NEW YORK (GenomeWeb) – Lawyers representing Amy Williams have countered that a federal district court should not dismiss her wrongful death lawsuit against Quest Diagnostics and subsidiary Athena Diagnostics because she did not know their lab had performed a critical genetic test for her now deceased son until 2014.
In April, Quest and Athena asked the US District Court in the District of South Carolina to dismiss the wrongful death lawsuit because the six-year time limit for medical malpractice claims has expired since Athena issued a 2007 genetic test report for Williams' son, Christian Millare, who died in January 2008. Tort cases in the US rarely go to trial, and Quest and Athena want to ensure that this case doesn't.
"Defendants in cases like this don't want it to go to trial and they don't want it to go to a jury, which is completely sensible because both trials and juries are expensive and unpredictable," said Hank Greely, director of Stanford Law School's Center for Law and the Biosciences.
As previously reported by GenomeWeb, Williams is accusing Athena of inaccurately classifying a mutation in the SCN1A gene that the lab detected in her son in 2007. Christian began having seizures at four months old, and in order to determine the cause, one of his doctors ordered the SCN1A test as part of an extensive diagnostic workup that included five muscle biopsy tests, seven genetic tests, ten metabolic tests, and two cell culture tests.
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. According to the Dravet Syndrome Foundation, 80 percent of patients have an SCN1A mutation.
Williams alleges that although Athena correctly detected that Christian had an SCN1A mutation, the lab was negligent in classifying it as a variant of unknown significance (VUS). Two papers — published before Athena issued Christian's June 30, 2007, test report — had identified the same mutation in another patient who had epileptic encephalopathy. Among the authors of one of these papers is Sat Dev Batish, who then was and still is Athena's chief director of genetics.
Moreover, in 2004, Athena licensed a patent (US7,078,515) from Australian firm Bionomics, under which Athena developed and offered SCN1A testing in the US. According to an amended complaint filed by the plaintiffs last week, two of Bionomics' patents, which are continuations of the '515 patent, list the SCN1A mutation (1237T>A) that Christian had as one that "disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype."
Christian's test report includes a glossary in which Athena outlines seven categories that it used to classify any detected variant: known disease-associated mutation, predicted disease-associated mutation, amino acid change of unknown significance, variant of unknown significance, inconclusive, indeterminate, or benign. According to this glossary, "known disease-associated mutations are documented in the literature to be associated with diseases inherited in a dominant manner."
The same glossary noted that VUS "have not been correlated with clinical presentation and/or pathology in the current literature," how these variants affect protein function isn't "readily predictable," and they are similar to disease-associated mutations and benign polymorphisms.
The plaintiff contends that based on its own criteria, Athena should have deemed Christian's mutation to be disease associated, since it was reported in the literature as pathogenic. Since Christian's death, the SCN1A 1237T>A mutation has only been catalogued in the peer-reviewed literature and in publicly accessible variant databases as disease causing based on a single patient.
Based on the glossary in the 2007 report, Jennifer Wagner, a lawyer specializing in legal and policy issues in the genomics field, agrees that accurately classifying Christian's variant depended on the ability of experts at Athena to scan the literature for evidence. But there are and will be lots of cases where the published evidence on a variant will be unclear or conflicting. "This case is a wake-up call, or should be, about the trickiness of this," Wagner, associate director of bioethics research for Geisinger Health System, told GenomeWeb. "[This case] highlights how the industry really does need to become more transparent in how they're making these decisions, [explaining] when they change their minds, why they are changing their minds, and sharing the data."
In addition to accusing Athena of negligence in failing to accurately classify the SCN1A variant, Williams maintains that she never knew about the test — a detail critical to her lawyers' arguments against the defendants' motion to dismiss. Williams said she learned that a SCN1A test had been done on her son for the first time in 2014, and with some difficulty was able to obtain the 2007 report from Athena. Several months later, in 2015, Athena issued Williams an amended report reflecting the reclassification of her son's mutation from a VUS to disease causing.
It is not known precisely when Athena internally determined Christian's variant was disease causing. However, the lab did not provide any new evidence, or rationale, in the 2015 report to justify the change. The plaintiff alleges that this, as well as Athena's initial failure to adhere to its classification criteria and provide timely notification of the reclassification, are violations of federal lab regulations outlined in the Clinical Laboratory Improvement Amendments. Williams is further accusing Athena of knowing it made a mistake in 2007, and of "conspir[ing] to intentionally withhold or cover up the corrected information."
