5 November 2014
In 2006 PHG Foundation published its report evaluating the use of microarray comparative genomic hybridisation (array CGH) in the diagnosis of learning disability. In the report we recommended that not only should array CGH be used in the second-line test setting (following a negative karyotype) in which it was evaluated, but that further work should be undertaken to compare how array CGH would work in a first-line test setting (i.e. that array CGH should be the initial investigation rather than karyotyping). This report, along with its sister publication, Parents as Partners , was extremely well received by the clinical genetics community within the UK.
We presented our follow up work on the evidence for using array CGH in a first-line test setting at a meeting hosted by the UKGTN, where it was agreed that there was compelling evidence for the benefits of implementing array CGH as a first-line test (i.e. to replace karyotyping as the initial investigation). This led to the Association for Clinical Cytogenetics producing an Array Best Practice Guideline in December 2011 which stated that “Microarray testing may be used as a ‘first line test’ replacing conventional karyotyping”.
But despite a compelling evidence-base, and both guidance and recommendations from the Association for Clinical Cytogenetics and the UKGTN reiterating this position, a UK-wide survey of the regional genetics services in 2012 estimated that of all the patients referred for unexplained learning disability and developmental delay, only 68% received an array CGH. Furthermore, the survey did not differentiate between use of the test in a first-line or second-line setting. Delays in implementation have generally been blamed on the lingering but, as we demonstrate below, outdated, perception of ‘high cost’ surrounding the routine use of array CGH as a first-line test by commissioners and managers. This in turn has led to inefficient use of limited laboratory resources by allowing array CGH to remain a second-line test for longer than necessary.
Today, karyotyping is clearly no longer the gold-standard within this setting and it is well acknowledged that array CGH is a superior test for diagnosing chromosomal abnormalities at a far greater resolution. And the evidence not only supports the clinical effectiveness of array CGH. An economic evaluation published in 2007 – and referenced in our original report - suggested that the use of array CGH would be cost-effective regardless of the diagnostic outcome (i.e. either positive diagnosis or negative result) and that its use should be seriously considered in routine clinical practice.
Our latest work in this area, looking at cost-effectiveness of using array CGH in a first-line setting versus a second-line setting, shows the first-line setting as dominant - array CGH is both more effective and cheaper as a first-line test. We have estimated a cost-per-diagnosis of first-line testing to be £2,544.42 versus £4,819.44 for second-line testing. This work shows that significant efficiency savings that can be made within clinical genetics services before we even start to consider the benefit to patients and their families of making both more and earlier diagnoses. It is possible that actually quantifying that benefit may help such advances move more readily into NHS clinical pathways in a timely manner. You can read more about this work and its results in the short report Array CG H testing for learning disability - when is it worth it?