Beginning at 7:30 a.m. Eastern time, the FDA's Medical Imaging Drugs Advisory Committee (MIDAC) will gather feedback and recommendations on whether the FDA should take additional action to regulate the administration of gadolinium contrast. The public is also welcome to contribute during a 75-minute open session from approximately 12:45 p.m. to 2:00 p.m.
The meeting is being held as the FDA faces mounting pressure to act on the gadolinium issue. But the agency is reluctant to move until it sees published literature -- which as of today doesn't exist -- indicating that the retention phenomenon actually represents a health risk to patients.
The gadolinium conundrum
The debate over gadolinium contrast has been underway for years, with Kanda et al detecting higher levels of gadolinium in the dentate nucleus and globus pallidus regions of the brain in patients who received contrast agents. Since then, researchers from around the world have investigated the gadolinium conundrum, such as whether there is less retention with macrocyclic agents.
Most recently, the FDA on May 22 announced that it believes there is no evidence that gadolinium remaining in the body after MRI contrast administration has any negative health effects. The agency's position somewhat conflicts with a March statement from the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) recommending that four linear GBCAs be taken off the market. The PRAC subsequently revised the recommendation to advise that one of the four agents remain on the market for some indications.
In a briefing document for the September 8 meeting, the FDA acknowledged "data gaps" in information about gadolinium retention. In particular, the agency cited several issues that need to be addressed:
- Lack of a clear connection between adverse events that have been reported and extracranial retention
- No clear toxic threshold for retention in the brain or other body organs
- Sparse population-based data in the literature on risk associated with long-term gadolinium retention
"The limited evidence currently available leads [the] FDA to believe that gadolinium brain retention may be a phenomenon without known clinical consequences," it wrote. "However, the human data are sparse and the long-term effects are not known, and more research is necessary."
Thus, the committee has been asked to consider several points:
- Whether there is any clinical significance of gadolinium retention
- How to identify the patient populations in which gadolinium retention may be most significant
- How the agency should approach additional research
- How to inform patients and healthcare providers about potential risks from GBCAs
Given the current limited evidence, the FDA advised that "it is prudent to warn patients and clinicians about gadolinium retention and the related differences among the GBCAs. It could be a factor when weighing the necessity of a GBCA MRI or choosing a specific agent."
Among the participants scheduled to provide comments to MIDAC are Sharon Williams and Hubbs Grimm, the two founding members of the Lighthouse Project, an online resource created to provide information about the potential lingering effects of GBCAs. Both Williams and Grimm continue to battle health problems they believe are related to receiving gadolinium-based contrast.
At the FDA meeting, they plan to discuss their own experiences and present data from postgadolinium injection urine samples voluntarily provided by more than 230 Lighthouse Project members. The investigation showed as much as 500 mcg of gadolinium in urine samples 24 hours after administration and trace levels as long as 10 years after the contrast-enhanced MRI scans.
"Looking closer, we will demonstrate, at least for these people, that gadolinium from contrast MRIs does not clear the body in a few days, a few months, or even many years," Williams and Grimm wrote.
More information about the meeting is available here.
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