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Device Used in Trial That Was Overseen by FDA Nominee Is Linked to Thousands of Reports of Injuries and Malfunction, Public Citizen Analysis Shows

Dec. 10, 2015

Device Used in Trial That Was Overseen by FDA Nominee Is Linked to Thousands of Reports of Injuries and Malfunction, Public Citizen Analysis Shows

New Safety Information Raises Questions About Califf’s Industry Ties, Decision to Use Device

WASHINGTON, D.C. – A blood testing device used in an industry-funded clinical trial – overseen by a company steering committee co-chaired by U.S. Food and Drug Administration (FDA) commissioner nominee Robert Califf – has been the subject of 9,469 malfunction reports and 1,445 injury reports since the original marketing of the device in 2002, a Public Citizen analysis of FDA records shows.

The new data about the INRatio device’s inaccurate measurements and safety raise questions about Califf’s participation in the decision to use it in the trial, called ROCKET AF, which was started more than nine years ago and funded by Johnson & Johnson.

False readings by the blood testing device could have skewed the trial results in favor of the new blood thinner (anticoagulant) being tested – rivaroxaban (brand name Xarelto), made by Bayer, Public Citizen said.

The injury and malfunction reports related to the device occurred in people not in the trial. Public Citizen sent the new information today in a letter to the FDA, which is reviewing the trial, and the European Medicines Agency (EMA), which is investigating the trial. The letter was co-written by Dr. Frits Rosendaal, a noted authority from the Netherlands on measuring the effects of anticoagulants and on the safety and efficacy of medications used to prevent strokes and heart attacks.

The INRatio device played a critically important role in the ROCKET AF trial – which compared the safety and effectiveness of the blood thinner warfarin with the newer drug Xarelto for preventing strokes in people with atrial fibrillation, a common abnormal heart rhythm. INRatio device measurements were used to adjust the dose of warfarin in patients who were assigned to that treatment during the trial. Based on the results of the trial, the FDA approved Xarelto four years ago.

Commenting to a reporter this week on its investigation, an EMA spokesperson said, “Due to the defect, it is now thought that the INR device has impacted the clotting results measured for the warfarin arm [in the ROCKET AF trial], which might affect the overall results for Xarelto as compared with warfarin.”

Califf had extensive financial ties to drug and medical device companies during his tenure at Duke University. Public Citizen maintains that because of his close relationships with these FDA-regulated industries over more than two decades, Califf is unfit to head the agency.

“Hundreds of reports of injuries or malfunctions with the INRatio device occurred before this trial started,” said Dr. Sidney Wolfe, co-founder and senior adviser of Public Citizen’s Health Research Group. “The device was known to give faulty readings and injure patients. Why did Dr. Califf and the steering committee that he co-chaired agree to use it in the trial? This adds to the view that Dr. Califf is not an appropriate candidate for FDA commissioner.”

Before the trial began, the INRatio device was the subject of two FDA warning letters about the device’s propensity to give falsely low or high blood coagulation readings, and was the subject of a recall warning notice after the trial ended.

Public Citizen today also called for:

  • Califf to recuse himself from the ongoing FDA review of this matter;
  • Califf to explain why the clinical trial researchers decided to use the device, given its history of causing injury and malfunctioning in other patients prior to the trial;
  • The FDA to thoroughly investigate the implications of the faulty medical device on the results of the ROCKET AF trial; and
  • The FDA to examine whether to pull the device from the market in light of the ongoing harm to patients using it.

“In this trial, rivaroxaban was compared with warfarin, which was monitored in a substandard way. This may not only have harmed patients, but also sheds doubts on the outcome of the trial regarding whether rivaroxaban is as good as warfarin for treating the kinds of patients studied in the trial,” Rosendaal said.