EMA Investigating Validity of Clinical Trial Led by FDA Commissioner Nominee

Regulatory NewsRegulatory News | 03 December 2015 |  By 

The European Medicines Agency (EMA) has told Focus that it’s currently investigating whether a medical device defect may have had an impact on a major clinical trial that was designed and overseen by FDA commissioner nominee Robert Califf and ultimately led to the drug’s FDA and EMA approvals.

The trial, which compared the anti-clotting drug Xarelto (rivaroxaban) for patients with irregular heartbeat with warfarin, used an INR (International Normalized Ratio) device to measure blood clotting in patients taking warfarin. That device, known as the Alere INRatio and INRatio2 PT/INR Monitor System -- was part of a class I FDA recall about a year ago.

EMA spokeswoman Rebecca Harding told Focus that the manufacturer of Xarelto – Bayer -- recently informed the agency that the defect in the INR device could have an impact on the study results.

“Due to the defect, it is now thought that the INR device has impacted the clotting results measured for the warfarin arm, which might affect the overall results for Xarelto as compared with warfarin,” Harding said in an email.

And what could be potentially troubling for Califf, as first reported by POGO, is that he was listed on the European Heart Journal study as one of two doctors (when he worked for the Duke Clinical Research Institute) who oversaw and designed the trial. However, no US senators have said that the trial’s issues could be a deal-breaker for making him FDA commissioner (although Republican Sen. Lisa Murkowsi of Alaska did say she wouldn't vote for Califf because FDA approved genetically modified salmon).

For now, EMA’s Committee for Medicinal Products for Human Use (CHMP) is reviewing the data related to the INR device used in what is known as the Rocket trial. CHMP is investigating “whether the data generated from the INRatio device could have had any impact on the Rocket trial results and the extent of this impact, if applicable,” Harding said.

The finalization of the CHMP assessment is planned for early 2016. 

Sanjay Kaul of Cedars-Sinai Medical Center in Los Angeles, who served on the FDA advisory panel that raised serious questions but ultimately called for the approval of Xarelto, told CardioBrief that "the key issue is whether there was any malfeasance with regards to INR assessment (or data ascertainment). EMA has asked for information from the sponsors and it deserves to be given some time to scrutinize it. Until the results of this investigation come out, we should not prejudge the issue."


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