Reader Comments

Post a new comment on this article

Referee comments: Referee 2

Posted by PLOS_ONE_Group on 10 Apr 2008 at 16:22 GMT

Referee 2's review:

N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.

Paul and colleagues report a trial of oral high-dose atorvastatin for treatment of active relapsing-remitting MS. The trial is generally well-designed and reported given the limitations of an open-label study.

How were participants for this study identified? Did they have clinically active disease at the time of the screening MRI? Indicate reasons for screen failure (n=39).

Please clarify the target sample size based upon the stated power calculation.

I strongly suggest that the authors delete the term "intention-to-treat" from the manuscript. This term denotes very specific approaches to statistical comparisons in controlled studies, which this is not. Simply describe that patients who did not complete 6 months of therapy were excluded - the authors have appropriately described the 5 patients who did not.

The data should be consistently reported using the 2-sided test results. There is no justification provided a priori for reporting a 1-sided test result and the study was based on a 2-sided power calculation; instead, indicate the trend and that the sample is not large enough to demonstrate statistical significance. Also revise the discussion/conclusions/abstract accordingly.

The authors correctly point out the limitation of regression to the mean. In their discussion, they mention the concern of utilizing placebo-controlled approaches for MS studies, but conclude by declaring that such studies are now warranted. Is it not a greater ethical challenge to propose a placebo-controlled study with these data in hand? Consider revising this inconsistency.