Hi Megc,
The first issue is related, but not exactly the same point as raised by Bhatt and me. Related enough so that the Bhatt paper can be considered in the appeal? Well, that is being debated by lawyers who have different opinions. My opinion is that yes, it is related enough, but I am not a lawyer.
To be more clear:
Statement 1 from post trial finding: "the person of ordinary skill in the art would have attributed the absence of a statistically significant increase in the EPA arm to (1) the study’s small sample size (19 patients in the EPA group and 17 patients in the DHA group) ..."
How is this statement related to the result found by Bhatt and myself?
A POSA would have looked at the study and said to himself, "hmm, Mori did not directly compare EPA to DHA. If I want to claim DHA raises LDL levels more than EPA (a fact I would want to know if I am going to bother to purify EPA) then I better do the direct comparison". If the POSA did the direct comparison, and, hypothetically, found that DHA does raise LDL more than EPA then he would say, "OK, I can make the claim, sample size be damned, because the statistical test accounts for sample size". So in this instance sample size is irrelevant.
On the other hand, if he did the direct test and found there was not a statistically significant difference between the two group (which is what both Bhatt and I did and found this was indeed the case), he might still wonder why, if there is no statistical difference between the EPA and DHA groups, why did the DHA group show a statistically significant difference from placebo, whereas EPA group did not? Well to explain that fact you would invoke sample size -- either the direct comparison was not sufficiently powered or the EPA to placebo comparison was not sufficiently powered.
Now the second statement is a different issue entirely:
>(2) the difference in the baseline TG levels of the two groups, with the EPA group having a mean TG level 11% lower than the DHA group (2.01 mmol/L or 178 mg/dL for the EPA group versus 2.25 mmol/L or 199 mg/dL for the DHA group).
It is known that the expected change in LDL levels upon DHA treatment is correlated with the baseline TG levels in the patient (higher TGs = bigger increase in LDL upon DHA treatment). This has two implications, both of which were pointed out by Amarin's lawyers. First, the populations analyzed in Mori have much lower triglyceride levels on average than what is specified in the MARINE indication. So they argue Mori is irrelevant on those grounds. I tend to agree. The second implication is what is stated above -- that because the DHA and EPA groups have different mean TGs, any between group difference in change in LDL could be accounted for that. (one caveat is that the linear regression model that Mori used was not clearly specified, so perhaps this was accounted for in their model?).
I think Amarin's lawyers argued -- "We concede Mori shows something but it should be ignored based on small sample size and the TG level issue". I agree with this argument. But a stronger argument that can be made now is: "With respect to the question of whether EPA and DHA treatments have different effects on LDL levels, Mori teaches nothing". The TG argument is now not needed to disqualify what Mori teaches, because Mori teaches nothing w.r.t. that issue.
