Steve Abbs is working as a genetics consultant with CliniSys | MIPS. In the first of a series of blogs on the developing field of genomic testing and precision medicine, he argues how the genetics laboratory hubs being set up in England can benefit from deploying a modern LIS to enable them to run more efficiently, deliver results effectively to clinicians, and lay the IT foundations for precision medicine.
We have reached an interesting point in the development of genetic medicine in the UK. It is no longer the preserve of a few, small research groups. It is on the cusp of becoming a routine part of medical practice, and an established diagnostic tool for some cohorts of patients.
To support these developments, genomics labs will need to change and the technology they use will need to change with them. They will need to move away from the paper-based management of samples, adopt standardised processes, and deliver results to clinicians in a meaningful way that can be integrated seamlessly with the electronic patient record. In short, it is time for genetics labs to adopt a modern laboratory information system; a genetics LIS.
Moving from lab to hub requires a LIS
How have we got to this point? Genetics was originally two disciplines. Cytogenetics looks at genetic material under a microscope in order to identify chromosomal abnormalities. While molecular genetics looks at changes at a more detailed level of the DNA sequence within genes and the genome.
As a discipline, cytogenetics made big advances in the 1960s and 1970s, while molecular genetics came along in the 1980s. The first human gene to be sequenced was the gene for cystic fibrosis, in 1989. Since then, 20,000 genes have been sequenced, while the first whole genome, for Haemophilus influenza, was sequenced in 1995, and the first human genome followed in 2003.
So, there has been rapid and impressive progress in this area. On the lab front, the developments encouraged the NHS to set up labs to provide clinical genetic services. Most of them came out of a research setting and initially were very small. But to build on the 100,000 Genomes Project that ran from 2014-18, the NHS in England decided to establish a national Genetic Medicine Service.
This is being delivered by seven genetic laboratory hubs or GLHs that were chosen through a national procurement process. The GLHs are delivering the National Genetic Test Directory, which is in two parts, covering rare or inherited diseases, and cancers.
Historically, genetic and cancer tests have generally been provided in different laboratories, as molecular and cytogenetic tests have been. In theory, the GLHs are uniting the two disciplines of cyto and molecular genetics and testing for both cancer and inherited disorders.
However, in practice, we know that the degree of integration is variable, and any process that involves changing traditional practice is lengthy and difficult. This is one area where the deployment of a modern LIS can help; as pathology networks have proved, using a common IT system encourages common working practices [a subject I’ve blogged about in more detail here].
Replacing risky, costly paper processes
One of the principal reasons for setting up genetic laboratory hubs is that it would be impossible for any one lab to deliver all the tests in the National Genetic Test Directory. All seven GLHs will provide the more commonly requested or core tests, while samples will be sent from one lab to another for specialist, rarer tests, or to a national central laboratory for whole genome sequencing.
Sending samples around the system requires a considerable amount of administration and, at the moment, this is a very paper-based process. Many orders come into a lab on paper, they are sent on to other labs with accompanying paperwork, and if they are sent to the central lab for whole genome sequencing they have to be transcribed onto the new national genetics informatics system.
This is where a modern LIMS would really come into its own, because the whole purpose of a LIMS is to keep track of orders, samples and results. Similarly, when genetics labs are running tests there is a lot of paper involved. Without a functioning LIS, there is reliance on Excel spreadsheets to keep on top of the workload, which means there is a lot of transcription and manual manipulation of data.
Integrating the analysers with a LIS would make genetics labs safer because there would be less potential for human error, and more efficient because there would be a massive reduction in the amount of time spent keying and checking data. It would also mean the labs were ready for scaling up to the next generation of analysers, which are coming.
Supporting the interpretation of complex data
These arguments in favour of a LIMS will be familiar to pathologists – who would probably find it hard to imagine running a modern path lab without one! But a genetics LIS needs some specific features.
One is that it needs to be able to report results to clinicians in a way that is useful. The output from a genetic test is rarely a simple number. There tends to be a qualitative element that explains how the result was arrived at and what it is likely to mean for the clinician, their patient and their family.
