Saving Money and Lives

Pharmacogenomic testing could save the NHS money in the long term, reduce the risks of side effects, and deal with the problem that drugs do not work for many patients. Pharmacogenomics^[1] is the understanding of how genes impact an individual’s response to medications and how they respond differently to drug therapy based upon their genetic makeup or genes. Pharmacogenomics uses information about a person’s genetic makeup, or genome, to choose the drugs and drug doses that are likely to work best for that particular person. This new field combines the science of how drugs work, called pharmacology, with the science of the human genome, called genomics.

Genetic differences mean that a medicine can be safe for one person but harmful or ineffective for another. One person may experience severe side effects from it. Another may not – even when given a similar dose.

Personalised medicine is based on using an individual’s genetic profile so that the doctor can make the best therapeutic choice by facilitating predictions about whether that person will benefit from a particular medicine or suffer serious side effects.

Drugs are generally tested on a large population of people, and it is the average response that is reported. This sort of evidence-based medicine (that is, medical decision making based on empirical data) relies on the law of averages, whereas personalised medicine recognises that no two patients are alike.^[2]

Picture Credit/Attribution: “IRRI Genetic Transformation Laboratory – GN7_2020-6” by IRRI Images is marked with CC BY-NC-SA 2.0.

Significant progress has been made in using genomics to determine the safest, most effective course of treatments for individuals and, as these programs scale and go mainstream, healthcare has reached a tipping point where it is starting to deliver on its promise of improving the health of communities and significantly lowering healthcare costs. 

ThermoFisher Scientific reports that as recently as 2016, the estimated annual cost of drug-related morbidity and mortality in the US resulting from non-optimised medication therapy was nearly $530 billion – equivalent to 16 per cent of the total US health care cost. That’s a mighty big pile of dollars. The Telegraph on 29^th March 2022 suggests the UK cost has been estimated at £2 billion a year, which appears to be wrong.

The US Centers for Disease Control and Prevention (CDC) says:

“Pharmacogenomics is an important example of what is called ‘precision medicine’, which aims to tailor medical treatment to each person or to a group of people. Pharmacogenomics looks at how a person’s DNA affects how they respond to drugs. In some cases, your DNA can affect whether you have a bad reaction to a drug or whether a drug helps you or has no effect. Pharmacogenomics can improve your health by helping you know at the outset whether a drug is likely to benefit you and be safe for you to take. Knowing this information can help your doctor find medicine that will work best for you.”^[3]

How pharmacogenomics differs from genetic testing^[4]
Standard genetic testing is a type of testing that searches for specific genes. For example, a test may look for BRCA1 and BRCA2 genes, which are linked with a higher risk of breast and ovarian cancer. The results from a standard genetic test may prompt preventive or risk-reduction steps. These include:

• More frequent cancer screening
• Lifestyle changes
• Preventive treatment

It is important to note that even though a genetic test may confirm a diagnosis, there may be no intervention or treatment available.

Pharmacogenomics is a type of genetic testing. It looks for small variations within genes. These variations may affect whether genes activate or deactivate specific drugs. Test results help the doctor choose the safest and most effective drug and dose. Pharmacogenomics is constantly changing. Researchers continue to identify gene variations that affect how a drug works. As personalised medicine grows, testing for gene variations may become more common.

Same Treatment, but Different Results
The Telegraph article on 29^th March 2022 gives three examples:

• Pain Relief: about 8% of the British population lack the gene that allows Codeine to work properly – meaning they will not get any pain relief taking that drug.
• Blood Thinners: some people taking Clopidogrel lack the enzyme needed to convert its active substance – meaning they are therefore at a higher risk of stroke.
• Antibiotics: about one person in 500 has a gene variant that predisposes them to hearing loss with the antibiotic Gentamicin.

The British Pharmaceutical Society and the Royal College of Physicians are calling for a more personalised treatment in future with genetic testing so that drugs are not prescribed if they would do more harm than good. Prof Sir Munir Pirmohamed, chairman of the working party looking into the problems, said: “…90% of drugs work in only 30% to 50% of people. About 6.5% of admissions to adult hospitals are caused by adverse drug reactions.” He added: “By the time people reach age 70, there is a 70% chance that they would be taking at least one drug that has variable responses. In the 21^st century, we need to move away from the paradigm of ‘one drug and one dose fits all’ to a more personalised approach.”

