NEW YORK — Before samples are even collected, pediatric patients can face a variety of barriers to receiving exome sequencing and other genetic tests, such as insurance authorization and delays in scheduling appointments.
Most rare childhood diseases are thought to be genetic, and the use of DNA sequencing to diagnose childhood conditions has been on the rise. Recent guidelines, for instance, have called for exome or genome sequencing to be implemented as a first- or second-tier test for children with intellectual disability, developmental delay, or multiple congenital anomalies.
Being able to get a molecular diagnosis quickly and early has been a key draw of sequencing tests, as they could circumvent the diagnostic odyssey many patients with rare diseases face. One research focus has been on faster and faster turnaround times for pediatric clinical exome or genome sequencing, particularly in neonatal intensive care scenarios. In 2015, for instance, researchers from Children's Mercy Hospital in Kansas City reported that they could receive provisional whole-genome sequencing results in just over a day.
But in the outpatient setting, just getting access to testing can take months. Insurance coverage, accessibility of genetics experts, and sociodemographic factors such as a family's primary language and neighborhood resources, many of which may be intertwined, can all affect testing access.
"I don't think that people always realize what it takes to get that sample to the lab. There's a lot of hype about diagnostic yield of exome sequencing but just thinking about how we're ensuring that access is equitable, and making sure that we have a deliverable process, is not always emphasized," said Monica Wojcik, an attending physician in the divisions of newborn medicine and genetics and genomics at Boston Children's Hospital.
A recent study from Stanford Medicine researchers appearing in Genetics in Medicine found that pediatric outpatients in their analysis waited, on average, slightly more than 104 days to undergo exome sequencing, though that time frame varied widely from five days to more than a year.
The study focused on patients who eventually underwent exome sequencing, rather than all patients who might have sought and been denied testing. "We really wanted to focus in on: 'Of those who get an exome in a best-case scenario, how long is it taking them? How different is that in a cohort?,'" said senior author Lindsay Killer, a genetic counselor at Guardant Health who was with Stanford Medicine at the time of the study.
When they broke the timeline down, she and her colleagues found that patients waited an average 34.4 days for prior authorization from their health insurer and an even longer period, an average 48 days, after that decision to return for an appointment to undergo informed consent and submit a sample for exome sequencing.
Socioeconomic factors, they found, influence how long the interval between requesting prior authorization from insurance and sample testing is. Higher household income, as gauged by neighborhood postal codes, led to shorter insurance decision times, for instance. For every $1,000 increase in median household income, they calculated a 0.4-day shorter time to insurance decision, indicating that lower household income is associated with delays in care.
In addition, patients with private insurance had slightly shorter wait times for an insurance decision than those with public insurance, about 100 days compared to 116 days. Most patients in the study had private insurance.
Prior authorization requests are sought for genetic testing more broadly, not just exome sequencing, even though many tests may ultimately be approved. For example, nearly 80 percent of prior authorization requests for genetic tests at two children's hospitals in Texas were approved, according to a 2021 study in Genetics in Medicine from researchers led by Baylor College of Medicine's Haley Streff. Public payors, they found, were slightly more likely to approve a request — 86 percent of the time — than a private payor, which approved it 70 percent of the time. Of those cases for which testing was approved, more than 19 percent led to a diagnosis.
The wait for prior authorization is only part of the delay. The Stanford Medicine team found in its study that the wait to schedule and undergo consent for testing and sample collection was even longer than for insurance authorization. This, they noted, could be influenced by a range of factors, such as a family's resources or accessibility and availability of medical geneticists and genetic counselors.
"I think in general that things like transportation and finances are big [factors]," Baylor's Streff noted. "For some people, having to take off another day of work, figuring out public transportation, finding childcare for their other children, those are huge barriers."
Processes with numerous moving parts like this always affect access to care, Boston's Wojcik said. "Whenever you have that multistep process requiring insurance authorization, potentially repeated visits … your patients could have difficulties in accessing care for many reasons, whether it is financial resources, education, racism," she added. "There's so many different reasons they could fall through the cracks."
In a recent Pediatric Research paper, she and her colleagues examined the influence of factors including insurance plan, primary language, and Childhood Opportunity Index (COI), a measure of neighborhood-level resources, on genetic clinic attendance. Patients from neighborhoods with low COI ratings were less likely to attend clinic, and patients from families with limited English proficiency had delays in care.
At the same time, there is a limited number of genetics professionals to even see those patients when they can get to the clinic. David Stevenson, a professor of clinical genetics at Stanford and coauthor of the Genetics in Medicine study, noted that there are limited in-person clinic slots, which could affect how long it takes to get consent from patients or their parents and collect samples.
"If your genetics providers are only seeing patients on certain days, and it doesn't work with your work schedule, you're looking at the next month, and it quite easily can spiral from there," Wojcik added.
Stevenson noted, though, that the analysis only reflects the 2018-to-2019 time frame and that new approaches adopted during the COVID-19 pandemic may have shortened the time to sample collection. For instance, telehealth approaches can now be used during the consent process.
Reducing the complexity and number of steps would make the testing process "easier for everyone," Streff said.
In their Pediatric Research study, Wojcik and her colleagues found, for instance, that having public insurance was associated with increased access to genetic testing. In Massachusetts, she noted, samples for testing may be collected at an initial visit because the way public insurance there is set up, prior authorization is not needed. By contrast, people with private insurance then have to wait for that authorization.
"Rather than trying to make a conclusion about insurance processes, I think it just demonstrates the power of being able to send a test from that first visit," she said.
Stevenson added that his group is part of a genetic testing optimization service that continues to follow all the exomes that come through the center to see whether prior authorization time and other factors affecting the testing timeline change.
"If we create these fantastic technologies, that's sort of half the battle," Wojcik added. "The other is really delivering it to people who need it and making sure that process is equitable."