NEW YORK (GenomeWeb) – Researchers from the University of Washington have attempted to quantify whether returning incidental findings from exome sequencing tests is cost effective and found that at least for certain indications and certain findings it very well may be.
The team conducted the study, which was published online in Genetics in Medicine last week, as part of its NEXT Medicine clinical trial where it is investigating the use of exome sequencing in patients referred for genetic testing for colorectal cancer. The trial is one of the National Human Genome Research Institute-funded Clinical Sequencing Exploratory Research projects.
David Veenstra, a professor and associate director of the Pharmaceutical Outcomes Research Program at UW, told GenomeWeb that while the results were preliminary and based on modeling as opposed to actual patient data, it appears that returning incidental findings is likely cost effective. "It is probably not going to save money, and may cause some increase in cost," he added, "but the value you get in terms of improving life expectancy and quality of life is worth it."
To do the study, the researchers focused on two different types of patients that might be prescribed exome sequencing for a clinical indication — cardiomyopathy patients and colorectal cancer patients — as well as generally healthy adults receiving exome sequencing as a screening test because family history indicates a specific disease risk.
They next created a model to evaluate incidental findings from the American College of Medical Genetics' list of 56 genes that would be found in patients from each of those hypothetical cohorts and likely scenarios for the impact of those results on future care, healthcare costs, quality of life, and life expectancy.
The researchers used previously published cost effectiveness data from genetic testing that was available for colorectal cancer patients to model the impacts. For cardiomyopathy patients, for which existing analyses did not exist, they created a disease simulation model.
In addition, instead of creating separate models for each incidental finding in each cohort, they focused on seven of the 24 conditions represented in the 56-gene list. Those seven conditions were thought to represent 95 percent of incidental findings. The group evaluated the incremental costs and quality-adjusted life years saved by returning results related to each of the seven conditions.
After creating models for the individual cost and quality of life years for each of those incidental findings, they incorporated the prevalence of identifying and returning those results.
For individuals in the cardiomyopathy and colorectal cancer disease cohorts, findings in ACMG genes that related to those conditions were not considered incidental but rather a primary finding since it is related to the patient's condition. Therefore, those were not taken into consideration.
The group found that returning incidental findings to cardiomyopathy patients, colorectal patients, or healthy individuals would increase costs by $896,000, $2.9 million, and $3.9 million, respectively, while increasing quality-adjusted life years by 20, 25.4, and 67 years, respectively. Overall, that would result in an incremental cost-effectiveness ratio (ICER) of $44,800, $115,020, and $58,600, respectively, where the ICER is defined as the difference in cost divided by the difference in quality-adjusted life years.
The group did not include the cost of sequencing itself in its projections, since that cost was assumed as part of the diagnostic workup. But if it is included for healthy patients, then the ICER jumps to $133,400.
Veenstra said that he was surprised that returning incidental findings was "somewhat in the ballpark of being cost effective."
One notable finding was the differences between the individuals receiving sequencing because of a specific indication versus healthy individuals. "Returning incidental findings to someone who is sick and life expectancy is not high; the possibility of them benefitting is not as high," Veenstra said. Although, he added, that the family may benefit from such results. However, for some indications, like Lynch syndrome, it is likely that the colorectal cancer patients' family members will have already been tested for those variants.
For otherwise healthy individuals, the results seem to suggest that in the long run there may be more of an opportunity to benefit from the information, but in order to use exome sequencing for primary screening, "there are huge questions that have to be answered," Veenstra said. For instance, he said, the evidence bar for what constitutes a pathogenic variant that should be returned has to be set very high. In addition, since there would be the possibility of screening so many more people, the approach "has to be not just cost effective, but highly cost effective."
Veenstra said that he thinks the study will serve as a "stake in the ground" to enable conversations about sequencing, incidental findings, and their impacts. "Instead of hand waving, we now have some numbers and ranges that we can talk about," he said, which will help "facilitate conversations between test developers and reimbursement folks."
Previously, he said, opinions about the impact of returning incidental findings were on two opposite sides of a spectrum, with one side claiming that returning such results would bankrupt the healthcare system and the other arguing that it would save money.
The next steps will be to gather more real-world data in terms of what actions patients and providers actually take based on incidental findings and then to update the analysis based on that data, Veenstra said. Additionally, it will be important to consider other incidental findings that various groups are returning. For instance, he said, UW now has a list of up to 114 incidental findings that can be returned.
Veenstra added that by no means will this study be the end of cost-effectiveness studies, but rather it should serve as a starting point. There are still many more scenarios to take into consideration. For instance, the study did not consider pediatric patients for whom exome sequencing is ordered to diagnose a developmental delay disorder — a scenario that might even see greater benefit, Veenstra said, since the patient is young.
"For the particular types of patients, we have to think [about] how much would that be a benefit. What's their prognosis? That's something we need to be thoughtful on," he said.
Over the next few years, Veenstra said that data from all the CSER sites could be pooled to create better models for various patient populations.