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The pharmaceutical companies developing the anticoagulant rivaroxaban (Xarelto) withheld information about the system used to measure international normalized ratios (INRs) in the ROCKET AF trial, according to an investigation published in The BMJ.
ROCKET AF was used to support the approval of rivaroxaban in the US and European Union, and the Alere INRatio Monitor System was used to measure INRs in the warfarin arm of the trial.
The system was later recalled because it was shown to provide falsely low test results.
The BMJ said Janssen and Bayer, the companies developing rivaroxaban, knew about concerns regarding the accuracy of the INRatio system while ROCKET AF was underway but allowed the system to be used in the trial anyway.
The companies also neglected to mention these concerns to regulatory authorities prior to rivaroxaban’s approval and later failed to notify regulators about the recall of the INRatio system and its potential impact on ROCKET AF.
In addition, Janssen, which was responsible for conducting ROCKET AF, did not tell regulators about a safety program the company launched during the trial to address concerns about the INRatio system.
In fact, The BMJ’s investigation suggests Janssen kept this program a secret from ROCKET AF investigators, the trial’s data and safety monitoring board, and Bayer.
How the events unfolded
ROCKET AF, which was launched in February 2007, was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.
Results from the trial, published in NEJM in August 2011, suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
These results were used to support the approval of rivaroxaban in the European Union in September 2011 and in the US in November 2011.
A number of critics, including The BMJ, have questioned the results of ROCKET AF because the INRatio system (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) has been shown to give falsely low test results.
The system was recalled for certain patients in December 2014 and was withdrawn from the market in July 2016.
The BMJ said Janssen and Bayer did not inform regulatory authorities about the December 2014 recall—and how issues with the INRatio system may have affected ROCKET AF—until The BMJ probed them in September 2015.
Once the authorities knew, they launched investigations. In February 2016, the European Medicine’s Agency (EMA) released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.
The US Food and Drug Administration (FDA) is still conducting its investigation but has not changed its recommendations regarding rivaroxaban.
The BMJ also reported that ROCKET AF’s executive committee and trial investigators raised concerns about the INRatio system shortly after the trial began.
Both Janssen and Bayer were aware of these concerns but did not disclose them to the FDA or EMA before rivaroxaban was approved.
Instead, Janssen launched the Covance recheck program in early 2008. This safety program involved an unblinded monitor checking INRatio readings against lab results if an investigator had concerns about the INRatio system.
Janssen did not inform ROCKET AF investigators or the trial’s data and safety monitoring board of the program. Bayer said it did not know about the program until this year, and the FDA and EMA have said the same. 
The pharmaceutical companies developing the anticoagulant rivaroxaban (Xarelto) withheld information about the system used to measure international normalized ratios (INRs) in the ROCKET AF trial, according to an investigation published in The BMJ.
ROCKET AF was used to support the approval of rivaroxaban in the US and European Union, and the Alere INRatio Monitor System was used to measure INRs in the warfarin arm of the trial.
The system was later recalled because it was shown to provide falsely low test results.
The BMJ said Janssen and Bayer, the companies developing rivaroxaban, knew about concerns regarding the accuracy of the INRatio system while ROCKET AF was underway but allowed the system to be used in the trial anyway.
The companies also neglected to mention these concerns to regulatory authorities prior to rivaroxaban’s approval and later failed to notify regulators about the recall of the INRatio system and its potential impact on ROCKET AF.
In addition, Janssen, which was responsible for conducting ROCKET AF, did not tell regulators about a safety program the company launched during the trial to address concerns about the INRatio system.
In fact, The BMJ’s investigation suggests Janssen kept this program a secret from ROCKET AF investigators, the trial’s data and safety monitoring board, and Bayer.
How the events unfolded
ROCKET AF, which was launched in February 2007, was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.
Results from the trial, published in NEJM in August 2011, suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
These results were used to support the approval of rivaroxaban in the European Union in September 2011 and in the US in November 2011.
A number of critics, including The BMJ, have questioned the results of ROCKET AF because the INRatio system (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) has been shown to give falsely low test results.
The system was recalled for certain patients in December 2014 and was withdrawn from the market in July 2016.
The BMJ said Janssen and Bayer did not inform regulatory authorities about the December 2014 recall—and how issues with the INRatio system may have affected ROCKET AF—until The BMJ probed them in September 2015.
Once the authorities knew, they launched investigations. In February 2016, the European Medicine’s Agency (EMA) released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.
The US Food and Drug Administration (FDA) is still conducting its investigation but has not changed its recommendations regarding rivaroxaban.
The BMJ also reported that ROCKET AF’s executive committee and trial investigators raised concerns about the INRatio system shortly after the trial began.
Both Janssen and Bayer were aware of these concerns but did not disclose them to the FDA or EMA before rivaroxaban was approved.
Instead, Janssen launched the Covance recheck program in early 2008. This safety program involved an unblinded monitor checking INRatio readings against lab results if an investigator had concerns about the INRatio system.
Janssen did not inform ROCKET AF investigators or the trial’s data and safety monitoring board of the program. Bayer said it did not know about the program until this year, and the FDA and EMA have said the same.
The pharmaceutical companies developing the anticoagulant rivaroxaban (Xarelto) withheld information about the system used to measure international normalized ratios (INRs) in the ROCKET AF trial, according to an investigation published in The BMJ.
ROCKET AF was used to support the approval of rivaroxaban in the US and European Union, and the Alere INRatio Monitor System was used to measure INRs in the warfarin arm of the trial.
The system was later recalled because it was shown to provide falsely low test results.
The BMJ said Janssen and Bayer, the companies developing rivaroxaban, knew about concerns regarding the accuracy of the INRatio system while ROCKET AF was underway but allowed the system to be used in the trial anyway.
The companies also neglected to mention these concerns to regulatory authorities prior to rivaroxaban’s approval and later failed to notify regulators about the recall of the INRatio system and its potential impact on ROCKET AF.
In addition, Janssen, which was responsible for conducting ROCKET AF, did not tell regulators about a safety program the company launched during the trial to address concerns about the INRatio system.
In fact, The BMJ’s investigation suggests Janssen kept this program a secret from ROCKET AF investigators, the trial’s data and safety monitoring board, and Bayer.
How the events unfolded
ROCKET AF, which was launched in February 2007, was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.
Results from the trial, published in NEJM in August 2011, suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
These results were used to support the approval of rivaroxaban in the European Union in September 2011 and in the US in November 2011.
A number of critics, including The BMJ, have questioned the results of ROCKET AF because the INRatio system (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) has been shown to give falsely low test results.
The system was recalled for certain patients in December 2014 and was withdrawn from the market in July 2016.
The BMJ said Janssen and Bayer did not inform regulatory authorities about the December 2014 recall—and how issues with the INRatio system may have affected ROCKET AF—until The BMJ probed them in September 2015.
Once the authorities knew, they launched investigations. In February 2016, the European Medicine’s Agency (EMA) released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.
The US Food and Drug Administration (FDA) is still conducting its investigation but has not changed its recommendations regarding rivaroxaban.
The BMJ also reported that ROCKET AF’s executive committee and trial investigators raised concerns about the INRatio system shortly after the trial began.
Both Janssen and Bayer were aware of these concerns but did not disclose them to the FDA or EMA before rivaroxaban was approved.
Instead, Janssen launched the Covance recheck program in early 2008. This safety program involved an unblinded monitor checking INRatio readings against lab results if an investigator had concerns about the INRatio system.
Janssen did not inform ROCKET AF investigators or the trial’s data and safety monitoring board of the program. Bayer said it did not know about the program until this year, and the FDA and EMA have said the same.