Article Impact Level: HIGH Data Quality: STRONG Summary of BMJ, q2550. https://doi.org/10.1136/bmj.q2550 Peter Doshi et al.
Points
- The PLATO trial, the key to the approval of ticagrelor, is under scrutiny due to data integrity concerns and inconsistent findings, notably higher mortality among U.S. patients.
- Significant issues in the trial include omitted deaths, inaccurate reporting, and potential biases, especially at sites monitored by third-party organizations versus AstraZeneca-monitored sites.
- Subsequent studies have failed to replicate the PLATO trial’s positive outcomes, raising doubts about ticagrelor’s superiority over clopidogrel.
- Experts advocate for reevaluating ticagrelor’s role in clinical practice, emphasizing its high cost and inconsistent evidence of benefit over cheaper alternatives.
- The controversy underscores the critical need for data transparency and accuracy in clinical trials to maintain public health trust and accountability.
Summary
The PLATO trial, a pivotal study for the approval of ticagrelor (Brilinta/Brilique) as an antiplatelet drug for acute coronary syndrome, is under increasing scrutiny due to data integrity and the validity of its findings. Published in 2009, the trial demonstrated that ticagrelor reduced cardiovascular events compared to clopidogrel. However, the results were inconsistent, especially in U.S. patients, where ticagrelor was associated with higher mortality. Despite objections from the FDA’s medical officer regarding data quality, the FDA approved ticagrelor in 2011. Post-approval studies have failed to replicate the trial’s positive outcomes, prompting further investigation into the reliability of the trial data.
A recent analysis by The BMJ highlighted significant discrepancies in the PLATO trial’s data, including inconsistencies in patient deaths and reporting accuracy. For example, 45 deaths were omitted from the published New England Journal of Medicine results. The trial’s findings were also questioned due to potential biases, such as those at sites monitored by third-party research organizations, where ticagrelor performed worse than sites overseen by AstraZeneca. These concerns were further explored in a 2013 investigation by the U.S. Department of Justice, which, despite closing in 2014, left lingering doubts about the trial’s integrity.
Experts, including Victor Serebruany from Johns Hopkins, call for a reappraisal of ticagrelor’s place in clinical practice in light of the unresolved issues with the PLATO trial. The ongoing controversy emphasizes the need for transparency and data accuracy in clinical trials, particularly for drugs as costly as ticagrelor, which has not consistently demonstrated superior efficacy over less expensive alternatives. Critics continue to urge further investigation into the trial’s data to ensure public health safety and accountability.
Link to the article: https://www.bmj.com/content/387/bmj.q2550
References Doshi, P. (2024). Doubts over landmark heart drug trial: Ticagrelor PLATO study. BMJ, q2550. https://doi.org/10.1136/bmj.q2550
