Zachary Brennan from RAPS Regulatory Focus reports the FDA has significant concerns about Novartis clinical data practices during a recent clinical inspection.
As part of the FDA’s review of Novartis’ new drug application for Mayzent (siponimod) the regulatory questioned the industry sponsor’s data practices during a clinical inspection. Apparently, the FDA noted “During the sponsor inspection, significant data reliability concerns were identified.”
The FDA noted in one study protocol the blinding “was not adequately maintained as specified in the protocol throughout the course of the trial at 62 (21%) of 294 sites. Study personnel were given inappropriate access to the first dose and main databases affected 295 (17%) out of 1651 total study subjects.”
Novartis did not follow good practice by using two databases to track user activities. The necessary requirement to track user activity, such as which users accessed databases and when, as well as what data was viewed, was inherently limited due to lack of a centralized system for audit trail access, etc.
Moreover Mr. Brennan reported the FDA also charged “Novartis did not have sufficient procedures outlined in their monitoring plan for granting and revoking access as well as detecting inappropriate access to databases that contained study information that could be potentially unbinding. Novartis CRA did not properly grant study personnel (e.g. study coordinators, investigators, and EDSS raters) access to the databases used in the trial. In addition, the CRAs failed to identify cases where inappropriate database access was granted to site personnel.”
Brennan states the FDA couldn’t conclude the inappropriate access to some information led to bias. But the agency couldn’t’ rule bias out in terms of study data reliability.
RAPS reports in December 2018, Novartis was requested to undertake a sensitivity analysis, “excluding in the per-protocol analysis subjects who may have been impacted, including 62 subjects who were potentially affected by the 11 EDSS raters who had inappropriate access to the first dose or main databases and 101 subjects who were potentially affected by the 32 users of the main database who had inappropriate access to the first dose database.” Apparently, Novartis did not respond to a request for comment.
Follow the link to review more information concerning the FDA critique of Novartis data management and clinical quality issues.Source: Raps