Explosive Revelations Challenge the Integrity of PLATO Trial Data for Ticagrelor

An investigation released through The BMJ these days has raised substantial worries regarding the landmark scientific trial (PLATO) that helped secure international acclaim for ticagrelor, an anti-platelet drug marketed as Brilinta inside the US and Brilique in Europe, synthetic with the aid of AstraZeneca.

Peter Doshi, senior editor at The BMJ, has uncovered new details that factor to potential problems with how records became pronounced. Through a freedom of facts request, Doshi gained get admission to to primary PLATO trial records and unpublished information, losing mild on discrepancies inside the reporting system.

Originally posted in the *New England Journal of Medicine* (NEJM) in 2009, the PLATO trial involved over 18,000 patients throughout 43 countries. The observe concluded that ticagrelor decreased deaths from vascular causes, heart attacks, and strokes whilst compared to clopidogrel (Plavix). However, facts from US sufferers indicated higher mortality quotes within the ticagrelor organization, main to AstraZeneca’s preliminary failure to acquire FDA approval.

In response to AstraZeneca’s resubmission, FDA scientific officer Thomas Marciniak criticized the submission, calling it “the worst in my experience concerning completeness” and expressed issues over the reliability of the trial’s facts. Despite these objections, the FDA accredited ticagrelor in 2011 for acute coronary syndrome, sparking a prolonged dispute over the trial’s findings. Since then, numerous studies have struggled to replicate PLATO’s high-quality results, main experts to impeach the validity of the trial’s conclusions and to name for a re-assessment of the drug’s status in remedy recommendations.

Victor Serebruany, a researcher at Johns Hopkins University, changed into initially impressed with the trial consequences but have become skeptical after noticing inconsistencies within the facts. This led him to guide a US Department of Justice investigation into the PLATO trial in 2013.

Eric Bates, from the University of Michigan and a co-author of the US guidelines recommending ticagrelor, has voiced concerns over the lack of substantial positive findings in subsequent trials. He is now advocating for a review of ticagrelor’s role in clinical guidelines.

Some critics have pointed out that the PLATO trial’s results were questionable from the outset, especially given that ticagrelor performed worse at sites monitored by third-party contract research organizations (CROs) compared to those overseen by AstraZeneca.

Co-chairs of the PLATO trial, Robert Harrington and Lars Wallentin, have argued that there is no reason to believe the monitoring organizations influenced the outcomes, citing an analysis conducted by two senior academic statisticians.

The BMJ investigation also reveals discrepancies in the reported number of deaths, their causes, and the dates when they occurred, raising further concerns about the accuracy of the data submitted to the FDA and the possibility of unblinding.

AstraZeneca declined to comment on the investigation. A company spokesperson responded by directing The BMJ to a public statement from 2014 following the US Department of Justice’s investigation. The trial co-chairs, Harrington and Wallentin, did not respond to requests for comment from The BMJ.

Additionally, The BMJ‘s analysis found that the number of deaths reported in the NEJM paper was incomplete. The NEJM acknowledged this issue but stated that if they could not reach the authors or access the data, they likely would not proceed with corrections.

Fifteen years after the PLATO trial, Serebruany continues to raise concerns about the data’s integrity. In an interview with The BMJ, he expressed little hope that scientific channels alone would resolve these issues, suggesting that renewed involvement from the US Department of Justice is the only path forward. He emphasized the need for a thorough investigation and action, urging that it would provide justice for the American public.