As a precaution against the risk of Type I errors, the statistical plan prioritised testing of the primary hypotheses of interest (differences at baseline and time of maximum clinical effect i.e. week 6).
The clinical score of the polyI C group showed significant increase compared with the saline group and the LPS group from 15 days after pristane injection, and maximum clinical score of the polyI C group consistently had a significant difference compared with other groups.
No difference in the day of onset of clinical EAE nor the maximum clinical score was observed between Tie-2 tTA//TRE-claudin-1 C57BL/6 mice, and single transgenic or wild-type littermates (Fig. 3 and data not shown).
This difference was present in rats with the same onset of disease and maximum clinical severity, likely reflecting that DA.PVG-Eae23 rats recovered from the first bout of disease to a larger extent than DA rats and had milder disease in the chronic phase of EAE (Figure 3).
Two out of 10 monkeys who received 15 times the maximum clinical dose of E26, the next generation drug, died.
The monkeys that developed low platelet levels, a condition that can lead to uncontrolled bleeding, received 3 to 27 times the maximum clinical dose.
Whether statistical difference also translates to clinical difference remains to be seen.
A difference of 1 day was considered to be the maximum clinically acceptable difference.
Adjusting for clinical differences among patients did not change the findings.
The rationale for clinical differences is compartment saturation.
