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Non-Genetics Healthcare Providers Can Effectively Return Sequencing Results, NSGC Study Finds

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NEW YORK — Healthcare providers in the neonatal intensive care unit given some genetics training can effectively return sequencing results to families, according to a study presented at the virtual annual meeting of the National Society of Genetic Counselors last week.

As part of its SouthSeq program to use whole-genome sequencing to diagnose infants in the NICU across the southern US, HudsonAlpha Institute for Biotechnology researchers also trained providers to return those sequencing results.

Based on the return of 330 results, Meagan Cochran, a genetic counselor at HudsonAlpha, found that non-genetics NICU providers with some training returned results effectively more than 90 percent of the time. Although some errors were made in the return of a portion of results, most were minor, she noted. 

In her talk, Cochran called the results "very encouraging."

For SouthSeq, which has $10 million in US National Institutes of Health funding, HudsonAlpha has partnered with hospitals in Mississippi, Alabama, Kentucky, and Louisiana. It aims to enroll 1,500 newborns suspected of having a genetic disorder or other birth defect, and is focusing on newborns from underserved populations in the South, including from African-American families and rural populations — groups that have typically not had access to whole-genome sequencing as a first-tier diagnostic test, Cochran noted.

So far, 407 probands have been enrolled in the study and 90 percent undergone full analysis. In addition, 29 percent received a primary diagnosis with an either pathogenic or likely pathogenic finding. Seven probands underwent rapid whole-genome sequencing and 57 percent received a diagnosis. Cochran noted that the higher diagnostic rate was likely due to increased selection for suspicion of a single-gene disorder.

As part of the study, genetic counselors from HudsonAlpha provided training to NICU healthcare providers on returning sequencing results. Training followed a half-day protocol and involved in-person didactic teaching, small group discussions, hands-on activities, and simulations. As some providers joined later in the study and due to COVID-19 pandemic restrictions, training was also offered virtually. Thirty-two NICU providers have undergone training and, following training, said they felt more comfortable both interpreting whole-genome sequencing results as well as managing patient care based on sequencing results.

As part of the study, 330 results were returned to patients' families and were randomized both by site and result type to either be returned by genetic counselors or the trained NICU providers. The results were returned in person, by phone, or by certified letter, with more returned by phone during the COVID-19 pandemic. The return of results sessions conducted by both arms of the study were recorded.

Genetic counselors then analyzed sessions conducted in the experimental arm to gauge whether the NICU providers made any minor, major, or high-risk errors. Minor errors included those that would not affect patient understanding or decision making, while major errors affected critical details and could influence patient understanding or decision-making. High-risk safety errors, meanwhile, were likely to have an immediate detrimental effect on patients. Both major and high-risk errors led to immediate feedback and, in the case of high-risk safety errors, reporting to the study's safety board.

So far, 98 return-of-results sessions have been reviewed, Cochran reported. For 58 percent of the cases, the providers made no errors and in a further 33 percent, made minor errors. Major or high-risk errors occurred in 9 percent of cases.

The most common major error they observed was the overinterpretation of negative results, such as implying that as the result is negative, the child's condition is not genetic, she said. Another common major error was misstating family members' recurrence risk. Minor errors, meanwhile, included forgetting to discuss negative secondary results.

The errors, Cochran noted, were generally spread evenly among the type of results being returned — negative, uncertain, or positive results — with a slight bump by proportion among uncertain results for major errors.

"That's to be expected, given the complex nature of these uncertain results and the nuance that can go along with them," Cochran said.

She added that she and her colleagues plan to next analyze the return of results given by genetic counselors to establish a baseline error rate. They have already noted that genetic counselors tend to spend more time returning results than the other providers.