BMJ Investigation Finds More Concerns in Ticagrelor Trials
BMJ Investigation Finds More Concerns in Ticagrelor Trials
Date: June 19 , 2025
Source: The BMJ
Scientific Summary (Key Points):
1. Context:
A new BMJ investigation raises serious concerns about the integrity of clinical trials that led to the approval of ticagrelor (Brilinta), especially as generics are now entering the market.
2. Lead Investigator:
Peter Doshi, PhD, senior editor at The BMJ, questions the reliability of data from key studies: PLATO (2009), ONSET/OFFSET, and RESPOND.
3. Key Findings:
• PLATO study (NEJM 2009): Previously criticized for data inconsistencies and omissions.
• RESPOND trial: Originally nonsignificant primary outcome (P = 0.157) was changed without disclosure and later reported as significant (P = 0.005) in Circulation.
• ONSET/OFFSET trial: Patient exclusions were not reported transparently; labeled as “intention-to-treat” despite exclusions. Implausible data were transformed through unpublished analysis.
4. Missing FDA Data:
• Doshi reviewed platelet function machine outputs and found 60+ out of 282 readings missing from the FDA-submitted dataset.
• These omitted data showed significantly higher platelet activity than reported, suggesting rebound effects that could raise risks of thrombosis or bleeding.
5. Authorship Concerns:
• A trial investigator was not listed as an author.
• One listed author claimed he was not involved in the study.
6. Reactions:
• Dr. Victor Serebruany (Johns Hopkins): Warned that if physicians had known the full data, “they would never have used ticagrelor.”
• Dr. Eric Bates (University of Michigan): Suggested the clinical support for ticagrelor over clopidogrel may be overstated and now recommends guideline review.
7. Industry Response:
• AstraZeneca, Circulation, and several original investigators declined to comment or were unreachable.
8. Regulatory Background:
• Ticagrelor faced an initial FDA rejection and a US DOJ investigation in 2013 (closed in 2014 without action