This is the second 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 another project underway at Columbia University.
Researchers at Columbia University are tracking patients' experiences after receiving secondary findings from genome sequencing studies in order to inform recommendations for better consent practices in sequencing research.
The study, led by Wendy Chung, began last September as one of seven projects funded in a $5.7 million program by the National Human Genome Research Institute aimed at creating policy guidelines on how and when to disclose secondary information to the subjects of genomic research studies.
The NHGRI projects range from ethics- and psychology-based studies — like another Columbia project, led by Paul Appelbaum, that is using surveys to query researchers and patients on how they think the consent process should work (CSN 5/30/2012) — to hands-on studies like Chung's, which are actually returning results to patients. The seven teams together make up an NHGRI consortium on informed consent for return of results.
"Now that many of us are doing whole-exome, whole-genome analysis, though we all started out our studies intent on trying to understand one disease, when you look at all genes … you sort of have collateral damage," Chung told Clinical Sequencing News.
"The question is, when you start coming up with all this other information, if you happen to just stumble upon something that would have implications for one of your participant's health — in particular if there were some actionable intervention, a step you could take to potentially prevent a bad outcome — what's the obligation of the researchers to try and contact participants about that, to warn them about this?" she said.
"And reciprocally, do participants really want to know that information in the first place, and how much?"
Chung and her team plan to recruit about 180 patients from completed exome sequencing studies she has conducted on a range of genetic conditions from cancers to common diseases like diabetes.
The researchers plan to ask these subjects whether they would want to receive secondary findings from their exome data if available and, if so, what kind of data. The team will then counsel the participants and release the desired results to them, and will follow up over one year with surveys and interviews intended to tease out how the sequencing information affects patients' lives and relationships. The cohort will be matched with 180 control subjects who do not have exome sequencing data available for return but who will be treated to the same questions regarding what results they might want.
At the same time, the group is interviewing and surveying researchers to try to understand broadly how they are thinking about approaching consent for return of secondary findings and how the burden of the process can be lifted for both researchers and participants.
"When you start thinking about doing this, the pushback from researchers is, 'I wasn’t given resources to do this, I don't have the expertise to do this – maybe I know my gene, but I don’t know all genes,'" Chung said. If results are to be returned, she said, they also have to be confirmed in a CLIA laboratory, adding significant time and effort.
Chung said her team has also found through its initial surveys that the consent process itself can be a burden for both researchers and participants.
"These things can be anywhere from seven to 20 pages long and you almost need a legal degree to understand what some of this means even though its supposed to be written at a 5th grade level," she said. "So one of the things we've heard from everyone is that we don't want to overburden people with the consenting process for sequencing results."
Chung said her team thinks the best approach to simplifying the process may be to start with the most basic issue of consent — whether a patient wants any results at all — and then tackle finer-tuned issues in a menu-like format.
"I think the trick is going to … come down to explaining the idea that there could be results generated that have implications for your health – do you want to know about that, yes or no, and then if the answer is yes, there may be finer granularity," she said.
Chung and her team will ask subjects who have previously participated in whole-exome sequencing research studies whether they would like to have secondary data returned to them. If they do, the researchers will give them a menu of possible results along with their potential implications.
The menu will cover a range of what Chung described as levels of actionability — grouping different kinds of results by how closely they are linked to legitimate medical or health interventions.
Chung said one menu section might include carrier status for recessive conditions with reproductive implications; another would be pharmacogenetic markers; and another, ancestry information.
"We're going down in terms of actionability from things like Lynch syndrome to things like Huntington's disease or Alzheimer's — things that are not necessarily medically actionable, but some people have preferences in terms of what some have called 'personal actionability,' which is just being able to mentally prepare and be ready for those things," she said.
The team will register subjects' preferences and will go back to the whole-exome data collected for each participant and see if they have any results that fit into what they've selected from this menu, validating any results through a CLIA lab using a fresh sample, Chung added.
Participants will go through both pre- and post-test counseling, and the researchers will follow them for a year with a set of serial surveys and interviews.
"We want to understand at the end of the day whether [patients were] happy with their decision to get results," Chung said. "Did they understand their results? How have they used that information for their own personal health? How have they communicated that information with providers or family members? And has it had a good effect in terms of family relationships, or has if backfired in some way?"
"We're trying to gain some experience on what the best and worst of this could be, and how do we keep the good things going, and avoid any bad things," she said.
Chung said that while the cohort will be an oversampling of people who have a family history or personal history of some disease — because those have been the subject of her exome sequencing research — she is purposely drawing from a range of different diseases.
"You can imagine you come to the table with different psychological baggage depending on what's been in your family and we really wanted people with different levels of anxieties and levels of sophistication about genetic information," she said.
Chung's study received about $400,000 in direct funding per year for three years under the NHGRI program. At this point, the team has invited most of the participants and has done baseline questionnaires. Many subjects have already had pretest counseling, she said, and a few have received results and gone through post-test counseling as well.
She noted that there already appears to be a wide range in participants' desire for information, mirrored by an equally large range in the opinions of researchers on what should be returned.
"Some patients want to know maybe only pharmacogenetic information, which they consider relatively safe," Chung said. "We've already seen that some people kind of live in that safe zone. But there are also patients who literally say, 'Give me everything. If you could give me a hard drive with my data, I want the whole thing.'"
"Researchers are also in that very broad range," she said. "Some would say, 'It's not a burden to me if I don't have to do anything for the patient; I would send them the files and they could analyze it to their heart's content. It's their information.' Other researchers are very concerned, in a good way, about wanting patients to [only] get information that is useful to them."
Late last year, NHGRI also funded of a group of projects evaluating the impact of clinical sequencing and return of incidental findings, called the Clinical Sequencing Exploratory Research program. These studies all involve three sections, the third of which is focused on return of "incidental," or secondary, findings. (CSN 12/7/2011)
Chung said the return of results consortium teams are working closely with researchers from each of the CSER study's "project-threes." The groups had a joint meeting this spring, she said, aimed at sharing approaches and "trying to make sure we're not duplicating efforts."