The AutGO Initiative: A Conceptual Framework for Developing Genetics-Outcomes Research Hypotheses

Abstract

The increasing emphasis on translational approaches to complex neuropsychiatric and neurodevelopmental conditions research requires scientists from a broad range of disciplines to build dynamic collaborations when formulating hypotheses and framing study designs. The need to integrate the knowledge and perspectives not only from multiple scientific silos but also from the populations impacted by these conditions presents a significant challenge to researchers, particularly for a heterogeneous condition like autism. As one path toward addressing these challenges, we have previously introduced Autism Genetics Outcomes (AutGO), an initiative to support broad stakeholder partnerships and promote a new integrated concept called GO (i.e., research approaches that draw on both genetics and clinical outcomes perspectives). Herein, we developed a workflow for collecting stakeholders' feedback toward the development of a GO hypothesis. AutGO is an evolving initiative, and here we describe how its three essential components (conceptual framework, applicability, and implementation) have been developed. As a proof-of-concept, the AutGO team sought to demonstrate how a GO hypothesis could be developed using a semi-structured literature review workflow. We also developed a prototype from published reports and formulated a GO hypothesis for autism. Rather than seeking community stakeholder input after a research project is conceptualized and designed, the developed conceptual framework demonstrates the feasibility of formulating scientific hypotheses by engaging stakeholders in retrospective semi-structured literature reviews. The presented workflow, prototype, and discussed recommendations will bring awareness in the autism research community about the benefits of applying the GO approach in order to promote translational aspects in genetics research. LAY SUMMARY: We used a community-based engagement approach to develop AutGO (Autism Genetics Outcomes), an initiative to establish stakeholder partnerships and to promote research approaches (we refer to as GO) that draw on both genetics and clinical outcomes perspectives. Specifically, we developed a conceptual framework that includes a literature review process for developing GO hypotheses and stakeholder feedback collection protocol. Our work will bring awareness in the autism research community about the benefits of integrating patient perspectives in genetics research. Autism Res 2020, 13: 1286-1299. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

Keywords: autism; conceptual framework; genetics; engagement; outcomes; stakeholders; translational research.

Figure 1

Semi‐structured literature review workflow. AB: advisory board; EP: Expert panel. The workflow was developed by incorporating participants' feedback obtained through other project activities: the AutGO workshop, in‐person meetings, and the educational webinar.

Figure 2

Graphs A and B show the scores given by each stakeholder group in Tier‐I and II assessments, for the topics of “depression in autism” and “probiotics in autism,” respectively. In both Tier assessments, team members were answering the same question: “Please indicate to what extent you would recommend each topic with “0” indicating “Would not recommend” and “10” indicating “Would highly recommend.” Uniform trends are seen when comparing the scores, even though, the two assessments were done independently by each participant. Of note, some members belonged to more than one stakeholder group and, in calculating averages, their scores were counted in all the groups that they have represented. Identifying why given topics may be perceived differently among stakeholder groups was beyond the scope of this study. Assessing such topics would require a larger sample size and different study designs. Stakeholder groups include Researchers (R) [R. Autism, R. Outcomes, and R. Genetics], Clinicians, Parents, and Others.

Figure 3

Prototype: A research finding exemplifying the GO concept. One example of a potential GO project is the successful story of the reported relationship between a variant in a gene called MET and GI issues in autism. Even though several factors in this model still remain unknown, taken together they led to a meaningful hypothesis and further highlighted the connection between gut and brain function [Campbell et al., 2009]. Connecting parent reports with genetic information contributed to this scientific discovery, positive outcomes of which have been reflected in some case reports.

Figure 4

Schematic illustrating the potential value of incorporating anecdotal evidence in research. (A) One way to do so is to form multidisciplinary teams, such as AutGO, and incorporate stakeholders' perspectives in the research development process. (B) Phenotypic data representing patient profile may come from three different sources: research level, electronic health record, and self‐reported data, and be categorized as structured, semi‐structured, and nonstructured, respectively. The AutGO initiative provides a platform for the concept development and potential future directions.