TY - JOUR
T1 - Outcome markers for clinical trials in cerebral amyloid angiopathy
AU - Greenberg, Steven M.
AU - Salman, Rustam Al Shahi
AU - Biessels, Geert Jan
AU - van Buchem, Mark
AU - Cordonnier, Charlotte
AU - Lee, Jin Moo
AU - Montaner, Joan
AU - Schneider, Julie A.
AU - Smith, Eric E.
AU - Vernooij, Meike
AU - Werring, David J.
N1 - Funding Information:
We thank Susanne van Veluw, M Edip Gurol and Panos Fotiadis for assistance with figures. SMG is funded by the National Institutes of Health ( R01 AG26484, R01 NS070834 ). RA-SS is funded by a Medical Research Council senior clinical fellowship. GJB is funded by the Netherlands Organization for Health Research and Development (ZonMw Vidi grant 91711384 ) and the Netherlands Heart Foundation ( grant 2010T073 ). J-ML is funded by the National Institutes of Health ( R01 NS067905 ). MV is funded by an Erasmus MC Clinical Fellowship. DJW's centre receives funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme.
PY - 2014/4
Y1 - 2014/4
N2 - Efforts are underway for early-phase trials of candidate treatments for cerebral amyloid angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for cerebral amyloid angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for cerebral amyloid angiopathy trials are probably applicable also to other small-vessel brain diseases.
AB - Efforts are underway for early-phase trials of candidate treatments for cerebral amyloid angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for cerebral amyloid angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for cerebral amyloid angiopathy trials are probably applicable also to other small-vessel brain diseases.
UR - http://www.scopus.com/inward/record.url?scp=84896084145&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(14)70003-1
DO - 10.1016/S1474-4422(14)70003-1
M3 - Review article
C2 - 24581702
AN - SCOPUS:84896084145
VL - 13
SP - 419
EP - 428
JO - The Lancet Neurology
JF - The Lancet Neurology
SN - 1474-4422
IS - 4
ER -