A recent BMJ investigation exposes serious doubts regarding ticagrelor data integrity in pivotal studies that contributed to the approval and widespread use of AstraZeneca’s antiplatelet drug ticagrelor (marketed as Brilinta or Brilique). The article reveals significant misreporting and missing data within key platelet function trials, ONSET/OFFSET and RESPOND. These issues, alongside previously reported problems in the landmark PLATO trial, raise profound questions about the scientific foundation for ticagrelor’s perceived clinical benefits over less costly alternatives.

Data Integrity Exposed: Flaws in Platelet Function Trials

The most impactful finding of the BMJ report is the identification of major discrepancies in the reporting and conduct of two foundational trials, ONSET/OFFSET and RESPOND. These trials were used to demonstrate ticagrelor’s rapid and consistent platelet inhibition following acute coronary events. Specific examples include inaccurate reporting of primary endpoints in the journal Circulation. The absence of over 60 platelet machine readings in FDA-submitted datasets and inconsistencies regarding trial authorship were also noted. For instance, one listed author denied participation, while an active investigator was not credited. The BMJ’s access to raw laboratory readouts showed missing data points were disproportionately higher in platelet activity, suggesting possible bias in data selection.

Concerns deepen due to the technical complexities of multicenter platelet function studies. These require rigorous quality control and training due to the susceptibility of aggregation results to artefactual variation. The investigation could not confirm whether all sites received proper laboratory training, undermining confidence in the findings. Also, the protocol-specified primary endpoint for RESPOND failed to achieve statistical significance. Yet, it was published with a changed endpoint that reached significance without disclosure—a practice inconsistent with scientific standards.

Historical Context: Past Concerns Highlighted

Doubts about the foundational PLATO trial were previously raised, including by FDA reviewers who found paradoxes in the claimed mechanism and clinical outcomes. AstraZeneca asserted ticagrelor’s superiority over clopidogrel, but independent reviewers noted patient subgroups expected to benefit most did not show improved outcomes. This contradicted the pharmacodynamic narrative presented by company-sponsored studies. The BMJ’s expansion of its inquiry into the platelet studies reveals a broader pattern of reporting and transparency deficiencies. Regulatory authorities and the scientific community have flagged these issues before but not resolved them.

Significant Implications for Health Economics and Regulatory Oversight

The exposure of unresolved ticagrelor data integrity problems in studies underpinning a multibillion-dollar global therapy has significant implications. Inaccurate or incomplete evidence supporting a branded drug’s benefit over cheaper alternatives can distort formulary decisions and inflate health system costs. It also undermines public trust in regulatory approval processes. Prescription drug spending remains one of the fastest-growing categories in healthcare expenditure, with year-over-year increases. Reliance on flawed or misreported clinical evidence has direct financial ramifications for payers and patients.

For reimbursement and pricing, such revelations heighten the need for real-world evidence and independent data reanalyses. They also call for greater transparency in trial reporting. These issues contribute to the debate about post-marketing surveillance and the potential rescinding of approvals where foundational evidence is compromised. Industry and regulatory bodies may face increased demands for data sharing and external validation. There may also be calls to revisit health technology assessments for high-cost drugs with questionable clinical value.

In conclusion, the BMJ’s findings regarding ticagrelor’s supporting trials raise fundamental questions. These concern not only AstraZeneca’s antiplatelet therapy but also broader systemic vulnerabilities in the evaluation and reimbursement of innovative therapies. As generic versions of ticagrelor enter the market, stakeholders—including regulators, payers, and health economists—must reassess both legacy and future evidence. This is necessary to safeguard value, patient safety, and credibility in evidence-based decision-making. For more information on these pivotal findings, refer to the original article published in the BMJ.