Analysis of FDA Warning Letters Shows Patient Safety Violations, Inadequate Record Keeping Common in Clinical Trial Concerns

Study of FDA warning letters over the last 7 years discovers that patient safety violations and poor record maintaining are common clinical trial issues.In the US, study involving human participants is regulated by federal regulations enforced by the FDA. The FDA’s Bioresearch Monitoring Program was set up to secure the rights, well-being and safety of human subjects and protect the reliability of data pertaining to trials featuring human participants.

The FDA has the power to access, copy and validate any records created by the clinical investigator. Also, the FDA performs site visits to clinical investigators, sponsors, monitors, CROs, animal labs and bioequivalence analytical labs.

Generally, this happens:

• If there is a complaint about the conduct of a study
• In response to sponsor issues
• On cancellations of the clinical site
• To offer real-time assessment of the conduct of the trial and the safety of the trial participants
• On request by the FDA review department
• In relationship with investigational products “of greater importance.”

When the FDA discovers that offenses of significant regulations have took place, they provide warning letters to encourage voluntary compliance and corrective action prior to any enforcement is began.

With respect to the FDA, a warning letter is “a casual advisory to a organisation communicating the Agency’s position on a issue but does not commit the FDA to taking enforcement action.”

Study reviews 84 initial warning letters given during the period 2005-2012

To analyze the level of the violations being picked up and corresponded to clinical investigators, the authors of the new study analyzed the content of 84 initial warning letters issued by the FDA to 46 trial sponsors, 20 lead scientists and 18 IRBs during 2005-2012.

The study reveals that the very generally raised issue from clinical trial sponsors is a inability to monitor progress with respect to the state schedule, followed by a failure to get the agreement of the principal investigator. Of these cautions, 3 out of 4 associated to new devices, with a quarter pertaining to new drug research.Of issues raised by the FDA to lead researchers, 95% concerned failing to stick to the stated plan for the research, while 55% concerned to inability to report side effects and safeguard the safety of subject. Around 40% of these warnings related to inadequate record maintaining. Overall, 80% of these warnings relevant to drug trials.

The most frequent warnings for institutional boards, meanwhile, associated to failures to follow SOPs and poor record keeping.Evaluating their outcomes – which are presented in the Journal of Medical Ethics – with a past analysis from 1997, the scientists identified that while regulatory compliance has enhanced, supervision has gotten worse.Also, the scientists identified that two new serious offenses have become an issue since the 1997 analysis. These are unable to get research green-lit by an institutional board prior to commencing the research, and submitting fake data to the FDA and/or sponsors.

“Fair and acceptable techniques for handling offenses during clinical studies have to be developed and executed internationally in order to secure human rights, wellness and safety, and to increase awareness of ethical behavior,” say the authors.

They also suggest that every regulatory authority that monitors clinical studies should conduct inspections of participating centers and consistently publish their outcomes. The authors believe these methods may enhance compliance with good practice.