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.