Imaging Pharmacovigilance Needs Overhaul

A more widespread and deeper understanding of pharmacovigilance is necessary to ensure the effective development and safe use of imaging agents, according to a leading global researcher in the field.

Chicago is the venue each year for the Radiological Society of North America meeting, which attracts around 60,000 delegates from across the globe each November.

"We need to rapidly increase awareness of the science and methodology of pharmacovigilance and make the ongoing monitoring of adverse event data of imaging agents a part of our professional safety management," Professor Micheal Knopp, MD, PhD, Vice Chair of Research in the department of radiology at Ohio State University Medical Center, told delegates at the Radiological Society of North America (RSNA) meeting, held in Chicago in late November.

"Our field (radiology) needs to understand and be trained in the underlying science, actively participate in the reporting, and learn how to draw the appropriate conclusions from the observations," noted Knopp, who is also Novartis Chair of Imaging Research at Ohio State UMC.

He said he felt reassured that for agents such as contrast media used in magnetic resonance imaging (MRI), pharmacovigilance is already well established in clinical trials, and during the preclinical development phase, safety and toxicology aspects are rigorously evaluated. But there is no room for complacency, as shown in recent years by reports of nephrogenic systemic fibrosis (NSF) associated with the use of Gadolinium-based contrast agents, and not even the most extensive clinical development program can assess all different potential clinical scenarios.

The medical imaging community is often aware of the safety profile of agents published during their development and summarized in specific package insert/prescribing information, but there is only limited awareness of observed patterns of adverse events in broader clinical practice, Knopp pointed out. Comprehensive, post-market introduction pharmacovigilance data have only been published for three contrast agents: gadopentetate dimeglumine (Magnevist, Bayer Healthcare), gadobenate dimeglumine (MultiHance, Bracco), and gadobutrol (Gadavist, Bayer).

To improve the situation, he urged healthcare professionals to regularly consult the imaging agent's specific package insert and be aware of its content and prescribing information. Also, they should be fully aware of the relative occurrences of adverse events, as well as the likelihood that such events can and do occur. He emphasized that reporting rates and observations can change over time and updated information should be consulted in regular intervals because practice patterns, comorbidities, and technological capabilities can and do change.

"With better understanding of adverse events, more appropriate and tailored indications can be developed to help patients with specific needs and risks to be most appropriately managed," stated Knopp. "Understanding relative risks between imaging agents and imaging methodologies is essential to continue to perform highly effective and safe diagnostic procedures as imaging continues to be used as a critical medical care decision even in severely ill patients."

The NSF reports shattered the perception that MRI contrast agents were totally safe, but the adverse events were remarkably well managed, and this was a success story for the regulatory and imaging communities because they reacted quickly and decisively to eradicate these issues, he stated. These cases also highlight the importance of, and need for, appropriate monitoring, awareness, and reporting to prevent similar incidents.

Overall, it should become part of radiological training for everybody to be fully aware of the imaging agent specific label and characteristics, as well as the appropriate processes to detect and report an imaging-related adverse event. While these processes were primarily developed for pharmaceuticals, they can also be used for any other imaging-related adverse event, such as a mechanical injury or burn.

Two employees of Bayer Healthcare, Petra Palkowitsch, MD, and Susan Dohanish, were listed as Knopp's co-authors for the RSNA 2011 presentation. The other co-authors were Hendrik von Tengg-Kobligk, MD, from the University of Heidelberg in Germany, and Michelle Knopp from Washington University in St. Louis. —Philip Ward