The FDA today released a 538-page briefing document for an advisory panel meeting on Wednesday and Thursday that will reassess a key clinical trial and reconsider the fate of the now-tarnished former blockbuster diabetes drug rosiglitazone (Avandia, GlaxoSmithKline). (Click here for the FDA documents.) As reported last week, the re-adjudication of the RECORD safety trial performed by the Duke Clinical Research Institute (DCRI) confirmed the initial finding of the trial that rosiglitazone was not associated with an increased risk for cardiovascular events.
For the most part, the FDA documents released today express strong support for the DCRI re-adjudication. But one FDA official, Thomas Marciniak, remains highly critical of RECORD and says the trial data and, therefore, the analysis of the data from GSK and DCRI are completely unreliable. All parties agree, however, that the fundamental underlying design flaws of RECORD– in particular, it’s open-label design– mean that data from the trial will never provide definitive assurance about the safety of rosiglitazone.
One FDA reviewer said the DCRI review of the mortality results in RECORD was “well-conceived and comprehensive” and “no stone was left unturned.” But the same reviewer states:
There is no amount of analytical rigor that can compensate for a weak trial design that is exacerbated by elements of poor execution, both of which afflicted RECORD. Its open- label non-inferiority design was simply problematic, especially for ascertainment of non-mortality MACE during trial execution…. Thus, while we agree with the analytical findings of the DCRI mortality re-analysis, we would emphasize that RECORD’s design irreparably hampers its ability to characterize definitively the CV risk of rosiglitazone.
The panel may well accept the findings of the re-adjudication and the FDA analysis. In that case the terrifying specter looming over the FDA and the rest of the medical establishment– that not just rosiglitazone but the entire drug development and approval process was fundamentally flawed and unreliable– will be put to rest, at least for now.
A Bitter Feud
Buried in the massive document is a bitter feud between an FDA rebel, Thomas Marciniak, and his bosses and other senior officials in the FDA’s drug division….