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Broad Population Genetic Screening Still Faces Implementation Challenges

Silas Inman
Broad population-based genomic screening has the potential to improve patient care by detecting genetic causes of disease before they occur; however, the economics behind this approach have not fully been validated, according to a session on the clinical and economic utility of whole-genome sequencing at the AMCP Nexus 2019 meeting.
Broad population-based genomic screening has the potential to improve patient care by detecting genetic causes of disease before they occur; however, the economics behind this approach have not fully been validated, according to a session on the clinical and economic utility of whole-genome sequencing (WGS) at the AMCP Nexus 2019 meeting.

"We don't really have very many good models out there now that are looking at the cost effectiveness. We do need to quantify the costs but doing so is complicated," said Laney Jones, PharmD, MPH, assistant professor, Geisinger, during the presentation. "The personal utility of genomic knowledge is often missing from these current models."

The current methods for genetic testing include chromosomal microarray (CMA), which is designed to detect copy number variations and gene duplications and deletions. Broader testing techniques include whole-exome sequencing (WES) and WGS. In addition to deletions and insertions, WES, which focuses on 1% to 2% of the entire genome that contain 85% of the genes related to hereditary diseases, can also identify missense, nonsense, and splice site mutations. The broadest approach, WGS, covers DNA variations that can affect gene activity.

"There are 5200 genetic disorders for which the molecular basis is known," said Lon Castle, MD, chief of Lab and Specialty Drug Services, eviCore healthcare. "With WGS, you get the full genome. Just imagine the amount of genetic information you're getting there and how long it takes to sift through it and how long it takes to get it right. There's a lot of curation that has to go into those results. There's a lot of bioinformatics that goes into WGS and WES."

Geisinger Experience With Population Screening
The Geisinger hospital network launched a broad population level genetic screening program labeled MyCode in 2007. The hospital system, which is located in central Pennsylvania, has 2800 providers and 1.5 million active patients across 13 campuses. Tied to this, from a payment perspective, the Geisinger health plan has over 580,000 members and covered approximately 40% of those in the MyCode project.

Overall, 253,108 patients participated in the MyCode project, with samples provided for 172,819. Of these, 64,309 were analyzed with clinical results reported for 1068. The majority of these patients were of European ancestry (97%) with a median age of 59.21 years. The project looked specifically at the diseases indicated as tier 1 for genomic application by the CDC: hereditary breast and ovarian cancer (HBOC) syndrome, Lynch syndrome, and familial hypercholesterolemia. These conditions are expected in 1 in 400, 1 in 440, and 1 in 250 individuals, respectively.

Overall, BRCA1/2 mutations were found in 290 of these participants (27%), indicating HBOC. One hundred twenty-five (12%) had APOB or LDLR gene alterations, indicating familial hypercholesterolemia, leading to early onset coronary artery disease and stroke. There were an additional 101 patients (9%) who tested positive for Lynch syndrome, indicating the potential for early colon, uterine, and other cancers.

Of those detected, 42% did not have any evidence of a personal history of cancer and 50% did not have any evidence of a family history of cancer, suggesting that current screening methods would have missed these patients. Two-thirds of the detected individuals (68%) were eligible for risk management.

Not only did the detection of hereditary risk impact the individual who was tested but it also had implications for the rest of the family members who did not previously have a known family history of cancer. Findings from the Geisinger project aligned closely with previously reported results from JAMA, which showed that 55% of those detected by population screening did not meet the criteria for indication-based testing, according to National Comprehensive Cancer Network (NCCN) guidelines.1
 
"From this initial report and through our primary care docs and other providers in our system learning more about the MyCode project and its implications to clinical care, they've really pushed for the translation of this research project to be transitioned to clinical care," said Jones.

Following this push, population-based genomic screening was incorporated into 2 Geisinger clinics. There have been 679 patients as of August 2019 that had consented to the testing, with results received for 527. Of those tested, 527 were negative and 14 tested positive (2.6% yield).

"We're looking to anticipate care for disease prevention instead of reacting once someone has a disease," said Jones. "This strategy allows us to do earlier detection of disease and enables better management and improved outcomes. This provides more reliable identification of the risk of disease for patients and their facilities."



 
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