FDA’s new guidance on monitoring clinical trials strongly encourages taking a risk-based approach
Arisk-based approach to monitoring clinical trials: It’s the way to go now.
That was the thrust of the draft guidance just released by the FDA, as well the key finding of the first study, published earlier this summer, by the Clinical Trials Transformation Initiative (CTTI), a group founded by the FDA and Duke University Medical Center to identify ways to improve the quality and efficiency of clinical trials. The EMA also recently touched on the need for risk-based trial management in a reflection paper saying current GCP rules need an update.
The FDA, in its draft guidance published Aug. 24 and titled “Guidance for Industry Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring,” said advances in technology should allow sponsors to handle much of trial monitoring electronically rather than having to physically send monitors to each investigative site every four to eight weeks, the current common practice. Those sites that need more attention in order to keep quality high should continue to receive that attention, and those that don’t should be monitored from a distance and visited less frequently, said the FDA.
“FDA encourages greater reliance on centralized monitoring practices than has been the case historically, with correspondingly less emphasis on on-site monitoring,” said the guidance, adding that the extent to which centralized monitoring practices can be employed will depend on accessibility of electronic records and electronic data capture (EDC) systems.
The FDA had never stated exactly how it wanted monitoring handled, leading the commercial drug industry to drift toward a cover-all-your-bases approach. That translated into monitors visiting every site approximately every six weeks and going through all of the data, said Judith Kramer, executive director of CTTI. This has been going on since the 1980s and is both exhausting and expensive, she added.
Now, with the new guidance, sponsors have a more solid idea of what the FDA expects and is comfortable with in the realm of monitoring. Another upside: A greater reliance on a more centralized, technology-based approach should save the industry millions of dollars each year in on-site monitoring, which is said to be one of the most expensive components of clinical research.
The guidance encourages those performing trials to drop the common, one-size-fits-all approach to monitoring and instead come up with a tailored monitoring plan for each trial.
“No single approach to monitoring is appropriate or necessary for every clinical trial,” said the guidance. “FDA recommends that each sponsor design a monitoring plan that is tailored to the specific human subject protection and data integrity risks of the trial. Ordinarily, such a risk-based plan would include a mix of centralized and on-site monitoring practices. The monitoring plan should identify the various methods intended to be used and the rationale for their use.”
The FDA recently withdrew its 23-year-old guidance on monitoring, which stated that the “most effective way” to monitor an investigation was to “maintain personal contact between the monitor and the investigator throughout the clinical investigation.” Said the FDA in its new guidance on monitoring: “At the time... sponsors had only limited ways to effect meaningful communication with investigators other than through on-site visits.”