Returning Clinical Genetic Results on a Large Scale to Research Participants in SPARK

Background: A common issue in genomic research is whether investigators have a responsibility to return individual genetic research results to research participants. The National Academy of Medicine Report on Returning Individual Research Results to Participants recommends returning such information when feasible. Returning individual research results builds partnerships with participants, provide them with valuable information, and connects them to communities of individuals with similar characteristics. However, returning results requires additional resources from sponsors and researchers and is particularly challenging for large studies. Understanding the benefits and challenges of these processes is important as the number and size of genomic research studies increase.

Objectives: We sought to build a scalable process for returning genetic results related to the participants’ autism spectrum disorder (ASD) diagnosis in participants in SPARK, a large recontactable research cohort of tens of thousands of individuals with ASD and their first-degree family members. Using an online platform and a telehealth genetic counseling service, we have returned individual genetic findings to 21 participants and plan to return approximately 200 results by May 2019.

Methods: 457 families were recruited to SPARK online (https://sparkforautism.org) and provided consent to receive genetic results. Individual genetic results related to autism that met ACMG pathogenic or likely pathogenic criteria were identified in 10.8% of families. A committee of medical geneticists reviewed variant and phenotypic information for all families, and results were confirmed in a CLIA (Clinical Laboratory Improvement Amendments) certified laboratory. Participants were notified that they had a genetic result by email and were given the option of receiving their results through their own medical provider or a study-provided geneticist/genetic counseling service by telephone. Educational materials about receiving a genetic diagnosis and their specific genetic condition were provided with a copy of the clinical genetic report prior to the result disclosure appointment. Participants provided feedback to the study team about the importance of receiving their results and satisfaction with the process.

Results: As of November 2018, we returned genetic results to 21 participants, including 20 parents with dependent children and 1 independent adult. Nineteen of the results were de novo and 2 were inherited from unaffected mothers. Six of the participants chose to receive the result through their own medical provider and 15 used the SPARK-provided geneticist or genetic counselor. On average, participants completed authorizations to receive results 8 days (SD= 16.0) after notification, and the 15 who received results through SPARK had appointments with the geneticist/genetic counselor 13 days (SD= 10.5) after completing their authorization. Participants indicated that they understood the next steps to take with their results and that they felt positively about having received a genetic cause for their child’s autism and participating in SPARK.

Conclusions: We are able to return clinical genetic results using efficient, scalable processes. This is an effective way to engage participants and increase satisfaction with SPARK research participation. There are challenges to returning individual genetic results at scale, including but not limited to communication of inherited findings and ensuring that participants understand with the implications of the results.