In their motion to dismiss, Quest and Athena stated that the 2015 report doesn't represent information from a "new test" but "simply reports a reclassification of [Christian's] genetic mutation." And any alleged misrepresentation could not have harmed her son, who was already deceased, or Williams, they argued.
These acts are clearly capable of repetition and, as such, have an effect on the public and do concern the public interest.
Quest did not provide comment for this article.
In the latest amended complaint, Williams' lawyers also attempted to strengthen their argument that Quest and Athena's negligent actions are a matter of public interest, because as many as 230,000 children in the US may be eligible for SCN1A testing and others may be harmed. They cite the case of Claire Barnette, who received SCN1A testing from Athena in 2008 and received a VUS result. Claire's testing was discussed as part of a vaccine injury lawsuit that her parents filed several years ago against the US government.
Athena reclassified her variant (2589+3A>T, IVS14+3A>T) as disease causing in 2010. Williams' lawyers highlight in their complaint that Claire's variant was reported in a Dravet patient in a 2007 paper, the same paper that featured Christian's mutation in an epileptic patient (see supplementary table).
Pointing to Claire's 2008 VUS result, the plaintiff's lawyers are accusing Athena of making the same type of mistake they made in Christian's case. "These acts are clearly capable of repetition and, as such, have an effect on the public and do concern the public interest," Williams' lawyers wrote.
Arguing for time
Williams will have to prove that not only did Quest and Athena err in classifying Christian's mutation as a VUS but that he died because of that error. That will be a challenge, but before that Williams' first hurdle is time.
Quest and Athena have asked the court to dismiss Williams' lawsuit because her son died eight years ago, and the genetic test in question was performed nine years ago. In South Carolina, plaintiffs have three years to bring a lawsuit against a licensed healthcare provider from the time they discover they were harmed by medical malpractice, but they lose the right to sue entirely after six years, even if they did not know they were harmed. For ordinary negligence cases there is a three-year limitation but there is also the "discovery rule," which stipulates a three-year deadline from the time the plaintiff realizes there is cause for a lawsuit.
The defendants want the court to deem this a medical malpractice case, while the plaintiff is arguing it is ordinary negligence. "A discovery rule can be crucial in healthcare suits, because medical injuries may be latent and not show up right away, or it may take years for patients to piece together that their symptoms were caused by a healthcare professional's mistake," Barbara Evans, director of the Center for Biotechnology & Law at the University of Houston Law Center, told GenomeWeb.
Williams' lawyers argued last week that they are suing Quest and Athena for common law negligence, so the clock for bringing a claim shouldn't begin running until she received the 2015 report reclassifying the variant as disease causing. "With both the 2007 report and the revised  report in hand, plaintiffs had their first opportunity to recognize defendant's error," Williams' lawyers wrote. "As such, plaintiffs could not have the requisite notice, as suggested by defendants, to trigger the relevant statute of limitations to run until January of 2015."
If there is conflicting evidence as to whether Williams knew or should have known about the test result, then under South Carolina law a jury should decide, her lawyers said. Moreover, in order for this to be a medical malpractice case, Quest and Athena have to be "licensed healthcare providers," but the plaintiffs cite Swanigan v American National Red Cross to argue that the firms don't meet South Carolina's definition.
In that 1993 South Carolina Supreme Court case, Pumpy Swanigan received a blood transfusion collected and processed by the Red Cross during heart surgery, but a year later the Red Cross notified the hospital that the donor was HIV positive. Swanigan tested positive for HIV and died a few years later. His wife sued the Red Cross for negligence, but the Red Cross argued that it was a licensed healthcare provider and the plaintiff was making medical malpractice claims that were barred by the three-year statute of limitations. The court held that the Red Cross was not a healthcare provider, "because it plays no role in the care of patients" and merely employing healthcare professionals wasn't enough.
Quest and Athena's claim to be a licensed healthcare provider "is a very big stretch," Geisinger's Wagner said. Still, in its motion to dismiss, the defendants interpret Swanigan as supporting their claim to be a healthcare provider and even quote the definition of "health care" from Webster's College Dictionary as "any field or enterprise concerned with supplying services, equipment, information, etc., for the maintenance or restoration of health."
