NEW YORK (GenomeWeb) – Applying whole-exome sequencing early in difficult-to-diagnose patients with intellectual disability could lead to substantial cost savings by preventing further diagnostic tests and procedures, regardless of whether the patient receives a diagnosis or not, according to a pilot study by researchers at the Utrecht University Medical Center in the Netherlands.
According to the cost analysis, published yesterday in Genetics in Medicine, the early use of whole-exome sequencing could save an average of $3,500 in patients who obtain a diagnosis and $1,700 in patients who do not, by preventing further genetic and metabolic tests. Savings might be even greater if other types of prevented diagnostic tests were included in the analysis.
The results suggest that whole-exome sequencing "should be implemented early in clinical diagnostic centers with similar patient populations," the researchers concluded.
For their study, the team, led by senior authors Gerardus Frederix and Gijs van Haaften, randomly chose 17 patients who received parent-patient trio whole-exome sequencing at the Sylvia Tóth Center in Utrecht, a multidisciplinary center that specializes in diagnosing children with intellectual disability. Prior to being admitted to the center in 2011, these patients had been evaluated by a number of iterative tests but had not received a diagnosis.
In five of the patients, or about 30 percent, the exome test provided a molecular diagnosis. Using data from hospital information systems and patient records, the researchers then tallied all diagnostics-related costs for individual patients that could be saved if whole-exome sequencing was used earlier in the process, looking separately at the diagnosed and undiagnosed patient groups.
For both groups, they assumed that exome sequencing would replace all genetic tests except array comparative genomic hybridization and SNP arrays, which would still be performed to exclude copy number variants. For the diagnosed patients only, exome sequencing would also replace all metabolic assessments, which would still be carried out in the undiagnosed patients. In a separate assessment, they also included a 50 percent cost reduction from other diagnostic procedures and associated healthcare visits that could be prevented.
Overall, patients were on a "diagnostic trajectory" for an average of almost seven years until they received whole-exome sequencing, during which time they incurred diagnostics-related costs from healthcare visits, imaging, genetics, metabolic measurements, biochemical tests, and patient day admissions. These costs totaled about $16,400 per patient, ranging from $6,300 to $48,000, of which genetic test costs accounted for 42 percent.
Patients received seven genetic tests on average, most of them single-gene tests, and six metabolic tests, as well as 16 imaging tests, mostly X-rays and MRIs. As part of their diagnostic journey, each had 61 visits with healthcare professionals on average.
In those patients where exome sequencing rendered a genetic diagnosis, putting the exome test in front could have saved $5,000 on average in genetic tests, ranging from $0 to $10,700, and $2,500 in metabolic tests, ranging from $2,200 to $2,900, that would have become unnecessary.
Starting with the exome test in patients where it did not lead to a genetic diagnosis would have saved an average of $5,700, ranging from $890 to $18,700, in unnecessary genetic tests.
Assuming a cost of $4,000 for the trio exome sequencing test, using exome sequencing first would save an average of $3,500 in diagnosed and $1,700 in undiagnosed patients, the researchers calculated.
In addition, exome sequencing could save $1,700 in diagnosed and $4,300 in undiagnosed patients, they estimated, from a 50 percent reduction in healthcare visits, imaging, biochemical tests, and patient day admissions that would become dispensable. However, the size of these additional savings is "debatable," they wrote, and might be lower for undiagnosed patients.
Despite the small number of patients included in the study, which prevents definite conclusions, it shows that implementing whole-exome sequencing is "a relevant and cost-efficient option in patient diagnostics," the researchers wrote, and provides information that is "crucial for centers considering implementation of whole-exome sequencing."