Audits, Monitoring, and Inspections Flashcards

Which ICH E6(R2) principle specifically addresses the need for a systematic, independent examination of trial-related activities to evaluate whether they were conducted according to the protocol?

Answer: Audit

ICH E6(R2) defines an audit as a systematic, independent examination to determine whether trial activities comply with the protocol, SOPs, GCP, and regulatory requirements.

A sponsor is implementing Risk-Based Monitoring (RBM). Which factor would MOST likely increase the frequency of on-site monitoring for a particular site?

Answer: The site has a high rate of protocol deviations and late adverse event reporting

High protocol deviation rates and late SAE reporting are risk signals that indicate the site needs more intensive on-site oversight.

During source data verification (SDV), the CRA finds that a lab value recorded in the CRF is different from the value in the laboratory report. This is an example of:

Answer: A data discrepancy requiring a query

A transcription error between source data and the CRF is a data discrepancy that should be resolved through the query process.

When an FDA inspector issues a Form FDA 483, what does this document represent?

Answer: Inspectional observations of conditions that may constitute violations

FDA 483 lists observations of conditions the inspector believes may violate regulations; it is not a final agency determination and gives the inspected party an opportunity to respond.

A CRA is conducting centralized (remote) monitoring and notices that a site has an unusually low screen failure rate compared to all other sites. This pattern should trigger:

Answer: A risk signal investigation that may prompt a for-cause audit

Outlier patterns in key metrics like screen failure rates can indicate data fabrication or inappropriate enrollment, warranting further investigation and potentially a for-cause audit.

According to ICH E6(R2), the sponsor's audit function must be independent of:

Answer: Clinical monitoring and trial management

ICH E6(R2) requires that auditors be independent of clinical monitoring and trial management to provide an objective assessment of quality.

What is 'source data' as defined under ICH E6(R2)?

Answer: All information in original records and certified copies used to reconstruct and evaluate the trial

Source data includes all original records (paper or electronic) and certified copies from which CRF data are derived, enabling reconstruction and evaluation of the trial.