RT Journal Article
SR Electronic
T1 E03 Can The Distribution Of Caudate Atrophy Rates Seen Over Short Time Intervals Be Predicted From Changes Over Longer Intervals?
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP A36
OP A36
DO 10.1136/jnnp-2014-309032.106
VO 85
IS Suppl 1
A1 RE Farmer
A1 A Mulick Cassidy
A1 NZ Hobbs
A1 R Scahill
A1 EM Rees
A1 S Haider
A1 RAC Roos
A1 A Durr
A1 BR Leavitt
A1 GB Landwehrmeyer
A1 SJ Tabrizi
A1 C Frost
YR 2014
UL http://jnnp.bmj.com/content/85/Suppl_1/A36.2.abstract
AB Background TRACK-HD and PADDINGTON are both longitudinal studies whose aims included assessing the potential of various biomarkers as outcomes for clinical trials of new Huntington’s disease (HD) therapies. One such biomarker is caudate atrophy. This potential is dependent upon the distribution of change in patients, with the distribution of change in healthy controls being indicative of what a successful treatment might achieve. Aims Appropriate statistical models may be fitted to repeated measures to predict the distribution of changes that would be seen over time intervals not utilised in the index study. TRACK-HD involved yearly follow up over 36 months whilst PADDINGTON assessed changes over shorter intervals. Our aim was to compare the distributions of observed 6, 9 and 15 month caudate atrophy seen in PADDINGTON with that predicted from TRACK-HD. Methods/techniques Linear mixed models were fitted separately to data from the early-HD and control subjects in TRACK-HD to predict the mean and standard deviation of caudate atrophy rates over 6, 9 and 15 months. These predictions (and their 95% confidence intervals) were compared with the observed means and standard deviations from PADDINGTON and their confidence intervals. Predicted and observed effect sizes were also compared. Results/outcome As assessed using confidence intervals, predictions from TRACK-HD and observed results in PADDINGTON were consistent with one another. Confidence intervals for predictions made from TRACK-HD were narrower than those for the analogous observed estimates from PADDINGTON. The predictions did not exhibit implausible patterns of behaviour over time that sometimes occurred with the observed PADDINGTON data, which were likely the result of chance variability. Conclusions Appropriate statistical models,when used with repeated measures of caudate atrophy, have great utility in predicting the distribution of atrophy rates time over intervals shorter than those used in the index study.