NEW YORK (GenomeWeb) – In the wrongful death lawsuit filed by Amy Williams against Quest Diagnostics and subsidiary Athena Diagnostics, the companies this week filed a notice requesting the case be moved from the South Carolina Court of Common Pleas for Richland County to the US District Court in the District of South Carolina.
Also, in answers to written questions (or interrogatories) from the plaintiff, Quest and Athena said that the doctors treating Williams' deceased son "may be liable in whole or in part to the plaintiff or to the defendants."
Senior US District Judge Margaret Seymour is presiding over the still-pending case. Responses to interrogatories are not allegations by the defendants, which have yet to respond to the plaintiff's complaint. Quest did not provide comment for this article.
Bradford Cranshaw, representing the plaintiff, said he doesn't plan on challenging Quest and Athena's notice to remove the case to federal district court. "We are pleased to tell the story wherever the court will allow," Cranshaw told GenomeWeb.
The lawsuit deals with the circumstances surrounding the death of Christian Millare, who passed away from a seizure at the age of two in January 2008. Christian's mother, Williams, filed suit in February accusing Athena of failing to follow federal lab regulations outlined in Clinical Laboratory Improvement Amendments when testing her son for mutations in the SCN1A gene and reporting the results. Williams alleges Athena misclassified the detected mutation as a variant of unknown significance (VUS) when two papers — published before Athena issued Christian's June 2007 test report — had identified the same mutation in another patient who had epileptic encephalopathy.
Among the authors of one of those papers is Sat Dev Batish, who then was and still is Athena's chief director of genetics. Also, a patent that Australian firm Bionomics licensed to Athena for the development of its SCN1A test lists the mutation (1237T>A) that Christian had as one that "disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype."
Mutations in SCN1A are well known in the literature to cause Dravet syndrome, a severe form of epilepsy that impacts one in 21,000 infants. The Dravet Syndrome Foundation estimates that 80 percent of patients will have an SCN1A mutation.
Christian, under the care of neurologists and geneticists specializing in mitochondrial disorders, had received a battery of tests in an effort to pin down the cause of his seizures. After looking at Christian's clinical and metabolic features, and evaluating enzymes in his tissues, doctors thought Christian's seizures may be due to a mitochondrial disorder.
For his seizures, doctors had prescribed the sodium channel-blocking drugs carbamazepine, oxcarbazepine, and lamotrigine. These are standard treatments for epileptic seizures, but they weren't helping Christian. Studies show that sodium channel-blocking drugs worsen seizures in Dravet patients.
In response to the plaintiff's questions, Quest and Athena said that Christian's doctors may be liable because, based on the 2007 SCN1A VUS result from Athena, Christian's doctors failed to test his parents in order to rule out Dravet Syndrome and continued to treat him with sodium channel blocking medications "when they apparently had no beneficial effect on [his] symptoms."
In her complaint, Williams identifies Timothy Livingston, then employed at University of South Carolina Medical School, as Christian's treating neurologist who prescribed sodium channel blocking agents. The SCN1A genetic test was ordered "at the direction of" Christian's clinical geneticists John Shoffner and Frances Kendall in January 2007, while they were at Horizon Molecular Medicine in Atlanta, according to the complaint. Shoffner has managed patients with mitochondrial disorder for nearly 30 years and identified some of the first gene mutations that cause such diseases. Christian's SCN1A test report indicates Athena should have issued the report to Shoffner.
Shoffner and Kendall started Horizon Molecular Medicine, but they dissolved the practice in December 2007, while Christian was a patient there. At the start of 2008, Shoffner launched Medical Neurogenetics, which purchased Horizon Molecular Medicine's assets, including lab results, patients' charts, and customer lists, according to a lawsuit involving the transfer of these assets.
Christian died in January 5, 2008. Before he passed and for years after, Williams claims that neither the lab nor the doctors told her about Christian's 2007 SCN1A genetic test report.
Meanwhile, Medical Neurogenetics, now called MNG Laboratories, provides biochemical testing and next-generation sequencing for neurological disorders, such as epilepsy. Shoffner was CEO and subsequently chief medical officer, but has recently retired from the executive team.
Based on publicly available information, Kendall is heading up VMP, a company focused on treating patients with rare genetic, metabolic, and mitochondrial disorders. Livingston is practicing in North Carolina.
While Williams' lawyers have set out to prove that Athena was negligent and that negligence caused Christian's death, it wasn't unexpected that Quest and Athena would turn their attention to Christian's doctors. "Look for the defendant down the road to lay off blame on the doctor," John Conley, a law professor at the University of North Carolina and an IP and biotech law expert, told GenomeWeb last week.
