Regulatory Focus™ > News Articles > FDA Blasts Clinical Investigation in Warning Letter, Saying Deviations Impacted Study Validity, Inte

FDA Blasts Clinical Investigation in Warning Letter, Saying Deviations Impacted Study Validity, Integrity

Posted 03 September 2013 | By Alexander Gaffney, RAC

Failure to follow the agreed-upon protocol for a clinical trial for an investigational pain pill product has earned a clinical investigator a Warning Letter from the US Food and Drug Administration (FDA), the agency has announced.

Deviating from Protocols

The letter to Henry Frazer of Montgomery, AL-based Drug Research and Analysis Corporation said FDA investigators had observed "objectionable conditions" during a Bioresearch Monitoring (BIMO) program checkup on Frazer's site, which was in the process of investigating two separate drug products, the name and manufacturers of which have been left redacted by FDA in its letter.

The core of FDA's complaint strikes at the heart of what clinical investigators are supposed to ensure: that the trial adheres to the sponsor and Investigational Review Board (IRB) agreed-upon trial design and protocols. However, FDA's inspection determined a number of lapses with respect to this obligation.

In one case, FDA alleged that a patient had not been given the agreed-upon tool to assess his/her own level of pain, and that the study coordinator had instead "used the subject's login code and entered the subject's pain assessment scores … when the subject was unable to provide a pain score."

Then, after the subject had undergone a surgical procedure to reduce their pain, the patient was "sedated and was unable to participate in the evaluation of [his or her] pain," FDA recounted.

This practice was reportedly duplicated across multiple patients-at least five, by FDA's count.

"By failing to ensure that pain-assessment data were entered only by the subjects, as required by the protocol, you compromised the validity and integrity of data collected at your site," FDA charged.

Patient Criteria Ignored

But the trial site failed to uphold other, critical aspects of the protocol as well, FDA purported. In one case, a patient who had failed to qualify for the trial as a result of having a QTc interval longer than 450 milliseconds was enrolled despite the noted limitation. That subject's heart condition marked a "constant threat to life," and could have placed the subject at added risk of adverse events during the trial, FDA added.

In another incident, FDA noted that while the protocol prohibited the use of either Percocet or Oxycontin during the duration of the trial, two subjects had both "received multiple doses" of the respective drugs.

"Your failure to prevent the administration and use of prohibited pain medications during the study compromised data integrity by prohibiting an evaluation of the therapeutic benefit of the study drug alone," FDA said.

FDA said it is still seeking more information on how the violations might have-or might not have-impacted the validity of study data, but said the deviations from the protocol had already served to compromise the "validity and integrity of data captured" at the study site.

FDA Warning Letter to Frazer


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