@article {zhao_personalized_2015,
	title = {Personalized activity index, a new safety monitoring tool for multiple sclerosis clinical trials},
	journal = {Multiple Sclerosis Journal {\textendash} Experimental, Translational and Clinical},
	volume = {1},
	year = {2015},
	pages = {1-15},
	abstract = {<p>Background An abnormal increase of contrast-enhancing lesion (CEL) counts on frequent MRIs is interpreted as a signal of potential worsening in multiple sclerosis (MS) clinical trials. We demonstrate the utility of the MR personalized activity index (MR-pax) to identify such increases. Methods We analyzed a previous Phase II study in relapsing patients (n = 167) with MRIs at screening, baseline and months 1{\textendash}6. We performed five consecutive reviews at 90-day intervals. At each review, we evaluate the MR-pax for each patient and also identify those who meet the rule-of-five (an ad-hoc guideline currently in use). To evaluate its clinical relevance, we assess the relation between having a small MR-pax (<=0.05; indicating an unexpected CEL increase) and relapse status in the 12 weeks post-review. Results Of the 399 patient reviews, 35 cases met the rule-of-five; 35 had an MR-pax <= 0.05; 18 met both criteria. The proportions experiencing clinical relapse are 63\% among those meeting the rule-of-five, 61\% among those with MR-pax <=0.05, and 83\% for those meeting both criteria, more than double the rate of those meeting neither criterion (40\%). Conclusion A guideline combining this new personalized index and the existing threshold-based criterion is able to better identify patients with a higher risk of experiencing relapses.</p>
},
	keywords = {contrast-enhancing lesions, MRI, multiple sclerosis, safety monitoring in clinical trials},
	doi = {10.1177/2055217315577829},
	url = {http://mso.sagepub.com/content/1/2055217315577829},
	author = {Zhao, Y and Kondo, Y and Traboulsee, A and Li, DKB and Riddehough, A and Petkau, A.John}
}
