The monitoring of clinical studies is extremely important to protect the rights, welfare and safety of the study participants, and to assure the integrity of the study data submitted to the FDA and thus, ultimately the accuracy of FDA’s evaluation of submitted studies and subsequent approval decisions.  If you have been following the debarment notifications in the Federal Register over the past year or so, most of the people being debarred have been either clinical investigators or staff associated with the conduct of clinical trials on behalf of pharmaceutical company sponsors. Some issues that have led to convictions which in turn resulted in debarment, include but at not limited to, falsification of case histories, recording visits that have never taken place, failing to disqualify a subject from a study when not meeting inclusion criteria, reporting false laboratory results, lying to FDA investigators, and on and on.

The FDA says the Q&A guidance document entitled, A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers (here) “expands on the guidance for industry Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring (August 2013) (the 2013 RBM guidance)  by providing additional information to facilitate sponsors’ implementation of risk-based monitoring.”

The document provides responses to the following eight (8) questions that cover monitoring approach, monitoring plan content, and follow-up communications of monitoring results:

Q1. What is the purpose of the risk assessment and should sponsors document their methodologies and activities for assessing risk?

Q2. Should sponsors monitor only risks that are important and identified during their initial risk assessment as likely to occur?

Q3. What factors should sponsors consider when determining the timing, types, frequency, and extent of monitoring activities?

Q4. How can a risk-based approach to monitoring that includes centralized monitoring help minimize missing data or protocol deviations?

Q5. Should the risk-based monitoring approach include processes to ensure that appropriate blinding is maintained?

Q6. What elements should sponsors include in monitoring plans?

Q7. How should sponsors follow up on significant issues identified through monitoring, including communication of such issues?

Q8. How should monitoring activities and the results of these activities be documented and shared with those involved in the investigation?

We can not overestimate the importance of clinical study monitoring as one individual can have the capacity to invalidate an entire study if they have a mind to cheat. The cost to industry in terms of potentially having to repeat a clinical investigation or in the delay of obtaining FDA approval could have a devastating impact on the project. Not to mention the harm that could befall patients if the drug is erroneously approved on bad or fraudulent data.