Part 2: Journal ignores evidence of misconduct in ticagrelor studies
After publishing two key studies, the journal Circulation has deflected responsibility amid evidence of scientific misconduct—missing data, outcome switching, and authorship irregularities.
Circulation—one of cardiology’s leading journals and the flagship publication of the American Heart Association—has refused to act on serious concerns raised about two key studies used to promote AstraZeneca’s anti-clotting drug, ticagrelor.
The studies were instrumental in portraying ticagrelor as ‘faster and more potent’ than its cheaper rival, clopidogrel—a message that fuelled its widespread use and cemented its place in clinical guidelines worldwide.
But as detailed in Part 1, both studies contain major irregularities.
An investigation by The BMJ’s Dr Peter Doshi alleged scientific misconduct, citing undisclosed changes to primary endpoints, missing platelet data submitted to the FDA, and serious questions surrounding authorship of the research.
Circulation passes the buck
When asked whether it would investigate the anomalies in the published studies, Circulation deflected responsibility.
It is the sole responsibility of the individual researchers and their institutions to review and approve all publications submitted to American Heart Association scientific journals… The responsibility to investigate allegations of errors or misconduct rests solely with the institution/s and the investigator/s involved—not the journals.
The journal invoked “scientific publishing best practices,” yet failed to take even the most basic editorial steps.
In the RESPOND study, for example, researchers changed the primary endpoint without disclosure. The original outcome showed no benefit for ticagrelor (P=0.157), but the published paper reported a more favourable outcome (P=0.005).
A simple comparison between the original protocol and the final publication would have exposed the discrepancy—but Circulation never checked.
Nor did it issue an expression of concern, a safeguard explicitly recommended by the Committee on Publication Ethics (COPE) when doubts arise about a study’s reliability.
COPE’s guidance is clear: journals that receive credible concerns should inform their readers.
So far, Circulation has done nothing.
When journals fail, who steps in?
Dr Richard Smith, former editor-in-chief of The BMJ, said that while journals may not be legally empowered to conduct formal investigations, they still bear responsibility when serious concerns are raised.
“Flawed or fraudulent papers can certainly create safety issues,” he said. “So I think that a journal that has published papers that may be flawed or fraudulent should alert their readers.”
He suggested that journals could publish an editorial outlining the doubts—particularly since institutional investigations often take years, if they happen at all.
“They have a duty to ensure that an investigation does take place and that the results are shared, and actions taken if necessary,” he added. “Often in my experience institutions failed to investigate adequately, and there may come a point when the journal needs to say something.”
Smith pointed to a precedent.
The BMJ issued an expression of concern in the case of researcher Ram B. Singh, whose work came under scrutiny but was never formally investigated by any institution in India.
Protecting journals, not patients
Cardiologist and research integrity advocate Dr Peter Wilmshurst said Circulation’s response is emblematic of a broader dysfunction in scientific publishing.
“‘Scientific publishing best practices’ are designed to protect journals and publishers, not patients and the public,” he said.
He argued that responsibility cannot be handballed back to the very authors and sponsors with the most to lose—and expect that they will investigate themselves.
“Those groups have the greatest reputational and financial incentives to cover up errors and misconduct,” he said.
Wilmshurst was particularly critical of Circulation’s role in promoting ticagrelor. Alongside the RESPOND study, the journal published a “Clinical Perspective”—a type of editorial summary that reinforced the drug’s marketing claims.
“These summaries often read like company advertisements,” he said.
Raising questions about a study’s integrity, Wilmshurst argued, could have jeopardised the journal’s financial relationship with AstraZeneca.
He said, “AstraZeneca would have been unlikely to purchase reprints if the publications revealed safety concerns.”
And reprint sales can be lucrative—medical journals often earn significant revenue from drug companies distributing reprints to clinicians as marketing tools.
Regulators look the other way
The journal is not the only institution failing to act.
I asked the US Food and Drug Administration (FDA) what steps it would take to address the missing data uncovered by Doshi’s investigation.
Submitting false or incomplete data to a regulator is a serious offence, potentially constituting fraud. But the FDA showed little interest.
A spokesperson for the Department of Health and Human Services (HHS), the FDA’s parent agency, responded:
The FDA is unable to comment on specific conclusions or questions related to data from third-party sources, for which the FDA cannot validate the values or methodology.
The response suggests the agency will neither pursue Doshi’s findings nor examine whether AstraZeneca misled regulators.
Stonewalling becomes the norm
Speaking on The BMJ’s Medicine & Science podcast, Doshi said the refusal of journals and investigators to address well-documented concerns reflects a wider culture of evasion.
“You have to break through the stonewalling,” he said. “It cannot be the end of the story that the investigators responsible for this simply refuse to speak. The journals refuse to act. That cannot be the end of this.”
He argued that meaningful accountability might require legal authority.
“You absolutely need some kind of institution with subpoena authority to make people discuss—to have them show us their records. That is what I see as absolutely needed. I see no alternative, and patients deserve no less,” Doshi said.
A crisis of trust
Rita Redberg, cardiologist and former editor of JAMA Internal Medicine, echoed those concerns on the podcast.
“I think it's important to have an accurate record,” she said. “The original FDA approval needs to be accurate and based on accurate data. What’s in the literature needs to be accurate. And our guidelines need to be based on accurate data.”
Redberg warned that the damage goes far beyond a single drug.
“The bigger issue is, how do we know this hasn’t happened with other drugs that haven’t been investigated? It undermines trust in the system,” she said.
BMJ editor-in-chief Kamran Abbasi reinforced the point: “It’s the duty of a journal and its editorial team to take it seriously and correct the record. That’s fundamentally what’s important here.”
Journals profit, patients lose
Despite mounting evidence of flaws in ticagrelor research, Circulation has issued no retraction, no correction—not even a formal expression of concern.
The journal maintains that the responsibility lies elsewhere.
But scientific journals do more than publish research. They confer legitimacy. They shape medical norms. They influence clinical decisions. And they profit from the material they publish.
If journals refuse to act when credible allegations of misconduct arise—and regulators decline to investigate whether they were misled—then who is left to protect the public?
See Part 1: BMJ Investigation reveals serious flaws in trials of blockbuster anti-clotting drug. [FULL STORY]
I thought I was prescribed the best treatment after a stent and now I find the science for approval was not gold standard but accepted by the regulators/commercial big pharma consortium
In whom we trust…
Thanks Maryanne for your vigilant reporting - sad media big pharma and regulators appear to love $$$ too much
Interesting - Newspapers print retractions or corrections when they have found to have reported incorrectly. I would think that one of the reasons behind this is to uphold their reputation for ensuring only accurate and correct reporting occurs (apart from legal concerns).
Circulation, by utterly failing to provide any guidance to its readers in this case shows it has no ethics and that any future articles/papers/editorials should be treated with total suspicion. In fact I would go so far as to say that anybody who now reads Circulation is deluded if they believe they can trust any of the content.
Years ago I ceased reading the "New Scientist" (probably better named the "Non Scientist") after its recklessly politically based reporting on covid and climate change for this same reason, as countless articles could easily be seen to be false or reporting on basically fraudulent studies.
There is a business opportunity here for the journals. Report accurately and fearlessly , and issue retractions and warnings - but basically become the "go to" place if one wants trusted reporting. Food for thought...