Utilization of a telehealth platform

Between 2016 and 2018, a HIPAA-compliant EHR-agnostic genetics tele-engagement platform called Consultagene was developed at BCM to improve access to genomic care and education for individuals with limited access to a genetics specialist [14]. This virtual platform offers comprehensive services, including patient scheduling, medical document sharing, interpretation of genetic test results, tele-genetic counseling, and educational videos for patients and healthcare providers, which are available in multiple languages including Spanish. The platform’s features are modular, which allows it to adapt to the unique needs of both clinical and research settings. Healthcare providers and patients themselves can submit a referral request through Consultagene for a patient to be scheduled and seen by one of BCM’s clinical genetic counselors via video conference. Referrers are also able to submit a request for a “peer-to-peer” consultation, whereby they can consult with a BCM provider through the platform and obtain genetics advice on any given case. Since 2019, Consultagene has clinically engaged patients requiring counseling for prenatal testing, preconception, and in vitro fertilization considerations, as well as specialized consultations related to cancer genetics and neurodegenerative diseases such as Huntington’s disease and Alzheimer’s disease. Project GIVE presents a novel use of this technology in a research setting that caters to the pediatric rare disease population coupled with the delivery of GS.

Inclusion and exclusion criteria

Children who are 0–18 years of age are eligible to participate in Project GIVE if they reside in the RGV and have a suspected underlying genetic etiology for their medical presentation. Families must primarily speak English or Spanish to participate. Participants are not eligible if they already have a genetic diagnosis that explains their symptoms. In this phase of the study, Project GIVE assesses children within an outpatient setting. Neonates with suspected genetic disorders are directed to Consultagene for evaluation following their discharge from the hospital.

Selection of study site, participant recruitment, and application review

In collaboration with UTRGV, the UT Health RGV Pediatric Specialty Clinic in Edinburg, Texas was strategically selected as the primary study site because of its ease of access for families. Additionally, there is a diverse range of pediatric subspecialists in this single facility, including a neurologist, a developmental pediatrician, and a pulmonologist, which presented adequate opportunities for patient referrals. The Consultagene kiosk was set up in this clinic for families to engage with the Project GIVE genetics team located in Houston.

Project GIVE has been designed to recruit approximately 100 pediatric participants from the RGV between February 2022-January 2024 (Fig. 1) for genetic evaluation and GS. Prioritizing inclusion and access to care, the referrer base for this study has been extended to a wider network of healthcare professionals in this region, including physicians, nurses, nurse practitioners, medical assistants, early childhood intervention (ECI) specialists, as well as physical, occupational, and speech therapists taking care of children with complex medical needs in rehabilitation centers. The UTRGV pediatricians, along with the project’s local research coordinator (R.S.), who has a background in social work and prior experience at a local geneticist’s office, work together to identify community healthcare professionals who could potentially refer study participants. The bilingual research coordinator regularly visits clinics to proactively distribute study flyers and discuss the benefits of the study for children with complex medical conditions. Additionally, the team of clinical geneticists and the genetic counselor based in Houston conduct multiple visits to this region to engage in face-to-face meetings with local clinicians.

Fig. 1

Study timeline. a Pre-enrollment preparation included development of the IRB protocol, identification of study site at the UTRGV pediatric multi-specialty clinic in Edinburg, TX and installation of the Consultagene kiosk. b Personnel includes research coordinator and UTRGV pediatricians who participate in Project GIVE clinical meetings. We began enrolling patients shortly after receiving our first referrals. Return of genomic results appointments were scheduled once results were returned from the lab. Outreach to community providers (including genetics providers visits to the RGV and visits to clinics by our research coordinator) has been ongoing throughout the study period

The healthcare providers send in a referral through Consultagene requesting “Peer-to-Peer consultation”. After accessing the portal, the referrers are prompted to upload pertinent clinical information including available electronic health records for their patients. The Project GIVE clinical team, consisting of geneticists and a genetic counselor at BCM, the research coordinator, and the UTRGV pediatricians, convenes remotely on a weekly basis to review the referrals and ascertain those most likely to benefit from genetic evaluation.

Additionally, the study team has established a collaborative partnership with the Texas Department of State Health Services’ Texas Birth Defects Registry (TBDR), which plays a pivotal role in identifying pregnancies and infants with birth defects in Texas [15]. The registry team conducts routine visits to pediatric hospitals, birthing centers, and midwife facilities throughout Texas to identify affected individuals. The TBDR team conducts systematic reviews of medical records, and both the International Classification of Diseases (ICD) codes for birth defects and text descriptions are detailed for each patient. Information for patients diagnosed with birth defects between 2015 and 2020 in the RGV is accessible to the Project GIVE study team as approved by the Institutional Review Board of the Texas Department of State Health Services. Utilizing our established provider engagement process, our team facilitates a Consultagene referral for the patient through the patient’s pediatrician.