The report by Professor Sir Munir Pirmohamed’s working party^[5] noted that:

• The UK spends approximately £16.8 billion per year on prescription drugs, and this will soon rise to £20 billion, but currently, only 50-75% of those drugs prescribed to patients are effective.^[6]
• Ineffective use of drugs, and patients suffering adverse drug reactions (ADRs), place a huge burden on the NHS (and other healthcare systems worldwide) in terms of consumable costs and clinical contact time. ADRs alone account for 6.5% of hospital admissions and 14.7% of extended hospital stays^[7], equating to 8,000 hospital beds being occupied at any one time, at the cost of £2 billion per year.
• Incorporating pharmacogenomics (the study and clinical application of the genomic determinants of drug response) into the prescribing process has the potential to deliver safer, more effective treatments at optimal cost, to support the NHS develop the Medicines Value Programme.^[8]
• Explaining pharmacogenomics test results to patients may present new challenges, and currently, many clinicians will not have the time, knowledge, or confidence to discuss such results with their patients. An accompanying national strategy to improve genomic literacy amongst healthcare professionals will underpin confidence in testing and relieve concerns regarding the consent process. Slow implementation, dealing with single variants initially will give clinicians time to develop their knowledge and counselling skills. The implementation of pharmacogenomics into any healthcare system does not need to be dependent on a single sector, for example, medical professionals, but should be developed around multi-disciplinary teams, including pharmacists and nurses. This would enable the process of when to order tests, how to interpret results and when to take a prescribing decision to become seamlessly integrated into current clinical pathways as a normal part of the care of a patient, in the same way as biochemical testing is currently carried out.^[9]

With the increasing interest in genomics and the increasing availability of rapid and cost-effective genotyping technologies, the introduction of pharmacogenomics for a healthcare system such as the UK NHS, could be seen as the exemplar for worldwide implementation.

Genetic Tests: Experts urge caution over home testing^[10]
In 17^th October 2019, the BBC reported that experts warned people not to make health decisions based on genetic tests they do at home. A University of Southampton team, writing in the British Medical Journal, warn results can be unreliable, and the tests could be wrongly reassuring – or lead to unnecessary worry.

23andMe, one of the companies offering tests, said there were “many cases” where results had prompted further checks and preventative treatment. Prof Anneke Lucassen, president of the British Society for Genetic Medicine and a consultant in clinical genetics at University Hospital Southampton, led the research.

The research does not cover genetic screening offered by the NHS to people with a family history of a disease or other risk factors. Instead, it covers so-called direct-to-consumer (DTC) genetic tests.

Prof Helen Stokes-Lampard, who chairs the Royal College of GPs, said: “Genetic testing shouldn’t simply be done to satisfy a patient’s curiosity about their health, as the results could have very real implications. Our members (GPs) have reported patients coming to see them with the results of commercial genetic tests, asking for them to be interpreted – and some commercial companies actually advise this instead of providing the necessary advice and feedback themselves. This is not a good use of our time or NHS resources and should be the direct responsibility of the companies being paid to perform the tests.”

Current Practice of Protection in Genetics
The development of genetic testing has raised numerous concerns about autonomy, confidentiality, privacy, and equity that are exacerbated by the range of contexts in which such tests are undertaken, the sheer volume of tests that could be offered, the many uses that can be made of test results, and the variety of institutions that store genetic information, says the National Center for Biotechnology Information, US National Library of Medicine. To date, most genetic testing has been done in the reproductive context or with newborns, to identify serious disorders that currently or soon will affect the foetus or infant. However, the types of genetic conditions or predispositions that can potentially be tested for are much broader than those signalling serious, imminent diseases.

You can read the full article at: https://www.ncbi.nlm.nih.gov/books/NBK236044/

“Experts say to predict how individuals will respond to common medicines, genetic testing should be implemented without delay to reduce the risk of side effects and ensure that everyone is given the right drug at the right dose. About 6.5% of UK hospital admissions are caused by adverse drug reactions, while most prescription medicines only work on 30% to 50% of people. A significant part of this is due to genetics: almost 99% of people carry at least one genetic variation that affects their response to certain drugs, including commonly prescribed painkillers, heart disease drugs and antidepressants.“

Source: https://www.theguardian.com/science/2022/mar/29/experts-push-for-genetic-testing-to-personalise-drug-prescriptions

The Pros and Cons of Genetic Testing^[11]
Although genetic testing has increased in popularity, it is not for everyone. The results of genetic testing can often be uninformative and ultimately can cause more stress and anxiety over the possibility of a disease you may never get. Only when there is an effective solution available to prevent or treat the condition tested for should genetic testing be encouraged – it’s a sensible idea when the pros of genetic testing outweigh the cons. Genetic testing has potential benefits, whether the results are positive or negative for a gene mutation. Test results can provide a sense of relief from uncertainty and help people to make informed decisions about managing their healthcare.

