Importance of In-Process Monitoring in Clinical Phases of Bioequivalence Studies

Background

The study protocol required each volunteer to provide a urine sample for Urine Alcohol Testing (UAT) upon Check-In. Only those with a negative UAT result were eligible to enroll in the study.

The objective of this case study is to highlight the critical role of monitoring and the implications of protocol deviations on the integrity of the study results.

Incident Description

During in-process monitoring, the Monitor noticed an unusual pattern: the urine samples from 10-12 consecutive volunteers had an identical color, which was atypical and raised immediate concerns about the authenticity of the samples.

Immediate Action

The Monitor promptly informed the site staff about the observation and requested to inspect the toilet area. The staff were instructed to check for any irregularities from outside the toilet if a volunteer was present, to maintain the participants’ privacy and dignity. Once the site staff confirmed that no one was inside, the Monitor entered the toilet area for verification. Upon inspection, the Monitor discovered a 1000 ml prefilled urine bottle hidden in the toilet area. It became apparent that volunteers were using this shared urine source to fill their containers before submitting them for the UAT. This practice directly violated the study protocol and could potentially lead to the enrollment of ineligible volunteers.

Issue Escalation

The Monitor immediately escalated the issue to the site management. A meeting was held with the site staff, including the Principal Investigator (PI) and the Clinical Research Coordinator (CRC), to discuss the severity of the violation and the potential impact on the study.

Corrective Measures

  • The urine bottle was removed from the toilet.
  • The volunteers involved in the violation were identified, and a repeat UAT was conducted.
  • Additional training was provided to the site staff on proper sample collection procedures.
  • The monitoring frequency was increased to ensure compliance with the protocol moving forward.

Impact on the Study

The unauthorized use of a shared urine bottle posed a significant risk to the study’s integrity. If the issue had not been detected, ineligible volunteers with positive UAT results could have been enrolled, leading to skewed data and potentially invalid study outcomes. The early detection and intervention by the Monitor were crucial in preserving the study’s validity. Upon retesting, 7 out of the 12 volunteers involved in the mishandling tested positive for alcohol in their urine. This confirmed that the original samples were indeed manipulated. These volunteers were subsequently excluded from the study.

This incident underscores the critical role of in-process monitoring in ensuring protocol adherence. Continuous monitoring allows for real-time detection of issues, enabling immediate corrective actions and minimizing the risk of compromised data.

Conclusion

This case study highlights the importance of:

  • Vigilant in-process monitoring during clinical phases to detect and address protocol deviations.
  • Clear communication and swift action when issues are identified.
  • The necessity of strict adherence to protocols to ensure the reliability of bioequivalence study results.