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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS042691-04A1
Application #
7194924
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Gilbert, Peter R
Project Start
2002-01-01
Project End
2007-09-16
Budget Start
2007-04-16
Budget End
2007-09-16
Support Year
4
Fiscal Year
2007
Total Cost
$416,857
Indirect Cost
Name
Erasmus University of Rotterdam
Department
Type
DUNS #
410450258
City
Rotterdam
State
Country
Netherlands
Zip Code
Maas, Andrew I R; Murray, Gordon D; Roozenbeek, Bob et al. (2013) Advancing care for traumatic brain injury: findings from the IMPACT studies and perspectives on future research. Lancet Neurol 12:1200-10
Roozenbeek, Bob; Maas, Andrew I R; Menon, David K (2013) Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol 9:231-6
van Leeuwen, Nikki; Lingsma, Hester F; Perel, Pablo et al. (2012) Prognostic value of major extracranial injury in traumatic brain injury: an individual patient data meta-analysis in 39,274 patients. Neurosurgery 70:811-8; discussion 818
Adelson, P David; Pineda, Jose; Bell, Michael J et al. (2012) Common data elements for pediatric traumatic brain injury: recommendations from the working group on demographics and clinical assessment. J Neurotrauma 29:639-53
Weir, James; Steyerberg, Ewout W; Butcher, Isabella et al. (2012) Does the extended Glasgow Outcome Scale add value to the conventional Glasgow Outcome Scale? J Neurotrauma 29:53-8
Roozenbeek, Bob; Lingsma, Hester F; Lecky, Fiona E et al. (2012) Prediction of outcome after moderate and severe traumatic brain injury: external validation of the International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic mod Crit Care Med 40:1609-17
Roozenbeek, Bob; Lingsma, Hester F; Maas, Andrew Ir (2012) New considerations in the design of clinical trials for traumatic brain injury. Clin Investig (Lond) 2:153-162
Turner, Elizabeth L; Perel, Pablo; Clayton, Tim et al. (2012) Covariate adjustment increased power in randomized controlled trials: an example in traumatic brain injury. J Clin Epidemiol 65:474-81
Van Calster, Ben; Van Belle, Vanya; Vergouwe, Yvonne et al. (2012) Discrimination ability of prediction models for ordinal outcomes: relationships between existing measures and a new measure. Biom J 54:674-85
Roozenbeek, Bob; Lingsma, Hester F; Perel, Pablo et al. (2011) The added value of ordinal analysis in clinical trials: an example in traumatic brain injury. Crit Care 15:R127

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