Repeated violations leading to warning letter in a paediatric clinical trial

Human beings make mistakes regardless of their experience, intelligence, motivation or vigilance. Some people say that error is the inevitable downside of having a brain! One definition of “human error” is “human nature”. In another words, it is impossible not to make error  when conducting a clinical trial. However, we should have a safe system and process to minimize the level of errors. Errors in critical processes or data should be avoided, as they have serious consequences for the patient safety and trial data, which might jeopardise the whole trial.

During inspection, the inspectors often examine trials with an aim to evaluate compliance of conduct with protocol and regulations/guidelines. Inspectors principally review the data submitted along with application to the regulators and check the data generated during the trial. Therefore, documentation holds a critical link in assessing trial quality. Poor and inadequate documentations fail to assure quality of data and patient safety/welfare; leading to serious inspection findings.

Warning letters or critical finding are often issued whenever there are regulatory and GCP violations that are repeated and/or involve submission of false information to the authority.

Below are highlights from a recent warning letter from FDA to an investigator in a paediatric clinical trial. This warning letter demonstrated how important it is to follow the protocol and informed consent procedure and to handle the records correctly.

• Failing to obtain informed consent of the subject’s legally authorized representative prior to involving the children in research.
• Enrolling subjects even the subjects met the exclusion criteria.

Note: questions about any aspect of the protocol, especially in/exclusion criteria should always be clarified and agreed with the sponsor or its designee.

• Enrolling subjects although the subjects were using prohibited medications according to the protocol.
• Failing to follow the treatment guideline as described in the protocol.
• The study drug (investigational medicinal product), which was exposed to temperature deviation, was administered to the subject before the product was released for use by the sponsor.
• Failing to have or document follow-up phone calls for many subjects.
• Discrepancies between the source documents and case report forms (CRFs) or no source document available.
• Systematic change of the same data point for several subjects without providing a reasonable explanation but only entry error.

Reference to the full warning letter:

https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm623054.htm

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