Williams previously told GenomeWeb that she hopes the lawsuit results in a change in the regulations so labs are held more accountable for the results they report. Many experts in the genomics field agree. Russ Altman, director of the biomedical informatics program at Stanford University Medical School, said there needs to be a robust infrastructure for tracking the latest information on variants, as well as standards for determining when a variant is actionable, interpretable, or truly of unknown significance.
Altman, since 2000, has led the development of PharmGKB, a publicly available repository of genetic variants related to drug response. As such, he is very supportive of government-funded data sharing efforts, such as ClinVar, an archival database of genomic variants, and ClinGen, which experts are building into an authoritative resource on the clinical relevance of genes and variants. In addition to industry standards, Altman acknowledged that the US Food and Drug Administration may need to step in to ensure that doctors are getting good variant interpretations.
"I am sure that non-genetic specialists ordering these tests will rely on the report provided by the [test] provider, and it will be very hard to ask them to understand and re-interpret the raw data," said Altman. "So, their liability should extend to reasonable expectations for ordering the tests, and reasonable interpretations of the test results, using the report that is provided. The test provider really should bear significant burden in ensuring that the reports are as accurate as possible." Altman is an attending physician in Menlo Park, California, but also serves as a scientific advisor for Personalis, a company that sequences patients' exomes and genomes and interprets the data for researchers and clinicians.
As previously reported by GenomeWeb, Williams v Quest/Athena brings into focus the challenges for labs, doctors, and patients as genetic testing technologies are getting better at detecting variants, while the policies and standards for classifying what those markers mean in the context of disease and how they should be communicated to doctors and patients are still in flux.
More and more experts like Altman hope that public data repositories and a community approach to classifying variants will ease the uncertainty in variant classification, although some labs are not eager to share variant data and believe public repositories to be a liability. Others have suggested that the College of American Pathologists in accrediting labs and the Centers for Medicare & Medicaid Services in enforcing CLIA should strengthen oversight of the variant classification process.
Christian died eight years ago, but the lawsuit comes during a period of rapid expansion for the genetic testing industry. The global genetic testing market is projected to grow from $3 billion in 2014 to more than $6 billion by 2022. Healthcare technology firm NextGxDx estimates there are approximately 60,000 genetic testing products currently marketed in the US, and has noted significant growth in next-generation sequencing panel tests in recent months.
Given the growth in the number and in the complexity of marketed tests, many have wondered how doctors with limited genetics knowhow will keep up and whether they'll face more lawsuits if they order the wrong test, misinterpret results, or fail to explore a VUS that might be critical for a patient.
Gary Marchant, a law professor at Arizona State University, is tracking medical liability in the genomics era as part of an NIH-funded project and has noted a slight increase in genetic-testing related lawsuits but not as much as he had expected. People are suing doctors in situations where it's clear they made a mistake in dealing with genetic test results, Marchant said, but cases like Williams v Quest/Athena, that raise questions about the judgment of the lab or the doctor, are more difficult to litigate.
Plaintiffs' lawyers seem hesitant to take on such cases because they lack the genetics expertise and they are uncertain how juries will respond given the evolving nature of the field. "There's this doctrine in medicine that mistakes happen," Marchant said. "And just because a mistake happened doesn't mean there is liability. It's only when you cross a line of being so clearly wrong in what you did that the jurors will punish a doctor or lab."
Accepting that the practice of medicine involves science and art, juries have historically been sympathetic to doctors. But according to Marchant's research so far, juries have been unpredictable in their verdicts in genetic testing related lawsuits.
For example, a Connecticut woman with breast cancer in the family sued her doctor for failing to tell her that her family history put her at increased genetic risk of ovarian cancer, and in 2012 the state supreme court upheld a $4 million jury verdict. Also in 2012, an Oregon couple that sued their doctors and hospital for inaccurately interpreting prenatal testing results received $3 million in damages. However, a Montana jury in February ruled against a mother seeking $2.5 million in damages from doctors she said failed to diagnose her unborn child's cystic fibrosis.
The uptick in lawsuits is perhaps part of the growing pains for the genomic testing industry. New technologies have an unsettling effect on the healthcare landscape, with some providers adopting the technology early and others deciding to take it up too late. "People have to change what they do and learn on the fly," Marchant said. "There is shifting knowledge in the scientific literature, but also in the training, and that is exactly the recipe for liability."
Although the law now gives people the right to access their own lab results, when Christian received genetic testing, doctors didn't usually share results with patients. And if variant classification is an evolving science today, it was even more so eight years ago.
Athena launched a program in 2010 specifically to tackle VUS, and "save physicians time and provide them with enhanced test reports." In a 2011 post on its website, the lab highlighted that it had studied more than 1,000 variants, and conclusively classified 148 as benign and 28 as pathogenic.
"Hindsight is always 100 percent," Marchant said. "In this case, there certainly seems to be some evidence in retrospect that things should have been done differently. And the question is what difference would that have had on the outcome?"