IMPRESSION
As of today, the evidence suggests that the FDA-issued and Investigators
datasets for PLATO deaths were different and do not match. Because the
FDA appears to have erroneously judged and approved ticagrelor based on
inaccurate death reports, the main message of this paper is to call for
a match. Importantly, 905 deaths reported in almost 100 of papers in top
journals by PLATO Investigators should be identical with the FDA report.
However, it seems that primary death causes, especially vascular ones,
were misreported or flawed in some way independent from the FDA
submission. Moreover, the death classification codes applied were
different as well and it is unclear why such efforts were not
synchronized with the FDA. The current scenario looks like parallel
reality. One inaccurate death list is provided to the FDA for gaining
regulatory approval, while another different dataset with even more
favorable ticagrelor benefit is issued to trial investigators that may
have led to multiple false-positive reports. We are kindly asking the
ticagrelor sponsor or/and concerned PLATO Investigators to help us with
the deaths dataset clarification.
Acknowledgements: Our true appreciation to clinical and
statistical FDA reviewers on ticagrelor New Drug Application 22-433 for
their integrity and courage with the “no approval” recommendation. At
the time of NDA 22-433 review, the senior author of this paper was a
Medical Team Leader for the FDA cardio-renal division. These findings
reflect our own knowledge, based on Task Force analyses, and are not the
opinions of Johns Hopkins University or Montreal Heart Institute. Drs.
Serebruany and Marciniak but not
Dr. Tanguay had full access to the FDA-issued PLATO death list.
Conflicts of Interest: None.