CHICAGO – A year into the partnership between the Medical University of South Carolina (MUSC) and Helix, enrollment in the large-scale In Our DNA SC population genomics program is accelerating, though the organizers have a long way to go to achieve a primary goal of making access to precision medicine reflective of the diversity of South Carolina.
As of Friday, the program had enrolled 17,681 patients, according to Caitlin Allen, a research coordinator for In Our DNA SC. That is about 1,100 more than Allen had reported just a week and a half earlier at the American Medical Informatics Association (AMIA) annual symposium in Washington, D.C. "We're growing on a daily basis," said Allen, a social and behavioral scientist at MUSC with an interest in precision public health.
Among the first 16,000 patients enrolled, 73 percent were female and 16 percent were people of color in a state where one-third of the population is nonwhite. The median age of the enrolled cohort is 51.
About 7,000 of the 16,000 enrollees have provided samples. The split is nearly even between at-home kits or in-person collection at MUSC clinics and community events, according to Allen.
Right now, patients have to make an appointment to provide a sample at a clinic, but Allen expects that it could be expanded to walk-ins in the future. Another enhancement under consideration is expanding collection points to labs.
In Our DNA SC is only collecting saliva samples right now, but Allen said that program organizers are looking at the possibility of collecting blood as well.
Allen described In Our DNA SC as a community health research project and said that MUSC is interested in community partnerships to ensure that the program is building a cohort that more closely resembles the population of South Carolina. The university is running the program with just four research coordinators, so it is relying heavily on Helix and community partners throughout the state.
The program has expanded to 25 clinical sites from the original 10. Eight of the 10 clinics involved in a pilot phase were located in Charleston County. Participation has since expanded across the state, but Allen said that the cohort is still somewhat skewed to the Charleston area and other regions where the MUSC Health system has a significant presence.
The health system does have a group of partnerships collectively known as the MUSC Health Regional Health Network, which it is leaning on to increase the reach of In Our DNA SC.
The long-term partnership aims to enroll a total of 100,000 South Carolina residents, providing them with no-cost testing for 11 genes associated with the US Centers for Disease Control and Prevention's Tier 1 conditions, namely hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia. The goal is to improve healthcare outcomes by integrating genetic insights into both clinical care and translational research.
The program includes a registry for patients who are at elevated risk for Tier 1 conditions.
About three-quarters of those who are positive for CDC Tier 1-related variants have opted to receive genetic counseling, according to Allen. "Then they're able to be seen very quickly," she said. "That's important to us, too, to make sure that they're getting into the genetic counselors at MUSC quickly."
So far, the program has identified 48 people with Tier 1 conditions. About 75 percent of these have agreed to genetic counseling, Allen said. She added that about 90 percent of those identified as being at risk for a Tier 1 condition would have been missed using "traditional" screening methods.
In Our DNA SC marked its one-year operational anniversary on Nov. 8, the same day Allen presented data on the first 16,500 enrollees. MUSC and Helix announced their partnership in September 2021.
The program is an example of One MUSC, a strategic vision launched in the spring of 2021 to enable the healthcare organization to incorporate new research and evidence-based approaches into routine patient care with the goal of continuous quality improvement.
MUSC is using Helix's Exome+ assay that combines whole-exome sequencing, targeted panels, and microarray testing. The In Our DNA SC program also follows Helix's "sequence once, query often" model and end-to-end integration platform to enable the use of genetic insights.
At AMIA, Leslie Lenert, director of the MUSC Biomedical Informatics Center, said that In Our DNA SC is sticking with exomes for now, largely because whole genomes require so much more data storage. However, Lenert said that the program might look at whole-genome sequencing at an undetermined point in the future.
A major goal of In Our DNA SC is to "move away from the 'one-size-fits-all' approach to healthcare delivery and to instead tailor treatment and prevention strategies to people's unique characteristics, including environment, lifestyle, and biology," Allen said.
Negative test results are automatically returned to participants who opt in to receive results through the MyChart portal in MUSC's Epic Systems electronic health record and, if they choose to set up an account, through the Helix portal. Positive tests have an automatic hold for a research coordinator to contact the patient by phone and, if they don't respond to calls, by certified mail, to be connected to a genetic counselor.
The biomedical informatics team at MUSC created a SMART on FHIR app to integrate with MyChart for patient enrollment. SMART on FHIR is a framework officially called Substitutable Medical Apps, Reusable Technology (SMART) that follows the Health Level 7 International specification known as Fast Healthcare Interoperability Resources (FHIR).
Helix has built its own integration with Epic to send results as discrete, computable data directly to the EHR and the MyChart portal. Eventually, this data will help inform clinical decision support systems.
"We really want to have the data be useful from a clinical perspective and make sure that we're able to inform and have clinical decision support at the point of care," Allen said. The first use case for this is pharmacogenomics, though that application is still in the early stages.
A paper that appeared in the Journal of Personalized Medicine in July described outcomes from the pilot phase of the program, which ran from Nov. 8, 2021, to March 7, 2022.
The pilot phase was meant to identify factors that influenced patient engagement and to examine strategies that can make In Our DNA SC sustainable.
The researchers invited adults a week before their appointments at MUSC-affiliated outpatient clinics by sending messages through the MyChart patient portal. Follow-up messages were sent three days before the appointment. Those choosing to participate could fill out an electronic consent form, which would trigger a standing order for a clinician to collect a sample during the appointment.
For the pilot, MUSC contacted 18,887 patients about In Our DNA SC program. Some 5.4 percent, or 1,027 people, got to the consent phase.
The researchers collected quantitative data about training materials and patient and clinician perceptions of In Our DNA SC at the 10 pilot sites.
The Journal of Personalized Medicine article said that Black invitees were least likely to see the invitation sent through MyChart. "Common concerns limiting reach and participation included privacy and security of results and the impact participation would have on health or life insurance," the team led by Allen wrote.
Other respondents raised concerns about the security of genetic information and the design and content of the consent form, according to an abstract presented at AMIA.
The consent form was initially a 20-page PDF document. Within a few months, the program coordinators had added pictographs to make the form simpler to understand and had developed five comprehension questions. During the pilot, there was no significant difference in decision-making scores between the two forms or in perception of the program, according to Allen.
Further enhancements will include embedded videos, Allen said. The MUSC Biomedical Informatics Center is supporting the program by developing applications to promote patient recruitment, enrollment, and participation.
Within MyChart, the investigators initially found that people were clicking a button to show interest but erroneously thought they were consenting to the study. MyChart did not actually support one-click consent at the time, according to Allen.
The program thus developed a text message that is triggered when someone clicks in MyChart to express interest in the study. The message includes a link for users to fill out the consent form on their smartphones. Manual outreach by phone from research coordinators is available for those who need it.
MUSC has recently begun to send tailored messages from "provider champions" through the portal and by text to improve engagement, according to Allen.
Sample kits are sent to Helix for testing. Helix promised to return the results in about eight to 12 weeks. Allen said that since collection started a year ago, average turnaround has been 33 days, and 95 percent of results have been returned within eight weeks.