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Genetic testing in the acute setting: a round table discussion
  1. William G. Newman
  1. Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK
  1. Correspondence to Professor William G. Newman, Manchester Centre for Genomic Medicine, University of Manchester, Manchester M13 9WL, UK; william.newman{at}manchester.ac.uk

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As a clinical geneticist I have been amazed at the speed of discovery over the past 20 years. The specific genetic causes of thousands of rare genetic conditions have been defined due to improvements in genomic sequencing, computing power and international collaborations to phenotype individuals with similar clinical features. This knowledge has resulted in an increased ability to make accurate molecular diagnoses which informs optimal treatment and clinical care, can remove the need for unnecessary investigations and informs reproductive decision-making. However for any given individual, this genetic testing can often take weeks or months before the initial genetic diagnosis is made within a family. Occasionally genetic information is required more quickly to define a clinical action.

For years point of care testing (POCT) has been a mainstay of clinical care, for example, in confirming pregnancy or monitoring blood glucose. I had been keen to explore scenarios where a genetic POCT could be employed in clinical practice. To me, an obvious example appeared to be neonatal testing to avoid gentamicin-induced hearing loss. Here was a situation where we had known about the genetic predisposition to profound, irreversible hearing loss for 25 years and not had the means to intervene.1 A POCT which could generate a result at the bedside and facilitate antibiotic administration within an hour in a baby with suspected sepsis could, in theory, result in the prevention of nearly 200 babies each year in the UK, and potentially many more across the world, from going deaf.

We considered many issues in the design of the PALOH study including use of a non-invasive cheek swab to ensure that a sample could be tested rapidly. We considered whether the introduction of this test would be a quality improvement study rather than that requiring ethical approval. We were informed the latter, as the result of the test would lead to a change in routine clinical practice. The assay required CE marking before the study could commence to ensure its analytical validity. We discussed the project widely at meetings, with colleagues and co-investigators and with our stakeholder group, comprising patient/parent representatives, charities, experts in commissioning, implementation medicine and the National Health Service and considered three main potential consent scenarios. First, should we obtain prospective consent (ie, before the test was conducted), second could we obtain retrospective consent (after the baby has been tested) or alternatively use an opt-out consent model. As the first scenario is impractical in the acute setting, where a result is required as quickly as possible (and a mother may have just had an anaesthetic related to delivery) and the second had many practical barriers, we opted for an opt-out consent. This opt-out consent essentially was asking the parents of the tested newborn for permission to use anonymised information about the test—did it happen in time, did it work, what was the result—in the reporting of the study. Many studies in the acute setting (in the emergency room) or indeed in neonates have favoured an opt-out model. Where our study differed from previous studies was that we intended to undertake a genetic test. The application was approved by the ethics committee. However, I had not previously considered that we had potentially fallen foul of the Human Tissue Act, 2004,2 and that as the chief investigator of the study, this potential breach could lead to a 3 year prison sentence. In theory I was taking a DNA sample without prior consent and undertaking a genetic test. To me this seemed counter-intuitive to the spirit of the Act. I was trying to effect an entirely preventable cause of severe morbidity. What could be the downside of that? On reflection, it was important for me to consider that safeguards are in place. I am not proposing to undertake any random genetic test or a full genome sequence without prior consent, but a very specific assay that has a very clear binary outcome—presence of the variant means avoiding the antibiotic and using an alternative, absence of the antibiotic and the standard antibiotic can be used. In many healthcare scenarios professionals undertake tests and examinations of patients without prior explicit consent. To my mind, here was another example of that. This test was being done as part of the unwritten bond of trust between healthcare provider and patient that any test would only be done where a clear benefit for the individual could be articulated.

Fortunately, the Act had the flexibility to allow us to proceed with the study as we were able to argue that this is essentially a diagnostic test and only hasn’t previously been implemented because the technology was not available. I do not believe that the interpretation provides me with carte blanche to undertake other genetic testing on the sample taken from the baby. It does not allow me to use this POCT in other healthcare settings where I haven’t explained to my patient why I might want to use it. It is a very narrow application of the test that myself and my co-investigators will respect to ensure that we can generate the data that will hopefully mean that this test can be adopted into routine clinical care and set a precedent for the appropriate use of acute genetic tests in situations where obtaining prior consent is not possible.

References

Footnotes

  • Twitter @geneticbill

  • Funding This study was funded by National Institute for Health Research (NIHR).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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