Clinical trial monitoring – the present and the future

March 11, 2015 | By Márcio Barra

 

(Note: all references used are in the comments)

The modern clinical trial is a significant undertaking, and one that requires a multidisciplinary team(1). The current research team includes the principal investigator, sub – investigators, data managers, statisticians, clinical research coordinators (CRC), and the monitor or clinical research associate (CRA).

The International Conference on Harmonization (ICH) E6 Good Clinical Practices guidelines defines monitoring as “The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s)”. CRAs are responsible for monitoring the trial, a task which ensures the integrity of the data that is being collected. It also allows the sponsor to closely follow the study centres, evaluate their conduct, and identify bottlenecks in patient recruitment(3).

In the past, it was the sponsor that would send their personnel to research sites to carry out the monitoring activities. This changed in the early nineties, with the emergence of contract research organizations (CROs). Like many other aspects of trial conduction, monitoring began to be outsourced (4).

The ICH guidelines state that data should be accurate, complete, legible, and timely. However, they do not provide instructions on how to approach data monitoring or individualized approaches for different types of trials. This leaves room for the industry to experiment with different strategies for trial monitoring, and with the advent of EDC, news ways to monitor clinical trial data are becoming more and more common.

On-Site Monitoring

On-site monitoring is the current industry standard, and one that has stuck with clinical trials for some decades (6). Here, the CRA is assigned to monitor a clinical trial or an observational study in a study centre or group of study centres, and then carries an in-person site evaluation (6). The most significant activities carried out by a CRA include: (1) the study initiation visit, where the CRA visits the centre to prepare the study staff for conducting the study; (2) several monitoring visits to a centre during the course of the trial; and (3) the study closure visit.