Nearly 7 months since the FDA approved the blockbuster candidate Eliquis, media reports have shed light on data errors and a case of alleged fraud from clinical trial sites in China. The revelations in reports from Elsevier and Bloomberg could further harm the image of China as a hotspot for clinical development.
The FDA found out about data irregularities prior to denying approval of Bristol-Myers Squibb ($BMY) and Pfizer's ($PFE) Eliquis in a June 2012 complete response letter. Prior to the rejection, Bristol told the agency that some patients got the wrong medicine, records were changed on the sly and serious adverse reactions were missing, Bloomberg's Drew Armstrong noted. As Elsevier's Pharmaceutical Approvals Monthly first reported, concerns about the integrity of the data contributed to the 9-month delay in the FDA's approval, which came in December.
There are several troubling issues exposed in the articles. One is whether the alleged fraud in the Eliquis study in China marks an isolated case or a pattern of misconduct in drug research in the country with the world's largest population. This story comes fast on the heels of GlaxoSmithKline ($GSK) firing its head of R&D in Shanghai after allegations of unscrupulous treatment of pre-clinical study data, prompting the company to slam the brakes on an early-stage human trial.
Bloomberg's article also highlights how the FDA cleared the death benefit on Eliquis' label over the objections of Thomas Marciniak after his independent review of the trial data. And, of course, the agency cleared the therapy, which is an alternative to generic warfarin, without the public's knowledge about its deep concerns about the data irregularities in China.
Take a whiff of this snippet from one of the documents posted on the FDA's website:
"Although fraud at Site 1200 in China was well documented, there was no evidence that fraudulent activity occurred elsewhere. OSI [FDA's Office of Scientific Investigations] recommended that data from 24 sites in China be excluded because they could not provide inspectional evidence to support data integrity and subject safety, given that the Ms. [name redacted] and Mr. [name redacted] worked at these sites. The remaining inspections of clinical investigators, CRO, and applicant did not reveal systemic evidence of inadequate monitoring or data integrity issues. No regulatory violations were identified during the PPD inspection; and minor regulatory violations found during the applicant inspections. OSI recommended that the data submitted by Bristol-Myers Squibb may be used in support of the respective indication."
This shows that the FDA's inspection clearly found problems with two workers involved in Chinese sites of the study. It largely exonerates the sponsor and CRO. As Bloomberg reported, Bristol fired culprits in the misconduct found in the trial. Still, investors and the public were kept in the dark about these issues when the complete response letter was announced last June and later in the review process.
- check out Bloomberg's article
- and the story from Elsevier
- and the trove of FDA documents