Noncompliance with Randomized Blinded Treatment using IRT - Investigator Warning Letter

01/03/2023

Interactive Response Technology (IRT) is an electronic system commonly used to manage investigational product (IP) supply and to randomize study participants while maintaining the blind, thus reducing bias and balancing enrollment into the treatment arms. Qualified site staff use the IRT to randomize doses according to protocol, and often the IRT will trigger an automatic refill when supply is low.

An investigator was recently issued a warning letter due to noncompliance with the IRT, which can impact the safety of the participants and the quality and integrity of the data. Per protocol, IP was to be administered according to hemoglobin levels and the IRT was to randomize the doses appropriately.

Observations that the FDA field investigator found were:

  • Coordinators ordered IP kits rather than using the IRT

  • IRT transactions to obtain randomized doses were not completed

  • IP was not administered per protocol

  • Participants missed multiple doses, sometimes with long periods of consecutive days

    • One participant who missed 43 doses was hospitalized to receive blood product

  • IP was administered when it should have been held

  • IP was held when it should have been administered

  • IP was administered at the full dose rather than the reduced dose

There was inadequate investigator oversight of the delegated site staff and study procedures evidenced by the investigator’s statement that they were not aware of the issues until a year after the multiple missed doses. The investigator also stated the nurses informed them about the lack of IP available at the site and the investigator managed the issue by texting the coordinator, while not indicating that any follow up for resolution or other oversight occurred. The FDA notes that the corrective action provided in the written response did not adequately describe how the investigator will comply with protocol and IRT procedures to prevent further issues. The neglect to use the IRT to generate randomized doses, lack of appropriate protocol required dose adjustments, and missed doses due to lack of IP supply adversely impacts participant safety and data quality.

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-The Clinical Pathways Team

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