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# BMJ Says Questions Raised About Califf’s Xarelto Trial
- URL: https://www.fdaweb.com/bmj-says-questions-raised-about-califfs-xarelto-trial/
- Published: 2016-02-04T12:00:00.000Z
- Updated: 2026-09-15T02:33:33.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5134677

> *The BMJ* (formerly the *British Medical Journal*) says that doctors and scientists are saying that there should be an independent investigation into the Duke Clinical Research Institute ROCKET-AF trial supervised by FDA commissioner-nominee **Robert Califf** that was used to support Bayer’s Xarelto (rivaroxaban). The blood thinner, marketed in the U.S. by Johnson & Johnson’s Janssen unit, is indicated to prevent ischemic stroke in non-valvular atrial fibrillation. The call for an independent probe comes after *The BMJ* reported that the trial results could have been compromised through use of a recalled point-of-care device to measure international normalized ratio (INR) in trial patients taking warfarin. Faulty INRatio device readings could have led to patients receiving higher warfarin doses than needed, with a greater risk of bleeding.  
>  
> The journal [article](http://www.bmj.com/content/352/bmj.i575.full.pdf+html?ref=fdaweb.com) reviews its investigation into the issue and its conversations with regulators. It quotes an FDA decision memo in which two clinical reviewers recommended that the drug not be approved in the U.S. because “ROCKET provides inadequate information to assess the relative safety and efficacy of Xarelto in patients whose warfarin administration can be well-controlled.” However, the article says, the reviewers were seemingly unaware that there were other reasons to be concerned about the adequacy of the warfarin control in the ROCKET-AF trial.  
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> “In tracking the faulty recall and its potential effect on the outcomes of a global clinical trial, *The BMJ* has once again come across flaws in device regulation,” the article says. “A series of journal investigations have highlighted the lack of clinical data required by U.S. and Europe regulators for high-risk implants, such as metal-on-metal hips, before they are put on the market. They have also shown how slow regulators can be to act when problems do emerge and shown how oversight can be lacking on the performance diagnostic tests.  
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> The journal says it asked Johnson & Johnson, Bayer, and Duke if any investigator had complained about mismatched point of care and laboratory INR readings if someone had a bleed in the trial. None responded to the questions. The European Medicines Association says it has asked the companies for analyses and would consider any analyses by Duke as well.  
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> At the end of 2015, the Project on Government Oversight (POGO) [said](http://fdaweb.com/login.php?sa=v&aid=D5134014&searchWords=Rivaroxaban&cate=S&stid=%241%24W62.nG1.%24DPfG9d08FhG6.UevKWSZk0&ref=fdaweb.com) that Califf “helped lead a clinical trial that was sharply criticized by FDA reviewers and some outside advisors to the agency.” The trial was conducted when Califf was leading the Duke research institute that he helped found.  
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> POGO said that as commissioner, Califf would “hold considerable sway over decisions that affect the interests of the drug industry and the health and safety of the public. Dr. Califf’s handling of the Xarelto trial raises concerns about his judgment in overseeing the pharmaceutical industry.”  
>  
> The advocacy group also noted in a later [statement](http://fdaweb.com/login.php?sa=v&aid=D5133928&searchWords=Rivaroxaban&cate=S&stid=%241%24a1..bM0.%24Ldew.kgr.r0hp69Zd9qOh0&ref=fdaweb.com) that Duke was conducting an independent analysis of the trial data to understand what effect, if any, the potential device malfunction might have had in subpopulations and specific patient groups. *The BMJ* says that a Duke 12/2015 news release with a summary of the results of their “secondary analysis of the trial findings” said the findings “are consistent with the results from the original trial and do not alter the conclusions of ROCKET-AF — rivaroxaban is a reasonable alternative to warfarin and is non-inferior for the prevention of stroke and systemic embolism with less intracranial hemorrhage and fatal bleeding.”  
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> The journal then quotes former FDA clinical pharmacologist **Bob Powell** as saying that the Duke statement is “misleading” because of the lack of information. And Yale University professor of cardiology **Harlan Krumholz** is quoted that the research institute “is among the most respected research institutions, but this statement suggests that they know important information that relates to the ROCKET-AF trial but are delaying in disseminating the information until it can be published.”  
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> Krumholz said that Johnson & Johnson agreed to release data to his Yale University Open Data Access project, but Bayer had refused. “This is an ideal situation for data sharing,” he said. “The evaluation of the data in this trial should not go behind the curtain. And it seems imprudent to allow those who conducted the trial to be the only ones who can touch the data.”