Radiologists are facing mounting legal exposure from patients reporting adverse effects from gadolinium-based contrast agents (GBCAs). One expert argued that the industry must step up and take a data-driven approach to paint an accurate picture of contrasts and mitigate their liability risk.
H. Benjamin Harvey, MD, a neuroradiologist at Massachusetts General Hospital in Boston and assistant professor of radiology at Harvard Medical School, said his institution is encountering many cases of gadolinium deposition disease (GDD) each month, making it difficult to ignore.
“Let me be clear from the beginning: Do I think that gadolinium deposition disease is real? Personally, by current data, absolutely not,” Harvey, also a licensed attorney in Massachusetts, said during a Dec. 3 session at the Radiological Society of North America (RSNA) annual meeting. But when discussing litigation and risk-management issues, he believes "we’re not talking about the science completely.”
So what exactly is this disease? It’s been described based on a correlation between a wide variety of vague symptoms and a patient’s exposure to GBCAs during MRI, Nicolas Argy, MD, wrote in an editorial in Radiology Business Journal earlier this year. Those with GDD claim it’s been caused by contrast deposition in tissues within the brain, skin, bone and kidneys. There are five diagnostic criteria for GDD, many of which are subjective and difficult to disprove, Harvey noted.
On this thought, Harvey—who cited no relevant disclosures during his session—said he’s being “battered across the community” for saying it’s “time to take our head out of the sand on this one.”
What does current data show?
GBCAs are considered to have sound safety and benefit-to-risk profiles; the only known disease cases have been tied to nephrogenic systemic fibrosis in patients with impaired renal function. Since that discovery, institutions have tackled the problem through focused screenings and via Food and Drug Administration-mandated black box warnings.
Beyond that, there are “no pathologic-proven consequences to date on gadolinium retention,” Harvey stated in his talk. What’s more, he said, is that the FDA, American College of Radiology (ACR) and American Society of Neuroradiology have echoed this lack of clinical correlation. They have not, however, taken conclusive and official stances on the matter, he noted, with some of these groups, including the ACR, calling for more research on gadolinium.
What doesn’t make sense, Harvey argued, is why European regulators have suspended the use of all Class I GBCAs, or linear agents, which are associated with increased gadolinium retention, without data suggesting pathologic consequences.
So while the majority of data suggests GBCAs are safe, sometimes it only takes one case to flip everything, Harvey said.
The curious case of Roundup
Harvey said the GDD debate is beginning to feel “uncomfortably similar” to lawsuits tying chemical exposure from Roundup herbicide to non-Hodgkin lymphoma.
That litigation had been going on for a long time, but there wasn’t enough data to bring in witnesses to testify until a single meta-analysis without case control studies boosted the correlation between Roundup exposure and lymphoma from 2% to 2.7%, Harvey said.
In July, the number of cases filed against Bayer, which acquired Roundup after its purchase of Monsanto in 2018, sat at around 18,000. According to Harvey and reporting from Reuters, that number is expected to jump to more than 43,000.
Drawing from his experience as an attorney, Harvey noted that the jury and tort system is not purely focused on science, and it only took one meta-analysis to change everything.
“I’m not saying that we’re (radiology) going to get hit. What I’m saying is there’s enough of a threat here, and the magnitude of that threat is big enough, that we should at least be prepared,” he told attendees.
What can radiologists do?
In order to mitigate potential risks related gadolinium deposition disease, Harvey recommends using gadoteridol (Prohance) unless there are clinically clear reasons to choose an alternative. Gadoteridol is associated with the least gadolinium retention, notably in the week following gadolinium-based contrast agent administration.
Argy offered the same recommendation, noting that gadoteridol has been shown to deposit less than half the gadolinium in the brain compared to other macrocyclic agents.
Harvey also called on radiologists to become more active in the decision-making process, instead of the pharmacists or technologists who often choose which GBCA to use. It would also help if industry groups took a stronger lead on discussing the topic, he said.
“This is a nice time for radiologists to become more active in the decision-making about how these (agents) are chosen,” he said. “My opinion is at this point, there’s too much industry thought; there’s too much marketing influence and there’s too many side deals that might be leading to one being chosen over another, not a data-driven approach.”