Estimating Total Costs When Genetic Tests Must Be Retested

INVITAE, A GENETIC TESTING COMPANY IN San Francisco, has begun a retest program involving 50,000 patients. Such a large retest effort is without precedent in the still-nascent genetic testing marketplace.

Clinical laboratories and genetic testing companies commonly find that, in daily operations, a batch of samples produced unreliable or inaccurate results. These discoveries are made as part of every lab’s quality control procedures and typically these discoveries involve tens or hundreds of specimens. Physicians understand this aspect of lab testing.

But when the numbers reach into the tens of thousands, medical directors at other genetic testing labs take notice to learn how to respond effectively if their lab has a similar problem.

Invitae’s retesting effort comes after it learned in July that the materials for a rare mutation associated with inherited cancer were omitted from a new assay version of its genetic tests that it developed last year. From September 2016, until the systemic error was identified in July 2017, Invitae reported erroneous genetic test results.

One Mutation Omitted

These genetic assays did not test for the Boland inversion mutation on the MSH2 gene. This gene is associated with Lynch syndrome, which is also known as hereditary nonpolyposis colorectal cancer. Late on Friday, Turna Ray reported for GenomeWeb that Invitae’s CEO Sean George estimated that 2 to 15 patients had gotten a false-negative result. To be certain that it identifies all possible patients who may have received a false-negative result, Invitae said it would retest 50,000 patients, Ray reported.

The number 50,000 may be about right, according to Richard Faherty, a consultant with RLF Consulting LLC and formerly with BioReference Laboratories and its GeneDx division. “There is another way to look at Invitae’s accession volume and test menu,” he said. “First, consider the number of tests on the Invitae test menu that includes testing for MSH2 and therefore the Boland inversion coverage. There are at least 18 such tests.

Extrapolating Test Volume

“We don’t know Invitae’s test-ordering mix,” Faherty explained. “But during the company’s fourth quarter earnings conference call, there was a discussion about the number of tests that Invitae ran last year and that number was 60,000.

“From that discussion, we know that about 80% of those tests were cancer tests and that the vast majority of those cancer tests were for hereditary breast and ovarian cancer,” he added. “We can apply that proportion to test volume to give us some idea about the numbers,” he added.

“This approach generates an estimate of 45,000 patients that Invitae will probably need to retest, and that number is close to the 50,000 Invitae reported,” he noted. “Now, can we estimate how much all the retesting might cost?

“Invitae told GenomeWeb that the cost to retest is about $10 per test—a cost most lab directors would consider to be a low estimate,” commented Faherty. “That may be possible, depending on what technology the company will use. But that cost of $500,000 would be the materials only and probably does not include staff time to run the test and analyze the results or to contact doctors and patients to discuss the need to retest and the results of each test.”

Faherty added an important point about patients’ anxiety. “We have to assume that many of these 50,000 patients or their clinicians will ask about the reliability of the retest and what that level of reliability means for them,” Faherty added. “All that anxiety might mean additional time on the phone for Invitae’s genetic counselors and other staff, and that also costs money.”

Estimating Retesting Costs

One lab expert familiar with a large retesting program estimated that it might cost as much as $60 per sample. “There are several methods—such as multiplex ligation-dependent probe amplification and breakpoint PCR—both of which are high-throughput assays that a lab could run for about $35 a sample in reagents,” the expert said. “When you add the expense of labor and reporting, costs start to approach $50 per sample.

“I would assume you would need to dedicate a team to do this work because 45,000 to 50,000 samples is no small undertaking,” she added. “All of these calculations do not include the cost of recontacting patients and having to re-isolate DNA on a percentage of them. That would easily add $5 to the per-sample cost.

“Considering all of these factors, I estimate that a lab would be hard pressed to do this retesting for less than $60 a sample,” she stated. At $60 per sample for 50,000 samples, the cost climbs to $3 million.

“While $10 to $60 per retest seems reasonable, other experts have suggested that the cost to retest could climb as high as $250 per test,” Faherty added. “If that’s true, then Invitae would have a much higher total of as much as $12.5 million just for retesting and not including the costs for contacting doctors and patients.”

Contact Richard Faherty at

Which Invitae Genetic Assays Address MSH2 Mutation?

FROM THE INVITAE TEST MENU, it is possible to estimate the number of assays that would test for the presence of MSH2. There are 18 such genetic tests as follows:

  1. Invitae Constitutional Mismatch Repair-Deficiency Panel
  2. Invitae Lynch Syndrome Panel
  3. Invitae Prostate Cancer Panel
  4. Invitae Myelodysplastic Syndrome/Leukemia Panel
  5. Invitae Pediatric Hematologic Malignancies Panel
  6. Invitae Gastric Cancer Panel
  7. Invitae Pancreatic Cancer Panel
  8. Invitae Colorectal Cancer Guidelines-Based Panel
  9. Invitae Pediatric Nervous System/Brain Tumors Panel
  10. Invitae Colorectal Cancer Panel
  11. Invitae Renal/Urinary Tract Cancers Panel
  12. Invitae Breast and Gyn Cancers Guidelines-Based Panel
  13. Invitae Common Hereditary Cancers Panel (Breast, Gyn, GI)
  14. Invitae Sarcoma Panel
  15. Invitae Breast and Gyn Cancers Panel
  16. Invitae Nervous System/Brain Cancer Panel
  17. Invitae Pediatric Solid Tumors Panel
  18. Invitae Multi-Cancer Panel


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