Delivering virtual genetic evaluation with GS and longitudinal follow-up via Consultagene

Figure 2 illustrates a participant’s journey from referral to the final study visit. Upon acceptance into the study, participating families undergo a structured three-visit protocol over one year. At the initial encounter, “Visit 1”, the research coordinator meets with the pediatric participant and their family at the study site for the informed consent process. After being consented into the study, families then access two educational videos in their preferred language that are integrated in the Consultagene platform: (1) Basics of Genetics, and (2) What to Expect at a Genetics Clinic Visit. Due to the lower genetic health literacy levels of many of the study participants and their limited exposure to genetics, these videos provide relevant context to the patients regarding the research study. Families complete a five-question survey, including three 5-point Likert scale questions about their perspectives on the eduational videos and two knowledge questions related to the content covered in the videos. Following this, the clinical geneticists and genetic counselor, located in Houston, conduct an in-depth remote evaluation and physical exam of the pediatric participant through Consultagene’s videoconferencing platform. The virtual assessment is facilitated by the research coordinator present at the study site. Anthropometric measurements, including weight, height, and head circumference, are gathered for all participants by a medical assistant at the study site.

Fig. 2

Project GIVE evaluation process. Participants participate in 3 study visits over one year. KFM = known familial mutation. * indicates timepoints in which survey data is collected from families (including demographic information, perceptions of genetics, and experiences receiving genetic test results). a KFM of affected/unaffected siblings or family members or other genetic testing (ex. RNA sequencing) may be recommended by the study team to help resolve a VUS

The research coordinator is also responsible for collection of buccal samples for proband, duo, or trio GS and coordinating transfer to Baylor Genetics, a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory in Houston, TX, where a clinical GS report is generated. Families can opt-in to receiving the ACMG medically actionable secondary findings during the consenting process [16]. The genetics evaluation and GS studies are both carried out as part of the research study and are not billed through families’ insurance.

When the clinical team receives the GS results in ∼ 4–8 weeks, a videoconference return of results (ROR) call is scheduled with the families for “Visit 2”. Positive cases undergo an in-depth review of the diagnosis and medical management, with accompanying informational letters crafted for both providers and patients, in their preferred language. The Project GIVE’s clinical team facilitates follow up appointment referrals in the RGV whenever possible. In cases where it is clinically necessary, patients are directed to specialty clinics at Texas Children’s Hospital (TCH) in Houston, which is approximately 350 miles away from the study site. When a variant of uncertain significance is ascertained, familial testing is undertaken to interpret the genomic results. In the event of a negative GS result, further exploration of any research findings detailed on the GS report takes place, including clinical labs/imaging, and/or GeneMatcher submissions. Additionally, selected patients are referred to additional research studies like the Undiagnosed Diseases Network.

“Visit 3”, occurring approximately 6 months post-disclosure, serves as a follow-up to collect additional medical information about the child and review the GS results again. A detailed summary of each visit is meticulously documented and promptly shared with the referring providers through the Consultagene portal to facilitate effective communication.

Enhancing genomic competency of healthcare professionals

A critical component of Project GIVE involves training and educating referrers to ensure expeditious patient referrals to genetic services. In 2023, we developed and delivered two Continuing Professional Education (CPE) seminars designed to cater to the unique needs of non-genetics providers in this region. The content for both events focused on the importance of genetic testing and recognition of rare diseases in pediatric patients. When designing the curriculum for these events, our goal was to help local healthcare professionals develop greater confidence in referring patients to genetics, understanding different genetic testing methodologies, and interpreting genomic results at some level to address families’ basic inquiries. Additionally, we introduced conference attendees to Face2Gene [17], a machine-assisted technology for identifying patients eligible for genetics referral. Attendees also received updates on the regional impact of Project GIVE. At the September 2023 CPE event, attendees completed a pre-CPE survey that collected provider and clinic information and asked questions about how comfortable providers were with ordering, interpreting, and explaining different genetic tests. They also completed a post-CPE survey that allowed them to answer the same questions about comfortability with genetic tests. Responses for the pre- and post-CPE surveys were linked using a study ID that was randomly assigned to the attendees. Survey data were analyzed using descriptive statistics, and responses for the comfortability questions were paired to assess whether there were changes in responses at the two time points.

Expected study outcomes

The primary outcome measure of Project GIVE is TTD of rare diseases, with the starting point designated as the date when a healthcare provider initially referred the patient to Consultagene. Patients are longitudinally followed for a duration of up to one year post-referral. Event time is computed in months as the time from referral to the date of ROR.

Additionally, we have incorporated harmonized surveys developed by the Clincial Sequencing Evidence-Generating Research (CSER) consortium that were designed to study the effectiveness of integrating genomic sequencing into the clinical care of ethnically diverse and medically underserved individuals [18,19,20,21]. These measures are suitable for participants with low literacy levels and are fully translated into the Spanish language. Survey data are collected to characterize sociodemographic variables, literacy, understanding, perceived utility of sequencing, and satisfaction with the ROR process. Surveys are administered to families at each of the three study visits. As the study design of Project GIVE is the specific emphasis of this paper, the TTD analysis and the survey data regarding participants’ experiences will be explored in a forthcoming publication.