Amarin Corp Plc (AMRN)

[HDGabor]

K-

If you would like to continue a meaningful discussion, talk with your wife first (before post) ...

Re what would I like to suggest / say etc

"Early stopping of a clinical trial for evidence of benefit has been widely debated in the medical literature.", but let me guess (since you did not address the question):

- definitely not about pt yrs, since the citation does not deal with it ...
- EMPHASIS-HF / survival concern: we do not know what is role of survival in the analysis, but we know that ALL (inc. secondary) endpoints should be ...
- HOPE trial / PE and SEs: "the primary composite end point was positive early in the trial, but the DMC waited to recommend stopping the study until all components of the primary were positive." - again, ALL (inc. secondary) endpoints should be ...
- ASCOT-BPLA: "he DMC recommended stopping the trial early after interim analyses indicated that patients randomly assigned to the amlodipine-based regimen had a lower incidence of fatal and nonfatal stroke (230 versus 390, P<0.0001). However, this was not part of the primary end point" - it won't be the case and "After much debate, the trial's executive committee decided the trial should continue"
- JUPITER: "criticism is that “soft” end points were used as the basis to stop the trial" - we know that hard endpoint should (expected to) be more than soft in R-IT
- "DMCs must not only consider statistical stopping guidelines when making decisions regarding the early termination of a trial for benefit, but they also must consider the uptake and acceptance of the result by the clinical community. If the data are relatively insubstantial, clinicians are skeptical of the results, and the trial may be viewed as an unnecessary loss of time, resources and, potentially, lives." - R-IT will be stopped as "based on the design of REDUCE-IT, given the high thresholds of overwhelming efficacy and safety, and the robustness and consistency typically required to be achieved across key secondary endpoints and patient subgroups prior to an independent DMC recommending an early stop", so it won't be an issue

These were my guess due to lack of any specification from you ...

Best,
G