The global aim of our studies is to optimize clinical trial methodology in the field of Traumatic Brain Injury (TBI) to maximize the chance of demonstrating benefit of new therapies. The proposal concerns a combined methodological and clinically orientated research project involving multidisciplinary expertise from the field of biostatistics, epidemiology and clinical neurotraumatology. It is organized as an international collaboration and built on the sharing of extensive TBI databases. We will create the IMPACT* database as a unique research resource, including data from a total of over 40,000 patients from five multi-center surveys and eleven clinical trials. This database will be used as culture medium for improving trial design.
Specific aim 1 will address the benefits of covariate adjustment and innovative statistical approaches which better exploit the ordinal nature of TBI outcome measures.
Specific aim 2 will use advanced statistical techniques for dealing with center effects and variation in patient management. We anticipate that results will also provide novel evidence in support of treatment recommendations in TBI, an area where to date evidence is woefully inadequate.
Specific aim 3 will provide recommendations for better standardization and increased sensitivity of outcome measures.
Specific aim 4 will address the relative merits of the large, simple """"""""mega trial"""""""" compared to a conventional focused phase III trial and will greatly assist in choosing the best design for future trials. Our results will contribute to the broader NIH plans for reshaping clinical research infrastructure and will facilitate the efficient execution of clinical research in the field of TBI. Relevance: Traumatic Brain Injury constitutes a major health and socioeconomic problem throughout the world. Pre- clinical work has generated many promising therapies, but clinical studies have failed to show convincing evidence of efficacy in the overall TBI population. Various agents may wrongly have been discarded due to insensitive clinical trial methodology.
We aim to improve trial methodology to give new therapies a better chance in the future, and thus to contribute to improved standards of care for future patients. IMPACT: International Mission on Prognosis and Analysis of Clinical Trials in TBI.
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