Researchers Differ on How to Manage Incidental Findings

Disparate views on managing incidental imaging findings made during clinical research — particularly for unclear results — signal a need for standardized guidance, according to recent survey results.

Respondents were split on whether it was the site primary investigator’s responsibility to decide which incidental findings should be reported back to the patient, and the most commonly cited challenges included adequately explaining these findings and the follow-up required. These issues were most present when dealing with nonspecific incidental findings or findings of unclear importance, said lead author Jane S. Kang, MD, a bioethicist and associate professor of medicine in the Division of Rheumatology at Columbia University Irving Medical Center, New York City.

“It can be difficult to have a clear approach” when it comes to these situations that are not black and white, and it is hard to get a clear answer, she told Medscape Medical News.

The survey included responses from investigators from the Treatments Against Rheumatoid Arthritis and Effect on 18F-fluorodeoxyglucose (FDG) PET/CT (TARGET) trial, conducted between 2015 and 2021. The 24-week trial included patients from 28 centers in the United States to investigate how different disease-modifying antirheumatic drugs can reduce cardiovascular and joint inflammation, assessed via whole body FDG PET/CT. The survey was a planned substudy of the TARGET trial and is “the first study that examines researchers’ attitudes and beliefs regarding incidental research findings from whole body FDG PET/CT,” Kang and her coauthors wrote.

Medscape Medical News reported the main results of the TARGET trial in 2022.

Eighteen of the 28 site primary investigators (PIs) of the TARGET trial participated in the survey, which was published in Arthritis Care & Research in September 2024.

TARGET Trial Incidental Findings

The TARGET trial enrolled 159 patients, of whom 82% had at least one incidental finding and 62% had one or more FDG-avid incidental findings. There were 46 “clinically actionable findings” for 40 participants overall; the reading radiologists recommended additional imaging for 28 findings and specialist consultation or procedural evaluation for 15 findings.

Details on these incidental findings were presented in a poster at the American College of Rheumatology (ACR) 2024 Annual Meeting, held in Washington, DC.

The most common non-FDG–avid findings were pulmonary nodules, diverticulosis, cholelithiasis, sinus disease, and vascular calcifications. The most common FDG-avid findings were hypermetabolic lymphadenopathy, increased gastric/esophageal uptake, increased bowel uptake, and increased pharyngeal uptake.

In the related survey, 11 respondents (61%) said they returned any incidental findings to participants and five (28%) did not; the remaining two respondents did not know.

Across all study PIs, 22% felt that incidental findings were beneficial, 39% said they were potentially beneficial, and 11% said they were potentially detrimental. PIs that ranked incidental findings as potentially detrimental pointed to how these findings led to invasive additional testing.

“One of my subjects was found to have diverticulosis, which needed an invasive procedure to rule out malignancy,” one respondent wrote. “However, the subject had already had a colonoscopy months prior to the PET findings, which was still not deemed sufficient by the nuclear radiologist and GI consultant, so he had to have another colonoscopy, which was benign, but uncomfortable.” 

Obligation to Return Findings

All investigators agreed that incidental findings should be shared with patients if they revealed a high-risk medical condition that can be treated; had important health implications such as premature death or substantial morbidity; and their health could be improved with proven preventive or therapeutic interventions.

There was more disagreement on whether to share that the FDG PET/CT revealed no findings or if the test revealed a finding without clear medical importance of which the research participant may not be aware.

An example of a less-specific finding could be something like increased FDG uptake in a particular area, like the bowel, Kang explained.

“The question is: What does that mean?” she said. “How do you interpret that?”

While some PIs might feel obligated to share all results with patients, sharing ambiguous incidental findings will likely not be helpful to the patient, said Arthur Caplan, PhD, of the Division of Medical Ethics at the NYU Grossman School of Medicine in New York City.

“Dealing in unknowns and uncertainties when you’re diagnosing doesn’t really do people very much good,” he told Medscape Medical News.

While most survey respondents said they were at least moderately obligated to disclose incidental research findings if a patient requests them, Caplan noted that it was ultimately the researchers’ decision.

“Patient preferences are something to take into account, but they’re not final. If the research team says, ‘we don’t know, it’s too uncertain, it’s too new,’ then I don’t think they have any obligation to return that [information],” he said. “You can’t tell somebody what you don’t understand.”

Conversely, the clearer the incidental finding, the stronger the obligation to share that information with research participants, he continued.

Need for a Standardized Approach 

The TARGET study, like many research studies, left the management of incidental imaging findings to individual research sites and investigators.

It’s possible that different sites responded to these ambiguous clinical findings in different ways, Kang noted.

“If there’s a situation that’s difficult to interpret as it is, you can imagine that the resulting actions that may result from that can vary, too,” she said, which highlights the need for more specific and standardized guidance.

One way to approach this, Caplan noted, is establishing an agreed-upon approach for dealing with any incidental findings across all research sites before a study begins.

“If there is going to be a common study at many sites, then they should have a common response on what they are going to do,” he noted, and how they will share that information effectively with the research participants to ensure it’s understandable. However, in a lot of research studies, each site has its own approach.

“Right now, it’s all over the place and that shouldn’t be,” he said.

Institutional review boards (IRBs) could be one resource to help build detailed guidance on managing unclear incidental findings in future research, wrote Kang and her coauthors.

“For incidental findings from whole body FDG PET/CT that are not clearly actionable or less straightforward, IRBs may consider requiring a certain level of follow-up for different categories or types of incidental findings or require that all incidental findings are reviewed by an independent group that would provide timely recommendations on the most appropriate return and management of those findings,” Kang and colleagues wrote. “With IRB guidance, very specific and detailed policies and procedures for returning and managing incidental findings should be established for every study, with consistency among the research sites of multicenter trials.”

The TARGET trial and survey were funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Kang reported receiving research funding from the National Institutes of Health and the Rheumatology Research Foundation. Caplan serves as a contributing author for Medscape Medical News and served on an independent bioethics panel for compassionate drug use that was funded by Johnson & Johnson through the NYU Grossman School of Medicine.