We are all familiar with the long lists of rare potential side effects our medications have,
but are usually none the wiser as to whether we will be that unlucky ‘1 in 1,000’ who experiences them.

On top of these potential side effects, it turns out that most prescription medications – including commonly prescribed medications such as painkillers and antidepressants – are only effective for 30% to 50% of people. A significant part of this is down to our genetics.

Sitting at the intersection of genomic medicine and pharmacology, pharmacogenomics (PGx) enables providers to tailor prescriptions to the unique variation in an individual’s genome. Certain genomic variations determine how a patient will react to certain drugs – they may be genetically predisposed to a severe reaction to one medication or completely unresponsive to another.

By the time we’re 70, 90% of us have been exposed to at least one drug with PGx guidance that could have predicted how we would react. Routine use of tools that can provide an understanding of what a patient’s body will do to a drug – and what the drug will do to the patient’s body – before they take it could be revolutionary.

Predicting reactions

Adverse reactions or total lack of response to medications are remarkably common. Around 8% of the UK population lack the gene that enables codeine to work properly, meaning that they get no pain relief whatsoever from a medication that others use only when in severe pain. Another variation affecting 1 in 500 people predisposes them to hearing loss if they take gentamicin, an intravenously administered antibiotic used to treat serious infections. While these affected groups are individually small, almost 99% of people carry at least one genetic variation that will affect the way their body responds to certain drugs.

Some people may never encounter the drugs they would have an abnormal reaction to, but eliminating that risk remains invaluable. Approximately 6.5% of hospital admissions in the UK are caused by adverse drug reactions that could well have been predicted. If PGx testing was implemented across the population, this could have phenomenal impacts on the NHS and public health.

Personalised prescribing

Knowing how someone’s body will react to medication helps avoid adverse effects, optimise dosage, and ultimately provide the most effective treatment for each patient. If information about these genetic predispositions were to be combined with patient health records, clinicians would be able to create perfectly tailored treatment plans that would yield optimal results.

Using genomics to help tailor treatments is something that the NHS is progressively embracing across the UK. The GenOCEANIC project that is currently being undertaken by the Belfast Hospital and Social Care Trust is powering personalised care and earlier diagnosis in Northern Ireland. Created in collaboration with Cambio, the platform combines the information held within genome sequences with patients’ electronic health records, building a full picture of their health to help reduce time to diagnosis and improve overall outcomes.

GenOCEANIC also powers whole-genome sequencing, which is playing an increasing role in speeding up rare disease diagnoses. The results of a whole-genome sequence can help match patients to appropriate treatment pathways by identifying medications and interventions that will be the most effective as well as reducing the likelihood of an adverse drug reaction.

Challenges facing PGx

As with all new technologies, introducing the regular use of PGx testing in the NHS will face some challenges. Increasing healthcare providers’ knowledge and confidence around the subject will be integral, as will improving public understanding of what these tests can – and can’t – predict.

Another vital component will be funding. Public finances are stretched thin in the wake of the pandemic, so the NHS will likely have to have an initial focus on gene-drug pairs that are likely to be the most clinically and cost-effective. Pairings that have the most severe reactions and are the most commonly occurring will likely be prioritised over rare and mild reactions. Creating an equitable service that benefits the entire population will be a challenge, and it is important that those who are susceptible to rare adverse reactions are not left behind when planning the implementation of PGx testing. The deafness caused by a reaction to gentamicin, for example, is relatively uncommon but has a large impact on the patient’s life.

The full strategy for implementing pharmacogenomics across the NHS is laid out in the personalised prescribing report and encompasses challenges of funding, prescriber knowledge and education, patient engagement, decision support tools – such as Cambio’s CDS – and clinical governance.

One major point that the report stresses is future-proofing any systems that are put in place so that PGx-based recommendations can be added and amended as the research base grows. Systems such as GenOCEANIC have been built with these ongoing changes in mind, helping the NHS remain adequately prepared for future developments without repeatedly spending time and money on introducing new systems.