And despite the FDA action, one or more of those seven flawed studies was used in 22 meta-analyses evaluating Eliquis, Dr. Garmendia found.
In response to the new report, Pfizer and Bristol-Myers Squibb jointly told Reuters Health in an email that “using ARISTOTLE as an example in this analysis is misguided and may confuse prescribers and adversely impact treatment decisions for patients. The falsified data referenced within the JAMA article was isolated to one site, occurred after the completion of the study report and had no impact on the integrity of the results or conclusion of the study.”
(Mr. Seife says in his interview that the problem of falsified data was known before the ARISTOTLE studies were published.)
The Pfizer-BMS statement also says, “The FDA was made aware at the time and conducted their own sensitivity analysis which confirmed no impact from this isolated incident on the ARISTOTLE results. Moreover, a growing body of clinical and real world data have continued to reinforce the efficacy and safety profile of Apixaban.”
“Not all the data within the ARISTOTLE publications were falsified. However, because the researchers knowingly published falsified data, a form of research misconduct, we removed all ARISTOTLE data” when the re-analyses were done, says Dr. Garmendia.
“A lot of the literature that shows a benefit (from prescription drugs) might have to be taken with a grain of salt” based on these findings, says Mr. Seife.
Part of the problem is the FDA itself, as Seife noted in his 2015 paper. The FDA does not typically notify journals when an inspection uncovers problems at a medical center doing the research. Nor does the agency alert the public, and “the documents the agency discloses tend to be heavily redacted. As a result, it is usually very difficult, or even impossible, to determine which published clinical trials are implicated by the FDA’s allegations of research misconduct,” Mr. Seife wrote at the time.
Mr. Seife recommends that “the FDA should make unredacted information about its findings of research misconduct more readily available. The agency should make sure that any substantial evidence of misconduct is available to editors and readers of the scientific literature.”
“It is insufficient for the FDA or another regulatory agency to merely identify research misconduct,” says Dr. Steinbrook. “The study shows that a strategy to fully inform the research community and the public is also needed”
“There’s no system set up to allow medical journals to track this information,” says Dr. Garmendia. “So at the end of the day they’re still relying on the authors to disclose that they have been inspected and if data was thrown out. That just seems to not be taking place, whether it’s because they want a nice clean publication or they don’t want to admit to any mistakes were made.”
