Good Clinical Practice: A Question & Answer Reference Guide - May 2018 - 48

GCP: A Question & Answer Reference Guide
make certain that based on the subject's clinical history, the subject was appropriate for the study. You stated that
you counted on the study coordinators to make sure that the source data adequately represented and documented
this information. You further stated that you clearly should have looked at the records yourself to ensure that
they had been done appropriately. Your statement that you counted on the coordinators to be sure that the source
data adequately represented and documented this information is unacceptable. As the clinical investigator, it is
your ultimate responsibility to ensure that the study was conducted according to the requirements set forth in the
investigational plan."
In an October 2010 warning letter, the agency stated that, "after the... IRB learned that your April 2, 2009
Research Site Submission Form was inaccurate, it withdrew its approval for Protocol... and denied your application
for approval to conduct a second proposed clinical study. In an August 7, 2009 letter to the... IRB [asking that
the board reconsider], you stated that a study coordinator completed the April 2, 2009 Research Site Submission
Form and completed questions 29(d) and 29(e) without your input. However, by signing the April 29, 2009
'Research Site Submission Form,' you certified that you 'ha[d] reviewed all responses provided in this 'Research
Site Submission Form' and that all responses are true and accurate' (emphasis in original). Therefore, the fact that
a study coordinator completed the form did not relieve you of your responsibility for ensuring its accuracy before
you signed it."
In a June 2009 warning letter, CDER noted that a clinical investigator's "supervision of personnel to whom [he]
delegated study tasks was not adequate," and that the investigator "had little involvement in this study." The trial
staff list indicated that the study site's two clinical research coordinators were delegated several responsibilities,
including the affirmation of inclusion/exclusion criteria, and the assessment of adverse events, serious adverse
events, and study endpoints. While the investigator later told the FDA that he was "inexperienced in conducting
trials" and therefore "relied on [my] clinical research coordinators to conduct the study and complete the study's
paperwork," the agency's review found that "the resumes of... the primary study coordinators [indicated that
they] did not appear to be qualified, certified, or significantly medically trained and licensed to be independently
making judgments related to determination of eligibility of subjects for enrollment into the study and/or making the
determination as to whether or not adverse events were related to the use of the investigational drug."
A November 2009 warning letter cited a clinical investigator for inadequate study supervision after the agency
found that the investigator had pre-signed "multiple blank source document worksheets" for several study subjects.
"Your signature on a document indicates that you have reviewed the data within; thus, source documents should
not be signed until relevant data has been added and reviewed."
In one case, the FDA determined that an investigator had failed to adequately supervise a study because a
study monitor could find no investigator notes on any patients enrolled in a study, even during a several-month
period following a monitor's discovery and notification of numerous protocol deviations/violations at the site.
"This timeline shows that as an investigator, you failed to have adequate involvement and oversight over this study
during the study," the FDA warning letter noted.
In the other case, an FDA warning letter stated that the investigator "had little personal involvement in the
conduct of the study beyond referring patients from [his/her] practice for enrollment in the study, conducting
physical examinations, and reviewing screening ECGs, and that [he/she] failed to adequately supervise individuals
who performed study tasks." Specific citations were made for the following:
* Although the protocol required that the investigator review all available assessments at the screening/baseline
visit (e.g., vital signs, current medications, concomitant medical conditions, inclusion/exclusion criteria) to
ensure subject eligibility for the study, investigator and study staff statements during the FDA site inspection
indicated that the study coordinator screened and enrolled study subjects. The study records do not reflect that
the investigator reviewed the subject screening assessments and related subject assessments consistent with
the protocol. Further, since there was no CV for the study coordinator, it was not clear if she was qualified
to perform such duties, the FDA stated. The study coordinator enrolled "multiple subjects" who were not
eligible for the study.
* Available study documentation indicates that the results of key laboratory testing (e.g., end-of-study safety
labels, screening safety labs) for multiple subjects may have been evaluated only by a sub-investigator who
lacked medical training. "You permitted an individual with no medical training... to evaluate laboratory

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Table of Contents for the Digital Edition of Good Clinical Practice: A Question & Answer Reference Guide - May 2018
