Clinical Trial GCP Failures Spark FDA Warning Letter

March 11, 2010

FDA issued a new Warning Letter for the most common GCP failures: Informed consent; recordkeeping; and protocol adherence. The 24 February letter to a clinical investigator in Meridian, MS is a textbook case on how not to conduct a clinical trial. First, the investigator failed to recruit eligible subjects and it went downhill from there. This was not a case of Good Clinical Practice (GCP).

FDA GCP Warning Letter

Study Eligibility is a Major FDA Concern

The problem is that this is a psychiatric study and the subjects need to be diagnosed with bipolar disorder in order to participate. Protecting research subjects who may have diminished autonomy is a primary concern for FDA. Thee of six subjects randomized in the study did not meeting the eligibility criteria of having Bipolar I Disorder. FDA considers this “placed at risk for injury from participation in the study,” a serious GCP violation.

FDA has paid closer attention to meeting eligibility requirements of a protocol listed in the inclusion/exclusion criteria. It has been showing up on more Warning Letters in the past two years. And the problems continued from there. One subject was dosed three days before baseline. Not good.

Recordkeeping Errors:

FDA cited the investigator for numerous recordkeeping errors noting:

The records for Subject 1004 contained numerous errors in subject number, protocol number, and date or identity of study visit. For example:

i. Numerous records reflect that subject number 1002 was used instead of the correct subject number 1004.

ii. Forms marked “Screening Visit,” “Week 1 Visit,” and “Week 4 Visit” all are dated October 31, 2006.

iii. There are two forms marked “Week 1 Visit” documenting the Children’s Depression Rating Scale Revised (CDRS-R) evaluation with two different dates, October 31, 2006 and November 8, 2006.

Informed Consent:

FDA Clinical Trial

FDA Approval Requires Sound Data

The Warning Letter goes on to list informed consent violations and failure to inform the IRB of changes in research activity, something I believe you will be seeing more of. None of these violations involve fraud, the topic in the previous two posts. However, they seriously jeopardize the quality of the research data and fully deserve FDA’s attention. The Division of Scientific Investigations (DSI) in the Center for Drug Evaluation & Research issued the Warning Letter.

Read the Warning Letter here:



Special Notice: The Blog was published in the Journal of Diabetes Science & Technology on the topic of Supervisory Responsibilities of Investigators with my colleagues Ann Berenbaum and Patti Young.

Access the Abstract Here


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