A blockbuster heart drug trusted by millions is facing renewed scrutiny. As generic ticagrelor prepares to hit the market, new evidence raises urgent questions about the data that launched AstraZeneca’s billion-dollar therapy.
Key Points at a Glance
- BMJ investigation uncovers major inaccuracies in key ticagrelor trials—casting doubt on the drug’s reported benefits.
- Missing data, unreported adjustments, and statistical manipulation were identified in multiple clinical studies.
- Some study authors had no actual involvement; others could not be reached or declined to comment.
- The findings raise serious questions about trial oversight and the approval process for high-impact drugs.
For more than a decade, AstraZeneca’s ticagrelor (Brilinta/Brilique) has been a mainstay in the treatment of acute coronary syndrome. Now, with generic versions set to enter the market, a new investigation by The BMJ is forcing doctors, patients, and regulators to re-examine the drug’s scientific foundations.
At the heart of the controversy are two pivotal platelet studies—ONSET/OFFSET and RESPOND—published in Circulation, which have long been cited as proof of ticagrelor’s rapid and superior platelet inhibition. However, the BMJ’s analysis reveals a troubling landscape: primary endpoints were misreported, more than 60 lab readings were absent from FDA datasets, and key authors named on the studies either weren’t involved or could not be contacted. Most of the trial’s investigators, including principal authors, declined interviews or were unreachable, deepening the mystery and raising alarms about transparency.
Questions first surfaced after a 2023 BMJ exposé highlighted data integrity issues in PLATO, the 18,000-patient trial that led to ticagrelor’s global approval. Building on these concerns, the latest investigation scrutinized the design, execution, and reporting of ONSET/OFFSET and RESPOND. Among the findings: in one trial, results that failed to reach statistical significance were published as significant, following a post-hoc change in primary endpoint definition. More than a quarter of platelet activity readings stored in lab machines never made it into the official FDA record—those left out were, on average, significantly higher than included data.
Clinical trial experts interviewed by The BMJ noted the extreme demands on participants, who endured unusually high numbers of blood draws, often without compensation. Some trial sites struggled to enroll or retain subjects. Internal documents revealed unclear records, and discrepancies in machine shipping, test kit supply, and data entry timelines. In several cases, baseline readings were missing, yet additional samples were still taken, resulting in questionable patient inclusion and exclusion. Data adjustments that could have skewed the findings were not disclosed in published reports.
Perhaps most alarming, some listed co-authors told The BMJ they had no role in the studies, while experienced researchers could not verify whether sites received appropriate laboratory training for complex, artifact-prone platelet assays. The use of a multicenter design, usually a marker of robust methodology, added another layer of complexity and risk for errors if training and protocols weren’t tightly standardized.
Despite these red flags, AstraZeneca has maintained confidence in its data. Yet, regulatory concerns have simmered for years—one FDA reviewer noted ticagrelor patients undergoing early invasive procedures actually fared worse than those on clopidogrel, contradicting company claims about the drug’s advantages. The BMJ’s investigation now suggests these discrepancies go beyond interpretation, touching on the very foundation of trial reliability and drug approval standards.
As generics of ticagrelor arrive and clinicians re-evaluate prescribing practices, the medical community faces difficult questions: How can we ensure the integrity of future clinical trials? Are current regulatory safeguards enough to prevent flawed or manipulated data from influencing patient care at scale? For patients and physicians, trust in science has never been more vital—or more at stake.
Source: The BMJ
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