That’s because for most of the inherited conditions that you might be running a test for there is no treatment available, currently. Instead, the test is initially a diagnostic test for the index case, and after that the results are available to be used in a predictive manner. For example, they may be used to advise a family on their chances of having another severely ill child, or to let relatives know that they are at greater risk of developing a condition later in life, like Huntington Disease.
A genomics LIMS will bring all that complex information together. The genetics LIS that CliniSys | MIPS has introduced to the UK market, GLIMS Genetics, facilitates this through its integrated pedigree drawing tool. This enables the family tree to be drawn, using data on relatives that is stored in the database. Laboratory results can then readily be displayed on the pedigree drawing, providing a visualisation of how genetic variants are tracking within a family.
A genetics LIMS will also give direct access to expert interpretive resources; GLIMS Genetics can integrate with leading databases (ClinVar, dbSNP, HGMD and others) and, importantly, it includes a function for reviewing the ACMG classification of variants that have previously been reported from the LIS and that may need re-reviewing in light of new evidence that has meant a re-classification.
Integrating LIS and EPR lays the foundation for precision medicine
What is the future for genetic medicine? One positive development is that therapeutic interventions for severe inherited conditions are starting to become available. However, they are often very specific to a very specific pathogenic variant.
This means that, if a patient is going to benefit, the causative variant needs to be recorded accurately in their medical history to enable clinicians to readily identify whether a patient is suitable for treatment, or could be added to a patient registry used to source patients who are eligible for clinical trials.
Another positive development is that whole genome sequencing is becoming more common. Although the primary indication for receiving whole genome sequencing is likely to be a diagnostic test, the fact that the genetic sequence data is available means it can be interrogated to guide clinical management.
One important reason for doing this interrogation is to identify genetic variants associated with pharmacogenomic implications. A nice example is the application of four sequence variants in the DPYD gene that control how drugs are broken down in the liver.
These can affect the risk of a patient experiencing a severe or fatal side effect from the fluoropyrimidines that are commonly used to treat a number of cancers. The genotypes at these four loci are used to indicate the starting dose for treatment with fluoropyrimidines, or whether patients are given a completely different treatment, in order to minimise the risk of an adverse effect.
Adverse reactions to drugs are a huge and expensive problem in the NHS, as in all healthcare systems, so being able to avoid them like this is a major benefit for patients and for healthcare funding bodies. But to do that, the genetic data needs to be readily available to the clinician treating the patient.
These examples of precision medicine mean that a final – and very important – justification for genetic laboratories to deploy a modern LIS is to enable full integration with hospital electronic patient record systems so that the benefits of personalised medicine can be fully realised.
Making the right IT investments, now
These kinds of scenario are only going to become more common as more personalised therapies become available, as more clinical trials take place, and as whole genome sequencing becomes cheaper and more embedded in routine healthcare. Already, genetic data is being pulled into clinical multi-disciplinary team meetings, to help clinical teams decide how best to manage a patient.
Having direct connectivity to all the relevant information from the genetic LIS via the EPR would greatly facilitate these meetings. But in the future, it may be possible for clinicians to enter a patient’s symptoms into a rules-engine within an EPR, pull up a standard genetics order set, and send off for the tests they need to get an answer.
There is no doubt that precision medicine is sending ripples of excitement through the clinical community and that it holds out enormous potential for delivering more accurate treatment and prevention strategies to patients. However, it can only happen if we have good integration between the systems that are used to order tests, to run genetics labs, to interpret and report results, and to record patients’ histories.
GLIMS Genetics is designed for clinical genetics laboratories and can help labs improve their efficiency, catalyse transformation and standardisation across genomic networks, handle and communicate complex genetic data, and integrate with numerous local, national, and international informatic systems and resources to support patient management and precision medicine.
GLIMS Genetics is a comprehensive, modern LIS for state of the art genetics laboratories, and can help transform genetic medicine in the NHS.