On 2017 Apr 21, Vera Sharav commented:

A warning to doctors who have relied on the claimed safety and efficacy of rivaroxaban (trade name Xarelto) based on reports about the RECORD trials such as this one, published in The Lancet.

Please read “C. Seife. Research Misconduct Identified by the US Food and Drug Administration: Out of Sight, Out of Mind, Out of the Peer-Reviewed LiteratureJAMA Internal Medicine, April 2015.” The JAMA report identified the Lancet report as failing to disclose that the FDA inspections had found serious violations at 8 of the 16 sites at which the RECORD 4 trial was conducted. The violations, including “systemic discarding of medical records, falsification, improprieties in randomization,” were so serious that “the entire study, RECORD 4 […] was deemed unreliable by the FDA.”

Among the findings by the FDA Compliance Review: Xarelto (rivaroxaban), May 24, 2011, include: "violation of good clinical practice including prospective randomization, falsification, missing records…Although issues with clinical trial monitoring inadequacies were present in all four RECORD trials, the deficiencies were most frequent in RECORD 4.”

FDA cites unreported serious adverse events (SAEs) “defined by the necessity of expeditious medical evaluation or involving bleeding or hepatic events."

“There were 8 unreported SAEs noted in the audits, all in RECORD 4. When the unreported AEs were individually examined for significance as defined by the necessity for expeditious medical evaluation, or were AEs involving bleeding or hepatic events, there were 16 in RECORD 1, 24 in RECORD 2, and 265 in RECORD 4; RECORD 3 could not be tabulated due to failure to list individual laboratory abnormalities.

During the data verification process of RECORD 4, 504 unreported AEs were noted, as were 28 previously unreported SAEs. The audits identified more than twice as many AEs in RECORD 4 than in the other RECORD studies, and all of the unreported AEs were from RECORD 4”.

Seife reported that of the 78 publications that resulted from trials in which the FDA found significant violation – only 3 (4%) – mentioned the violations or serious objectionable practices found during the inspection. “No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.”

A retraction of this grossly misleading report by AG Turpie & 171 collaborators is long overdue.

Vera Sharav President, Alliance for Human Research Protection www.ahrp.org veracare@ahrp.org

On 2017 Apr 21, Vera Sharav commented:

A warning to doctors who have relied on the claimed safety and efficacy of rivaroxaban (trade name Xarelto) based on reports about the RECORD trials such as this one, published in The Lancet.

Please read “C. Seife. Research Misconduct Identified by the US Food and Drug Administration: Out of Sight, Out of Mind, Out of the Peer-Reviewed LiteratureJAMA Internal Medicine, April 2015.” The JAMA report identified the Lancet report as failing to disclose that the FDA inspections had found serious violations at 8 of the 16 sites at which the RECORD 4 trial was conducted. The violations, including “systemic discarding of medical records, falsification, improprieties in randomization,” were so serious that “the entire study, RECORD 4 […] was deemed unreliable by the FDA.”

Among the findings by the FDA Compliance Review: Xarelto (rivaroxaban), May 24, 2011, include: "violation of good clinical practice including prospective randomization, falsification, missing records…Although issues with clinical trial monitoring inadequacies were present in all four RECORD trials, the deficiencies were most frequent in RECORD 4.”

FDA cites unreported serious adverse events (SAEs) “defined by the necessity of expeditious medical evaluation or involving bleeding or hepatic events."

“There were 8 unreported SAEs noted in the audits, all in RECORD 4. When the unreported AEs were individually examined for significance as defined by the necessity for expeditious medical evaluation, or were AEs involving bleeding or hepatic events, there were 16 in RECORD 1, 24 in RECORD 2, and 265 in RECORD 4; RECORD 3 could not be tabulated due to failure to list individual laboratory abnormalities.

During the data verification process of RECORD 4, 504 unreported AEs were noted, as were 28 previously unreported SAEs. The audits identified more than twice as many AEs in RECORD 4 than in the other RECORD studies, and all of the unreported AEs were from RECORD 4”.

Seife reported that of the 78 publications that resulted from trials in which the FDA found significant violation – only 3 (4%) – mentioned the violations or serious objectionable practices found during the inspection. “No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.”

A retraction of this grossly misleading report by AG Turpie & 171 collaborators is long overdue.

Vera Sharav President, Alliance for Human Research Protection www.ahrp.org veracare@ahrp.org