BMJ investigation raises new concerns over ticagrelor approval trials

In a follow up investigation into the multibillion dollar drug ticagrelor, The BMJ has uncovered fresh concerns, this time in key platelet studies used in its FDA approval. 

For more than a decade, ticagrelor (Brilinta in the US and Brilique in Europe) has been recommended for patients with acute coronary syndrome - a range of conditions related to sudden reduced blood flow to the heart.

Last December, an investigation by The BMJ found serious data integrity problems in the landmark clinical trial (PLATO) that was used to gain worldwide approval for ticagrelor, calling into question the drug's advantage over cheaper rivals.

Now, as generic versions of the drug prepare to launch this year, The BMJ has expanded its investigation, looking at two key platelet studies that AstraZeneca claimed explained ticagrelor's ability to treat acute coronary syndrome successfully. 

It finds that the "primary endpoint" results (the trial's key measurement) for both clinical trials were inaccurately reported in the leading cardiology journal Circulation, and reveals that more than 60 of 282 readings from platelet machines used in the trials were not present in US Food and Drug Administration (FDA) datasets.

What's more, one active trial investigator never became a study author, while one author told The BMJ he was not involved in the trial, and most investigators, including the principal investigator, were unreachable or declined to be interviewed.

Victor Serebruany, an adjunct faculty member at Johns Hopkins University and ticagrelor's most renowned critic, told The BMJ that "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."

Circulation and AstraZeneca did not respond to a request for comment.

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. We all need to know how and why that happened."

Victor Serebruany, adjunct faculty member, Johns Hopkins University