LETTER

Year : 2010  |  Volume : 1  |  Issue : 3  |  Page : 113

Insights from FDA Warning Letters

Correspondence Address:

Source of Support: None, Conflict of Interest: None

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Sponsor/CRO

• Failure to ensure proper monitoring of the investigation
• Study monitors failed to ensure that the investigation was conducted in accordance with the investigational plan
• Study monitors failed to identify that no physical examination, assessment, or overall clinical assessment was documented in study source documents or on the Case Report Form
• Study monitors failed to identify discrepancies in study records related to observations and data pertinent to the investigation
• Study monitors failed to identify that study documents contained conflicting information regarding accountability of the drug
• Study monitors failed to identify that subjects who did not meet eligibility criteria were enrolled
• Failure to ensure that the investigations were conducted in accordance with the general investigational plan and protocols contained in the IND
• Insufficient documentation to assess that the sites had physician qualified to read and interpret the pediatric ECGs
• Subjects at multiple sites were not given the correct doses
• Failure keep each participating investigator informed of new observations discovered by or reported to the sponsor on the drug, particularly with respect to adverse effects and safe use

Investigator

• Failure to protect the rights, safety, and welfare of subjects under your care
• Failure to personally conduct or adequately supervise the trial
• Failure to conduct the study in accordance with the investigational plan
• Failure to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation
• Failure to promptly report to the sponsor any adverse effect that may reasonably be regarded as caused by, or probably caused by, the drug
• Failure to promptly report to the IRB all unanticipated problems involving risk to human subjects
• Submission of false information to the sponsor in a required report
• Failure to maintain adequate records of the disposition of the drug, including dates, quantity and use by subjects
• Permitted an individual with no medical training to evaluate laboratory results for clinical significance
• Failure to retain records that record all observations and other data pertinent to the investigation, such as case report forms, progress notes of the physician, and nurses' notes, for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated

Institutional Review Board

• Failure to prepare, maintain, and follow written procedures for conducting its initial and continuing review of research
• Approval without determining that the following criteria were met: that risks to subjects were minimized and risks to subjects were reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result
• Failure to conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once per year.
• Failure to prepare and maintain the minutes of IRB meetings in sufficient detail to show attendance at the meetings; actions taken by the IRB; the vote on these actions including the number of members voting for, against, and abstaining; the basis for requiring changes in or disapproving research; and a written summary of the discussion of controversial issues and their resolution
• Failure to adopt a method for keeping all members advised of research proposals which have been approved under an expedited review procedure
• Failure to ensure that no IRB member participates in the initial or continuing review of any projects in which the member has a conflict of interest
• Failure to prepare and maintain adequate documentation of IRB activities, including a list of IRB members identified by name; earned degrees; representative capacity; indications of experience; and any employment or other relationship between each member and the institution.
• Failure to maintain copies of all research proposals reviewed, scientific evaluations, if any, that accompany the proposals, approved sample consent documents, progress reports submitted by investigators and reports of injuries to subjects, and correspondence with investigators