Assessing the Value for Money of Using Genome Sequencing in Child Health

If you have a child with a neurodevelopmental condition, such as autism, epilepsy, or unexplained developmental delay, finding a genetic cause for his/her condition can bring peace of mind and avoid what seems like an endless cycle of medical evaluations and tests. The application of next generation sequencing (NGS) methods, including sequencing the protein-coding region of DNA (i.e., exome sequencing [ES]), and sequencing the entire genome (i.e., whole genome sequencing [WGS]), can often identify more genetic causes of these disorders than traditional genetic testing (chromosomal microarray [CMA], single gene, and panel tests) and can also shorten the diagnostic journey. Although both NGS and traditional testing show clinical utility, it is also important to evaluate where to position NGS within a patient’s diagnostic pathway to optimize that patient’s care, and to maximize value for money, where value for money considers the health benefits returned for every dollar invested above and beyond the current standard of care.

On October 15, Dr. Wendy Ungar of the Hospital for Sick Children and the University of Toronto presented a CDC webinar on economic evaluations of ES and WGS for children with certain neurodevelopmental conditions. NGS requires special equipment, computing and data storage capability, and skilled bioinformatics specialists. Using microcosting to measure the resources and labor associated with each step of a laboratory pathway and assign unit prices, the research unit at Technology Assessment at Sick Kids (TASK) in Toronto investigated the costs of several ES and WGS platforms for children with autism. With more than 60 separate cost items for each platform, the cost of ES was found to be US$1,486—two-fifths less than $2,513 for WGS. When conducting sequencing in children, it’s useful to sequence both biological parents at the same time as the child—a trio sequence. Trio ES in families affected by autism cost $3,054 compared to $4,917 for trio WGS. The researchers found that ES performed after CMA had failed to return a result cost $4,499 per additional diagnosis relative to only CMA. If CMA were replaced with ES for all children, the additional cost per diagnosis relative to that of CMA would be $10,128. If instead WGS were used in place of CMA as a first test, the cost per diagnosis achieved was lower—$8,089 per new diagnosis—although that is still more than the sequence of CMA followed by ES, $4,499.

In another study, a team at the Ontario Ministry of Health compared genetic testing strategies for children with unexplained developmental disabilities or multiple congenital anomalies who typically experience protracted diagnostic odysseys with many sequential tests. When ES was performed as a second tier test after standard CMA testing had failed to return a result, it saved $1,819 per patient because single gene tests and gene panels could be avoided. In addition, a diagnosis was more likely and could be achieved sooner. Performing ES together with CMA as first tier genetic tests gave the highest probability of a diagnosis, but the savings were not as great: $1,348 per patient. This study was part of a comprehensive health technology assessment that contributed to a decision to fund ES for children with unexplained developmental disabilities or multiple congenital anomalies in Ontario, Canada. Performing these types of comparative economic evaluations in different patient populations can inform funding and acquisition decisions as NGS methods evolve and diffuse into clinical practice.

These analyses demonstrated that although new genetic technologies have relatively high prices, albeit decreasing over time, they may provide good value for money for specific patient groups because of their higher diagnostic yields. That is true both overall for NGS and, in some settings, for WGS relative to ES. Also, lower cost does not necessarily mean more cost-effective. The net cost and value of genome sequencing strategies depend on the context; the order in which sequencing tests are positioned in diagnostic pathways matters.