NEW YORK (GenomeWeb) – Researchers from the University of Washington have made public for the first time a comprehensive and detailed description of their web tool for returning genome sequencing results to research participants or clinical patients, called My46.
The researchers published the outline in Genetics in Medicine last week, and intend to license the tool to other academic and nonprofit research organizations at no charge in anticipation of a shift toward the use of more direct and convenient systems for managing and returning genetic test results than traditional in-person meetings or counselling.
UW researchers developed My46 in 2010, and began studying it in the context of the return of research-based sequencing results in 2012 as one of seven National Human Genome Research Institute-funded projects aimed at creating policy guidelines on how and when to disclose secondary information to the subjects of genomic research studies.
Michael Bamshad, co-PI of that study with UW professor Holly Tabor, spoke with GenomeWeb this week about moving from that study to the present day, where the UW team is now studying how the tool could be valuable in returning not only research-based, but also clinical sequencing results, which the team highlighted in its report in Genetics in Medicine.
Data from the group's NHGRI study of My46 is now totally complete, and the results are awaiting publication, Bamshad said. In the meantime, the UW investigators and colleagues plan to study how well it works in the clinical arena, implement it to facilitate mendelian disease research, and talk to other groups that may want to put it to use.
"One reason for publishing this was that it really needed a formal description of it in its totality," Bamshad said. "People have heard a lot about My46 in presentations and such, but they hadn't seen the full picture."
"Also things have changed. In talking to researchers and clinical groups about how they might utilize My46, we recognized that we might need to do some additional development so it had flexibility to be used in a variety of ways," especially if it is implemented to return results in a clinical context, he added.
That new flexibility is reflected in the researchers' outline of the system last week, most importantly, their description of how it can be used within three distinct models or workflows for return results: My46-adjunct, My46-assisted, and My46 self-guided.
"The initial aim [in developing My46] was to facilitate the return of research results, because the challenge we were presented with was families undergoing research-based exome or genome sequencing for which we were to identify variants that might be valuable to them … but [without] a way to get that to them, at least no cost- and time-effective way," Bamshad said.
In research settings, there is no interpretation or recommendations made on findings that aren't supposed to be interpreted as part of the study itself, but patients can take an incidental or secondary finding to their care provider for interpretation.
In a clinical role, though, there have to be different models, Bamshad said, because of the important difference between returning results and interpreting them.
"This actually forced us to think a lot about the role of genetic counsellors in research versus clinical settings, and we really separated results return from interpretation in terms of [how My46 works]," Bamshad said.
Counsellors are necessary for the latter, he explained — for putting results in context for families. But the UW developers of My46 believe that the former can be facilitated either in part or in full using a web-based tool.
"We want to see tools like this used, because we think they can be a time saver for clinicians and researchers," without overwhelming risk to patients and families, Bamshad said.
While conventional models — in which a diagnostician and a genetic counselor work together to do everything from actually offering results, to educating families, to interpreting the results, to guiding medical management based on those results — are effective, they are also labor-intensive, and hard to scale up to the multiple genomic findings that will become more common as the use of whole-genomic methods grows.
While many institutions have implemented patient portals where individuals can access results online, My46 allows for significant additional education, management, and tracking compared to a simple portal.
"With a portal, you see exactly what the physician is seeing," Bamshad said, "which is not always useful and certainly can be anxiety provoking."
However, it's clear that patients want and need to get results more quickly than traditional models can accommodate. "Even though we have a result, it can take months to get a family into the clinic … so there have to be strategies to improve that — to return, but also to frame [results] in a way that is helpful to families," he said.
For My46, the UW team developed three different main modes of use that might be clinically implementable. In an adjunct model, results would still be still returned in a traditional manner — where patients actually have to meet with someone either in person or over the phone — with the website serving mainly as an educational add-on that can be used "before, during, or after a clinical encounter to provide general genetics information and/or information about a specific trait."
Bamshad said that this can offer some added efficiency, and help clinicians focus more on interpretation and medical management, but not much.
On the other end of the spectrum, the self-guided implementation of My46 allows a family to have significant autonomy in terms of what results they want to access, even independently of their clinical care provider.
Each result is accompanied by a recommendation for further evaluation. "However, families/patients are provided more latitude such that mandatory evaluation is required only for positive results of moderate and high priority," Bamshad and his coauthors wrote.
A middle road between self-guided and adjunct is what the group defines as an "assisted model" in which the physician or provider gets to review results and be involved in their communication to a patient or family.
"People are concerned about going to a completely self-guided model … so we put in this review step," Bamshad said.
This still means that results are physically accessible to a patient through My46, but in the context of a care provider being aware of that result, and typically being aware first, Bamshad explained.
"That's probably the model, after speaking with a lot of clinicians, that will be the most comfortable for them to use," he said. "And it provides scalability that is still reasonable, and much greater than an adjunct model, but not as high as with a full self-guided model."
Moving forward, Bamshad and his coauthors recognize that it will be important to continue to study My46, especially the extent to which receiving results through the tool, or similar systems, affects health-related outcomes or patient wellbeing.
Results from the group's NHGRI-funded study, which followed a group of about 150 families using surveys and interviews, should help shed some light on that.
"We would have liked to see a larger cohort, but each family completed a number of surveys and interviews, so the data is actually quite extensive," Bamshad said.
Moving forward, he mentioned two new ways that UW is planning to implement and continue studying My46.
One project is returning clinical results to families who are sequenced under suspicion of carrying Fragile X syndrome.
"95 percent of these results are negative," Bamshad said, "so rather than return those by way of a counsellor, either face to face or by phone, My46 provides an easy way to return all of those negatives … And families with questions still have the option to meet with a counsellor if they want."
Secondly, the UW team is going to use My46 to return results from CLIA-certified whole-exome sequencing in conjunction with what the researchers hope will be growing use of another web tool they developed called MyGene2.
MyGene2 is a sharing platform for health information and genetic data aimed at facilitating gene discovery, genotype-phenotype understanding, and even diagnoses, among families with suspected Mendelian disorders.
"There are tens of thousands of exomes sequenced both in research and clinical service, with no diagnoses, and no effective way to share that data," Bamshad said.
Unlike other tools, where users can match but not search data, Bamshad called MyGene2 a "family-facing, public, and searchable" system.
My46 will allow UW to offer exome sequencing through a CLIA lab, and return results to them that they can then share through MyGene2.
"This is the way the world is headed, we think inevitably, so we are trying to push the field to think like this," Bamshad said.
"However," he added, "it's going to take a real cultural change in the way care providers think about their relationship to a family," with their role shifting away from being gatekeepers in the process of results return to more of partnership.