This is the fourth in a series of profiles of projects awarded NHGRI grants to develop policy guidelines on how and when to disclose secondary information to the subjects of genomic research studies. We previously profiled three other projects: two underway at Columbia University and another at the University of Washington.
A study underway at Boston Children's Hospital is investigating how the preferences of parents can inform a choice-driven and ethical system for returning secondary findings of genomic sequencing studies of young children.
The project, led by Boston Children's' Ingrid Holm, is combining a series of cognitive interviews — to better understand subjects' preferences and decision making in choosing what results to receive from their children's sequencing data—with a study tracking the experiences of families who actually go through the process of receiving results.
Holm's study is one of seven projects funded in a $5.7 million program launched last year by the National Human Genome Research Institute to create policy guidelines and tools for disclosing secondary information to the subjects of genomic research studies.
While some of the funded studies are focused on actionability, and what can and should be returned to patients according to outside experts, Holm's project is exploring whether participant preferences themselves can reliably guide the return of individual research results.
"The project is in part using hypothetical results trying to understand how people think about their preferences for what type of results they would want back," Holm told Clinical Sequencing News.
"The interview portion gives us an opportunity to push the envelope in terms looking at different possibilities," she said. "Then we'll be looking to see whether people benefit from having choices, and [whether] they understand the implications of the things that they choose."
For the interview section of the study, Holm explained that the researchers are recruiting families from BCH for a two-hour conversation in which researchers go through educational materials on genetic results and get feedback from participants on whether they understand or not. Then subjects are offered different kinds of possible results, and are asked what they might want to receive, as well as what is important to them in deciding what they may or may not want back.
Because the group is looking at parents, Holm said there are some additional ethical issues that can further complicate things. "For example, traditionally in genetics we never return results about an adult onset condition where there's nothing you can do to intervene in childhood until the person turns 18 and has the ability to choose," she said.
"So then we have to explore those issues with parents too and see if they understand that; and also talk to adolescents and younger kids about that to see if they understand that and if this framework of autonomy really makes sense."
So far the researchers have conducted fewer than 10 interviews, Holm said. They plan to do a total of 20 to 30 within the hospital.
"We're trying to develop a framework," Holm said, "because eventually we want [to create] some sort of a preference-setting tool that’s easy to use and understand."
The researchers plan to use that framework to develop a web-based tool that they can use to profile a larger number of parents with children — several hundred — recruited online.
Holm explained that after the interview portion of her study, she and her colleagues will move on to actually go through the process of returning results. "We'll use what we've learned about preferences to give people an opportunity to say what kind of results they want, and then return those within the framework of their preference and look at the outcomes," Holm said.
The team will look at whether subjects' families feel they got the results they expected to get, as well as what they do with the information, and how it affects them.
Holm said the researchers plan to return results to a few hundred families participating in sequencing research through the hospital's The Gene Partnership project, which is gearing up to begin sequencing research on diseases like autism, congenital heart disease, epilepsy, and a variety of monogenic disorders.
Holm's project abstract describes TGP as a pediatric research registry combining genetic banking, access to electronic medical records, and scalable computer-based systems to ascertain preferences for return of results from the parents of research participants and, ultimately, to return those results.
According to Holm's project description, participants in the study will be randomized to one of three methods to set their preferences: an all-or-nothing choice, a checklist of types of results, or an interactive educational and checklist tool.
Other projects funded in the NHGRI's program have taken different approaches to the task of creating best practices for returning secondary results from genomic research. Several are delving not only into patient preferences, but also tackling the issue from the perspective of investigators.
Holm's project is centered more sharply on the participant's side — assuming that all ethically returnable results should be returned, what do people really want, and how can they best decide what that is?
Holm said ideally she hopes preference-based guidelines that emerge from the project will also be relevant for clinical sequencing. "My hope is that this concept of people being able to say what they do and don't want might be something that would be translatable."
"The idea is how to return results to participants in a way that is consistent with what they would like to hear about," she said.
The study is funded for three years, Holm said, but is likely to continue beyond that period.