FDA urges remote monitoring of clinical trials
As technology makes the world smaller, monitoring clinical trials no longer requires traveling to a destination to check up on the investigators. Much of this work can be done remotely and the FDA, in fact, wants to encourage sponsors to undertake more of what the agency calls risk-based monitoring in order to match international standards articulated by the International Conference on Harmonisation.
And so the agency has just issued new guidance for drugmakers and contract research organizations, or CROs, to help sort out the variables that would determine when centralized monitoring would be preferable over on-site monitoring. The primary focus, the FDA notes, should be on steps that protect human subjects, while maintaining data integrity and compliance with regulations.
Despite advances in data gathering and the expense associated with travel, frequent visits to each clinical investigator site remains the predominant method for evaluating study conduct and reviewing data for each enrolled subject. Why?
For major efficacy trials, drugmakers typically conduct on-site monitoring visits at approximately four- to eight-week intervals. The reason is a perception that frequent visits, which presumably yield 100 percent verification of all data, is the method preferred by the agency.
However, the FDA notes academic centers, cooperative groups, and government organizations use on-site monitoring less extensively. For example, some government agencies and oncology cooperative groups typically visit sites only once every two or three years to qualify or certify study sites to ensure resources, training and safeguards are in place to conduct clinical trials, the FDA writes.
The agency also notes that data from critical outcome studies, such as some trials sponsored by the National Institutes of Health, the Medical Research Council in the UK, have not had regular on-site monitoring and relied largely on centralized or other alternative monitoring methods. This underscores the reality that centralized monitoring can and should be considered, according to the FDA.
To make its case, the FDA points to publications that suggested various problems with data, such as fraud and fabrication, may be more readily detected by centralized monitoring techniques than by on-site monitoring. And, of course, the growing use of electronic data capture, or EDC systems increasingly make it possible to accomplish this goal and less reliance on on-site monitoring.
Specifically, the FDA suggests that centralized monitoring should be used to not only replace or augment on-site monitoring, but also for identifying higher risk clinical sites, such as those with data anomalies or a higher frequency of errors, protocol violations, or dropouts relative to other sites. This approach should also be used to verify source data remotely, conduct aggregate statistical analyses of study data, conduct analyses of site characteristics.
However, if a drugmaker or CRO intends to rely heavily on centralized monitoring practices, they should still consider conducting at least one on-site monitoring visit per site, preferably early stages of a study, to evaluate processes and controls for handling data and source documents, particularly for trials intended to support marketing applications, the FDA suggests.
But when exactly would more on-site monitoring be warranted?
Sites in geographic areas where there are differences in standards of medical practice, subject demographics or less established trial infrastructures may require more intensive monitoring. Similarly, a study that involves a population that is seriously ill or vulnerable in order to ensure appropriate protection is being provided.
Another reason would be investigators, because some may lack significant experience in conducting and overseeing investigations, using a novel or innovative medical device or they may benefit when conducting certain surgical procedure associated with medical devices.
And the FDA goes on to say that on-site monitoring would be useful for trials where there are significant safety concerns with a product or for which there is no prior experience in human clinical trials, such as a Phase One trial or a device feasibility study.
You can read the guidance here.
By Ed Silverman
Pharmalot
http://www.pharmalot.com/2011/09/fda-urges-remote-monitoring-of-clinical-trials/
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