FAQs for Providers
Specimen Collection
Samples will be collected at specific well-child visits. For the ABGS pilot, each patient will only have one sample collected. If the program becomes broadly available, we anticipate that patients will have several different screening panels timed at visits throughout childhood (example: 1 year WCC, 4 year WCC, 12 year WCC). Sample collection and storage is an ongoing topic of optimization for this project. There are pros and cons to having a single sample collected at an early time point, stored centrally and utilized for the series of screening tests throughout childhood, versus obtaining a new sample at each time point. Parent/care-giver and provider input will be critical to determining the optimal schedule and most effective approaches.
The study team is still trying to determine what will work best for ABGS, but there are essentially three options for DNA isolation. 1) venipuncture blood sample, 2) fingerstick dried blood spot collection, or 3) saliva/buccal swab. The decision about biospecimens is an ongoing topic of optimization for this project. While blood samples provide better quality DNA with higher success rates, we recognize the appeal of the less invasive nature of buccal swabs. It is possible that ABGS sampling could coincide with other blood sampling such as iron and lead level testing. As noted in question 1, obtaining a single high-quality sample that is used for subsequent screening panels is also an option that will be considered. Caregiver and provider input will be critical to determining the most effective approach.
We anticipate that samples will be collected during the WCC by clinic staff. Although the study team will have liaisons with the enrolling sites, we do not anticipate that these personnel will be able to conduct the sample collection. If a blood sample will be collected, phlebotomy will be performed per usual clinic procedures affiliated with well child visits. If we decide to use saliva/buccal swab collection, the study team will train clinic personnel in obtaining the specimens. In any of these scenarios the study team will ensure that the correct sample collection tubes and shipping instructions are provided.
DNA Testing Procedures
ABGS will build on traditional newborn screening priorities to include a small group of highly actionable genetic conditions. A committee including pediatricians, geneticists, genetic counselors and other experts are in the process of determining which diseases will be included on the panels based on stringent criteria focused on the effectiveness of surveillance and/or interventions to improve health outcomes in presymptomatic individuals. A complete list of conditions included in the screening program at each time point will be available to providers and caregivers. These are some examples of types of conditions that will be included: Marfan syndrome, Wilson disease, and Familial Adenomatous Polyposis.
The study team will develop and validate targeted sequencing procedures for the genes included in the screening program. We will prioritize approaches that only obtain results specific to the conditions included in the screening program (i.e. NOT whole genome sequencing), to avoid concerns related to incidental information that is “off target” or less actionable. That being said, there are a number of trade-offs related to cost and test performance that will need to be weighed in the study implementation. It is theoretically possible that the optimal sequencing method will eventually involve genome-scale sequencing with informatics approaches that select a “virtual” panel for analysis. However, we also see potential in very low-cost targeted sequencing methods that would avoid the possibility of generating unwanted information. Most importantly, the policies for return of results will be clearly stated in the consent for each ABGS panel.
ABGS Results and Disclosure Process
As a screening test, ABGS will provide either a “negative/normal” or “positive/abnormal” result, based on the nature of genetic variants that are found in each individual. Everyone has some number of common “benign” variants that are normal and do not cause a monogenic disease, even if they are found within a gene that is associated with a disease. These variants will NOT be disclosed on the report. In addition, some people have rare variants in these genes that cannot be confidently classified and are considered to have uncertain clinical significance. Since these variants have very low predictive value in an asymptomatic individual, these variants will also NOT be disclosed and will constitute a “negative/normal” screening result. In order to reduce the number of false positive results, only variants with a very high likelihood of pathogenicity (i.e. disease-causing) will be considered as “positive/abnormal” results.
Based on the aggregate prevalence of the conditions included in the ABGS panels, we estimate that fewer than 1 out of every 20 children will have a positive screening result.
Results will initially be returned to providers as an electronic PDF file and/or hard copy printed report (as preferred by the practice). We expect that each clinic will follow its standard procedures for disclosing test results to care-givers. Since most results will be “negative/normal” it would be reasonable for these results to be provided via telephone, secure electronic communication, or mail. In the rare case of a “positive/abnormal” result we think it would be appropriate for a clinical provider to call the care-giver to disclose the result and offer an expedited follow-up appointment for more detailed discussion about next steps. We anticipate that if ABGS becomes part of routine well-child care, results will be incorporated into EHR systems.
As part of the pilot, the ABGS research team will engage directly with clinical providers to prepare them for “positive/abnormal” result disclosure and follow-up with them to ensure that care-givers received the results. Each positive/abnormal report will be accompanied by a succinct document with information about the specific condition identified in the patient and a list of resources for more detailed information and family support networks, which can be shared with care-givers. In addition, providers will be given a checklist of clinical “next-steps” (e.g. lab tests, imaging, medications, and specialist referrals) for result confirmation and disease management.
A study genetic counselor will also be available as needed for a 30-45 minute telemedicine consultation with any study participant’s care-givers, at no cost to the participant.
ABGS Costs, Insurance Coverage, and Reimbursement
As a research study funded by the National Human Genome Research Institute, the pilot ABGS panels will be offered at no charge to patients. If the program becomes routine, we anticipate that such screening might be offered as a self-pay service, become a covered preventive medical service by private and public insurance, and/or be subsidized by health systems or state public health programs.
For any patient with a positive/abnormal result, follow-up management is expected to be part of their regular care, including clinic visits, laboratory tests, imaging, and specialist referrals. The ABGS research study does not include funding for follow-up care.
ICD-10 includes a billable code “Z13.71 – Encounter for nonprocreative screening for genetic disease carrier status” that we believe will be an appropriate way to document when an encounter has included a pre-test discussion about genomic screening, such as ABGS. Whether this code will be reimbursed by private or public insurance is not known. Since the ABGS pilot will be conducted as research, we do not yet know whether it will be allowable for participating providers to apply this code to obtain reimbursement for the additional time spent. This will need to be determined through human subject research ethics oversight by the Institutional Review Board.
For any patient with a positive/abnormal result, follow-up management is expected to be reimbursed as it would be for any patient with complex health conditions that require follow-up clinic visits, laboratory tests, imaging, and specialist referrals. The ABGS research study does not include funding for follow-up care. In this case, the appropriate disease-specific and/or procedural ICD codes would be applied.