Accountability of clinical laboratories

Patients and medical practitioners often “trust the system” when it comes to clinical laboratory testing and test reports to make diagnoses and decide on further medical treatment. But when laboratory tests involves a rapid developing field such as genomics, test results, and more specifically the classification thereof, risk being outdated by the time treatment decisions are made due to new research findings. If the medical practitioner then prescribes ineffective or fatal treatment to a patient based on the laboratory’s report, who will be accountable for harm suffered as a result thereof?

Williams v Quest Diagnostics

A case in point is the matter of Williams v Quest Diagnostics, Inc. et al. which is currently pending in the federal court of Columbia (USA), and although the court has not yet decided on the issue of accountability, the legal questions raised by this matter should serve as a serious wake up call to all clinical laboratories, especially involved in genomics for clinical purposes.

In this matter Williams’s son, Christian, began having seizures when he was only 4 months old. Doctors ineffectively treated his seizures with sodium channel blocking medication and subsequently suspected that Christian may have Dravet syndrome, also known as Severe Myoclonic Epilepsy of Infancy (SMEI). At the time Christian suffered from these seizures SCN1A was known to be one of the most important genes involved in epilepsy. Mutations in this gene caused a spectrum of epilepsy phenotypes of which the most severe was Dravet syndrome. Of importance was the fact sodium channel blocking medications are to be avoided in patients with a mutation of this gene as this treatment could exacerbate the seizures.

Athena laboratory (which is a subsidiary of ADI Holdings which is itself a subsidiary of Quest Diagnostics) issued a report 6 months after genetic testing was ordered. This report clearly indicated that Christian had a SCN1A mutation and classified the mutation as a “variant of unknown significance”, with other words not specifically known to be pathogenic or benign. This report further failed to indicate any specific treatment or any treatments that had to be avoided.

Tragically doctors continued to treat Christian for an unspecified mitochondrial disorder with increasing doses of sodium channel blocking medications – standard for epileptic seizures, but contraindicated for patients suffering from Dravet syndrome – and Christian died, aged 2 years.

Revised laboratory report

Eight years after issuing their initial laboratory report, Athena and Quest Diagnostics jointly issued a “revised report” that listed Christian’s SCN1A gene variant as a “known disease-associated mutation” and specifically directed the recipient of the report to “disregard the previous report”. The revised report did not list any new references or information to support a reclassification of this gene variant from the previously “unknown” to the current “known” classification, nor did it identify the date on which the new classification occurred or who directed such a decision. There was further no indication of any attempt by Athena or Quest Diagnostics to notify either the treating doctor who has ordered the original test or the patient affected by the new classification.

In the pending matter between Williams, Christian’s mother, and Quest Diagnostics, Williams argues that the latter report seems to be an attempt to correct an error in the original classification, rather than to serve as an update or reinterpretation resulting from recent scientific developments and understanding since the issuing of the original report, and further alleges that Quest Diagnostics:

  1. failed to provide genetic confirmation that Christian had Dravet syndrome;
  2. failed to adhere to their own post analytical classification system;
  3. failed to notify anyone of the reclassification of the variant the lab had identified;
  4. failed to identify the contraindicated treatments (sodium channel blocking medications).

Legal considerations

Although this matter is still sub judicae, it raises interesting and important legal questions:

  1. To what extent can a laboratory be held accountable to adhere to their own variant classification system, and when a mistake is made, that they identify and correct it?
  2. May ordering medical practitioners blindly rely on reports issued by laboratories conducting genetic testing, or do they have an individual professional obligation to also be competent in genomics?
  3. Whose responsibility is it to stay up to date on the latest scientific developments and literature to ensure accurate interpretation in laboratory reports of genetic test results, including making medical treatment decisions on the basis of these reports?
  4. Whose responsibility is it to revisit medical decisions based on test results that may have become outdated in the meantime?

Medical negligence

Delictually speaking a laboratory (or a medical practitioner) can only be held liable for damages resulting from its negligent acts or omissions. The matter of     Kruger v Coetzee 1966 (2) SA 428 (A) provides the classic test for determining negligence as follows:

  • (a) a diligens paterfamilias in the position of the defendant –
    • (i) would foresee the reasonable possibility of his conduct injuring    another in his person or property and causing him patrimonial loss; and
    • (ii) would take reasonable steps to guard against such occurrence; and
  • (b) the defendant failed to take such steps.”

Considering the conduct of Athena Laboratory in Christian’s case, it is obvious to foresee that the ordering medical practitioner would strongly rely on their report and is it thus reasonably foreseeable that an incorrect classification of Christian’s genetic mutation will have serious implications on the patient’s health, resulting from the medical practitioner’s treatment recommendation based on the incorrect classification. Athena Laboratory should further have foreseen the “reasonable possibility of (their) conduct injuring another” by failing to notify any of the involved parties of their reclassification of the specific gene mutation due to the fact that the ordering medical practitioner may have changed his medical treatment prescription in view thereof, which will have direct and serious impact on the patient .This, however, begs the question to what extent an ordering medical practitioner must take responsibility for the correct interpretation of genetic test results and whether a medical practitioner must have a reasonable understanding of genomics to enable him or her to critically evaluate laboratory reports before prescribing medical treatment. Considering that genomics is a fast developing and highly specialised biotechnology field, it seems unreasonable to expect that, as in Christian’s case, a paediatrician must keep up to date with the latest genomic developments to be able to question laboratory report results. With such a tsunami of research papers in genomics it seems almost unreasonable (and impossible) to expect laboratories to keep abreast of the latest developments for classification purposes. In this regard it should be noted that although Athena apparently correctly identified Christian’s gene variant, they review the scientific literature incorrectly, as there were already two publications that associated this specific mutation with Dravet syndrome (Berkovich et al, 2006 and Harkin et al, 2007) and should Christian’s variant have been classified as a “known disease associated mutation.” It is also noteworthy that one of Athena’s own directors, Dr Sat Dev Batish was a co-author of the Harkin et al paper which was published prior to the issuance of Christian’s above report.

The Consumer Protection Act

Although the Consumer Protection Act 68 of 2008 does not apply retrospectively, it has changed liability in respect of the above dramatically since its enactment on 1 April 2011. Section 54(1)(b) specifically stipulates that consumers, which includes patients making use of laboratory test services, are entitled to the performance of services in a manner and of a quality that persons are generally entitled to expect. Should these services fall short of consumers’ expectation and causes them harm, section 61 introduces a no-fault liability regime which determines that the provider of such services will be held liable “irrespective of whether the harm is the result of negligence on the part of any of these parties.” Not only does a patient no longer needs to prove negligence on the side of the laboratory, but the Consumer Protection Act further stipulates that the whole chain of supply, thus including the ordering medical practitioner will be held liable when harm is suffered.

Under these circumstances it is advisable that patients obtain a copy of their laboratory test result and seek a second or updated opinion; that medical practitioners seek training in genomics, although it is questionable whether even ongoing training in this regard will provide meaningful competence; and that laboratories keep literature scans up to date and strictly adhere to their internal classification schemes and importantly, immediately notify ordering medical practitioners and patients of any reclassifications relating to previous reports done or at least attend to mass notifications on a public-facing website, which would be preferable to mere silence.

By Marietjie Botes