@article {dong_further_2014,
	title = {Further investigation of safety monitoring guidelines based on magnetic resonance imaging lesion activity in multiple sclerosis clinical trials},
	journal = {Multiple Sclerosis Journal},
	volume = {21},
	year = {2015},
	pages = {101-104},
	abstract = {<p>We assess two modified guidelines for monitoring patient safety in multiple sclerosis (MS) trials. These guidelines flag patients with an increase in contrast enhancing lesion (CEL) count above a threshold over the CEL level 1{\textendash}2 months earlier. We compare the new guidelines to the original guideline where the threshold is set according to the baseline by applying the guidelines to two previous studies. The odds ratios of a subsequent clinical relapse associated with meeting the CEL threshold based on the modified guidelines are similar to those based on the original guideline. There is a need for patient and cohort specific monitoring procedures.</p>
},
	keywords = {Clinical trials methodology, contrast-enhancing lesions, magnetic resonance imaging, multiple sclerosis, patient safety},
	doi = {10.1177/1352458514533846},
	url = {http://msj.sagepub.com/content/early/2014/05/20/1352458514533846},
	author = {Dong, J and Zhao, Y and Petkau, A.John and Li, DKB and Riddehough, A and Traboulsee, A}
}
@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}
}
