Development of a Clinically Integrated Return of Results Protocol for Genetics Research in Autism

Background: The rapid advancement of genomic research in autism is due to the growing participation of children with autism and their families, and to the implementation of increasingly powerful genomic tests. Some tests, namely microarrays, are now a standard part of the clinical assessment of children with autism. Results of these tests may have significant value for families, as they can impact diagnosis, prognosis, health surveillance and reproductive decisions. Within large-scale genetic research studies, disclosure of incidental findings is a standard ethical conduct.  However, the increasing complexity of individual child and family results, coupled with their variable clinical significance, present a challenge for how and when to communicate genetic findings (Knoppers et al. 2010). Despite several theoretical discussions, there is very limited empirical research tracking impact of genetic findings on clinical care (Fernandez et al. 2013, Johnson et al. 2012).

Objectives: Consistent with recent recommendations for large scale research studies to declare a specific process for Return of Results (RoR) (Knoppers et al. 2010, Wolf et al. 2012), our goal was to develop a contextually-sensitive protocol, that considers local health systems characteristics and constraints. 

Methods: We convened a work group to develop a RoR protocol for a data collection site that participated in two large-scale genetics studies. Over 400 families have been enrolled in studies where advanced sequencing methods are increasingly revealing complex individual child and family results. 

Results: The work group considered that general ethical standards, such as confidentiality and protection of minors, were insufficient to fully inform RoR. They identified and formulated more specific directives to guide the RoR protocol: (1) families must have consented to receiving individual findings, (2) findings must be clinically actionable, (3) care pathways potentially resulting from RoR must be clear and accessible to families, (4) likelihood of family confusion and stress resulting from the findings or due to delays in access of subsequent care must be monitored and minimized, and (4) potential impact on health systems resources must be monitored.  

Conclusions: Our resulting RoR protocol is contextually sensitive and integrates RoR from research with healthcare capacity and constraints. Current empirical application of this protocol provides guidance for the integration of next-generation sequencing methods into clinical care.