BMJ Investigation Uncovers Data Integrity Issues in AstraZeneca's Ticagrelor Heart Drug Trials
核心洞察
A BMJ investigation has revealed evidence of serious misreporting in two clinical trials that were pivotal to ticagrelor's approval by the FDA and UK regulators.
The investigation found that primary endpoint results were inaccurately reported in the journal Circulation, and more than 60 of 282 platelet machine readings were missing from FDA datasets.
Experts warn that millions of patients taking the anti-clotting drug may be receiving a treatment that is less effective than originally claimed, with some studies suggesting it may increase risks.
A new investigation by The BMJ has uncovered evidence of serious data misreporting in clinical trials that led to the approval of ticagrelor, AstraZeneca's blockbuster heart drug prescribed to millions of patients worldwide. The findings raise fresh concerns about whether the anti-clotting medication should have been authorized for use.
The investigation focused on two key platelet studies that AstraZeneca used to support ticagrelor's FDA approval. Researchers found that the "primary endpoint" results—the trial's key measurement used to determine treatment effectiveness—were inaccurately reported in the leading cardiology journal Circulation.
Missing Data Raises Red Flags
Perhaps most concerning, the BMJ analysis revealed that more than 60 of 282 readings from platelet machines used in the trials were not present in the datasets submitted to the FDA. According to the investigation, "the platelet activity levels not entered were significantly higher than those used in the Circulation papers and FDA datasets."
The missing data included instances where patients' blood "platelet aggregation dramatically increased," a condition where platelets (搜索) stick together to form clumps that can lead to blood clots—exactly what the drug is designed to prevent. The BMJ noted this "suggests incorrect laboratory readings."
Dr. Victor Serebruany, an expert in cardiovascular pharmacology at Johns Hopkins University who has been critical of the drug for over a decade, told The BMJ: "It's been obvious for years that there is something wrong with the data. That the FDA's leadership could look past all these problems—on top of the many problems their own reviewers identified and are now being discovered by The BMJ—is unconscionable."
Widespread Clinical Use Despite Concerns
Ticagrelor, sold as Brilinta in the US and Brilique in Europe, was approved for NHS use in 2011 after trials appeared to show it could prevent one in five deaths after a heart attack (搜索). The twice-daily pill is prescribed to people with acute coronary syndrome (搜索), which includes heart attack survivors and those with severe angina (搜索).
In the UK alone, the drug is prescribed around 45,000 times per month on the NHS. According to the National Institute for Health and Care Excellence (NICE), patients are advised to take 90mg twice daily for around a year after a heart attack (搜索), with a lower 60mg dose potentially prescribed for up to three additional years.
Growing Scientific Skepticism
Since ticagrelor's initial approval, multiple studies have cast doubt on whether the AstraZeneca drug is as effective as its rivals, such as clopidogrel. Some research has even suggested the medication may increase certain risks for patients.
This latest BMJ investigation builds on previous concerns raised about the drug's landmark PLATO trial, which was used to gain worldwide approval. Last December, The BMJ found serious data integrity problems in that pivotal study, calling into question ticagrelor's advantage over cheaper alternatives.
Industry Response and Ongoing Questions
The investigation also revealed irregularities in the research team composition. One active trial investigator never became a study author, while one listed author told The BMJ he was not involved in the trial. Most investigators, including the principal investigator, were either unreachable or declined to be interviewed.
Dr. Serebruany emphasized the clinical implications: "There are episodes of skyrocketing rebound and profound platelet inhibition after ticagrelor making patients prone to thrombosis or bleeding. If doctors had known what happened in these trials, they would never have started using ticagrelor."
A spokesperson for the Sinai Center for Thrombosis Research and Drug Development (搜索), led by Dr. Paul Gurbel who conducted the trials, stated that "any allegations of any research misconduct in the two studies are baseless and erroneous."
An AstraZeneca spokesperson maintained confidence in the drug, telling media outlets: "We are confident in the integrity of the trials and its evidence in support for Brilinta." However, both Circulation journal and AstraZeneca did not respond to The BMJ's requests for comment regarding the specific findings.
As generic versions of ticagrelor prepare to launch this year, these revelations add to mounting questions about the drug's regulatory approval process and ongoing clinical use in treating cardiovascular conditions.