It's hard to predict how a judge will decide the motion to dismiss, according to legal experts who spoke to GenomeWeb. Clinical laboratory tort law is an unclear realm, because cases seldom reach the courtroom. "It's surprising to see how few cases against clinical laboratories have ever been litigated to conclusion," said Evans, who has had scholarly interactions with parties in Williams v Quest/Athena, but is not directly involved in the case. "This is one reason why the legal rules for labs seem eternally murky."
A fully litigated outcome might give us some much-needed clarity on key legal questions that genomic testing laboratories are facing today.
Evans cited work by Marc Galanter from the University of Wisconsin Law School in 2004, who found that less than 2 percent of civil cases — in other words, less than 1 in 50 tort suits and other non-criminal cases — are decided by trials in federal courts. "The public thinks of a tort lawsuit as a big courtroom drama, like the ones on TV shows, but it really is very rare for a tort case actually to go to trial," Evans reflected.
Many lawsuits don't survive pretrial motions, such as a motion to dismiss, and the overwhelming majority are settled out of court. There is pressure to settle on both sides, Evans explained. Labs prefer to settle than risk setting "an undelectable precedent," and plaintiffs often settle because suing a lab is expensive. Proving, for example, that a lab's error caused an injury requires teams of genetics and medical experts to navigate complex scientific issues. But the impact of these out-of-court settlements, Evans explained, is that they "don’t leave a trail of published case law to clarify what a lab’s legal duties are and how the regulations actually work."
While Evans cannot predict whether Williams' lawsuit will survive Quest and Athena's motion to dismiss and ultimately go to trial, as a law professor, she wishes to see the case litigated and decided. "[This would] not only give the plaintiff her day in court but also ... a fully litigated outcome might give us some much-needed clarity on key legal questions that genomic testing laboratories are facing today," she said.
Williams' lawsuit cites a number of CLIA violations against Quest and Athena in an attempt to make the case that an error occurred because it didn't have appropriate classification and reporting systems in place. The US Food and Drug Administration wants to regulate lab tests precisely because the agency believes CLIA regulations are insufficient to protect the public's health. And as the market for genetic tests expands rapidly, some industry players are even starting to acknowledge that variant interpretation is a critical challenge that labs need to work together to resolve.
Other industry observers, meanwhile, have worried that this case could have a chilling effect on a still nascent field. Will this case, if successful, increase liability for labs? Every time a lab reclassifies a variant, will it be considered an error?
"I've seen some of the comments that a plaintiff’s victory in this [case] would be terrible and kill genetic testing. That's bullshit," Greely said. "Mistakes happen. People pay for their mistakes." Because this is the reality within the US legal system, whether the error is made by an individual, a grocery store, or a hospital, "there's no reason to think that genetic testing labs will dry up and blow away because they are held responsible for mistakes," he added.
Variant classification, by its very nature, is painstaking, repetitive work. Classification scientists have to keep up with the literature and the latest techniques for determining the biological function of genetic variants. They must review their determinations constantly.
"There is no true truth for most variants. Most interpretations are expert opinions based on an evaluation of evidence," said Heidi Rehm, director of the Laboratory for Molecular Medicine at Partners HealthCare Personalized Medicine, in a recent Nature Methods editorial. Rehm has been encouraging labs to improve variant classifications by submitting them to public repositories, such as ClinVar, and working with other researchers and labs to resolve discrepancies.
"Simply amending a VUS call to benign or disease causing can't be actionable in and of itself," Greely said. "That's the sort of thing we want labs to do."
But Williams isn't alleging that Athena made an error simply because the lab sent a report last year in which her son's mutation was reclassified from a VUS to disease causing. She is alleging that Athena failed to correctly classify the mutation from the get go, in 2007, based on the evidence available at the time.
Given the same evidence, could a lab be reasonably expected to classify the mutation as disease causing instead of a VUS? "That's the kind of question we ask all the time, [and] … those are hard questions," Greely said. "But there is no reason to think that courts will think that calling something a VUS is always negligent. Most of the time it won't be, but sometimes it will be. Whether it was here is the core question in this case."