorly understood. The authors manipulated the process of stimulus recognition to examine the effect of changes in a subject's awareness on different components of the ERP and on behavioral (motor) responses. METHODS: Ten subjects listened to a series of 400 tone pips, one of which (frequent tone) was slightly louder than the other (rare tone; 14% of trials). Stimuli were presented in blocks of 10 tones and, following each block, subjects were asked how many rare tones they had detected and if they were aware of any errors that they had made during that block. Cerebral and motor responses were recorded by surface electrodes. RESULTS: When subjects were aware of having responded erroneously to either the rare or frequent tone, their response times were shorter than for correct responses to that tone. When subjects were unaware of such errors, however, the response times were delayed compared to correct responses and to error responses of which the subject was aware. When the subject made an error by responding to the rare tone as if it were frequent and was aware of the error, the N2 and P3 latencies were delayed. By contrast, when subjects were unaware of such errors, no N2 or P3 components were present. Similar findings were noted when subjects responded to a frequent tone as if it were rare. CONCLUSIONS: These results suggest that the N2 and P3 components of the ERP reflect the awareness of the subject that an unexpected event has occurred, regardless of whether it is an unexpected stimulus or an unexpectedly erroneous response to that stimulus. The recording of ERP may provide a means of measuring perceptual awareness in other contexts.

Acoustic Stimulation↗
PubMed2002

Neuromyelitis optica.

Whether neuromyelitis optica (NMO), the co-occurrence of myelitis and optic neuritis, is a variant of multiple sclerosis (MS) or a unique disease is controversial. Distinct neuropathological features and a fulminant clinical course argue in favor of NMO as a distinct disease. However, the combination of neurological impairments of myelitis and optic neuritis occurs in patients with several inflammatory disorders, including multiple sclerosis and collagen vascular diseases. NMO is also associated with certain infectious diseases. The fact that the NMO phenotype occurs in a variety of disease states suggests that NMO does not represent a specific clinical entity. To better understand NMO and its associations with recognized diseases, a systematic review of the literature using MEDLINE was conducted. The history of NMO, its nosology, associations with other diseases, and current concepts of its pathogenesis and treatment is reviewed in this article.

Adult↗