Cons
Some disadvantages or risks that come from genetic testing can include:

• Testing may increase anxiety and stress for some individuals.
• A negative impact on family and personal relationships.
• You might not be eligible for health insurance contributions if you do not fit certain criteria required for testing.
• The result of any genetic test does not mean that you will definitely not get a certain disease. It simply means you don’t have the genetic variant for that particular disease.
• Genetic testing can provide only limited information about an inherited condition. The test often cannot determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress and worsen over time.
• Another major limitation is the lack of treatment strategies for many genetic disorders once they are diagnosed.
• Privacy concerns plague everyone in today’s digital world, which is also true for genetic testing. Who controls the info? Who has access?
• Ethical considerations are also an issue. How will the test results be used? Could it be used against you? Could it affect your personal finances, insurance, long-term care and disability?
• Whilst qualified interpretation of results is essential, not everyone is qualified to interpret results. Direct-to-consumer kits can prove especially problematic for this reason.
• Testing does not eliminate a person’s risk for cancer.
• Results in some cases may return inconclusive or uncertain.

Pros of Genetic Testing

• If you already have a disease, understanding whether you have a genetic variant could inform treatment protocols.
• The right genetic test for the right individual might provide information that would allow a doctor to recommend a different type of treatment to that which was considered at the outset.
• If you don’t already have a disease, knowing you have a genetic variant for a particular illness could lead you to make positive lifestyle and/or behavioural changes to help lower the risk of getting that disease.
• A genetic test can help diagnose a rare health condition in a child and help you understand whether an inherited health condition may affect you, your child or another family member, and help you decide whether to have children.
• To show if you are at higher risk of getting certain health conditions, including some types of cancer, guide doctors in deciding what medicine or treatment to give you.
• Guide doctors on whether you’re able to join a clinical trial

A 2012 research from Harvard Medical School showed “during the first 75 years of life, genes have a relatively small influence on longevity, accounting for only 20% to 25% of the reasons you live to that age^[12]. Not smoking, eating healthfully, getting plenty of exercise, and limiting alcohol consumption matter the most.”^[13]

Cost
The cost of genetic testing in the US can range from under $100 to more than $2,000, depending on the nature and complexity of the test. The cost in the UK is less and genetic testing is free on the NHS if you are referred for it by a hospital specialist. You will generally only be referred if you have a suspected genetic health condition or if you have a particular type of cancer. 

It might be important to find out how the results of a genetic test would affect your future health insurance cost and availability before going ahead with testing.

What Tests are Available?
The NHS website has a section dealing with predictive genetic tests for cancer^[14].

Genetic testing involves an examination of your DNA, the chemical database that carries instructions for your body’s functions. Genetic testing can reveal changes (in this context, called mutations) in your genes that may cause illness or disease in the future. Despite providing important information for diagnosing, treating and preventing illness, there are limitations. For example, if you’re a healthy person, a positive result from genetic testing doesn’t always mean you will develop a disease. Conversely, in some situations, a negative result doesn’t guarantee that you won’t have a certain disorder.^[15]

Genetic testing of plants and animals can be used for similar reasons as in humans (to assess relatedness/ancestry or predict/diagnose genetic disorders)^[16], to gain information used for selective breeding,^[17] or for efforts to boost genetic diversity in endangered populations.^[18]

Mayo Clinic provides a list^[19] of different types of genetic/DNA tests used to identify changes in DNA sequence or chromosome structure:

• Diagnostic testing: genetic testing can show if you have the suspected disorder indicated by diagnosis.
• Presymptomatic and predictive testing: If you have a family history of a genetic condition, getting genetic testing before you have symptoms may show if you are at risk of developing that condition.
• Carrier testing: is used if you have a family history of a genetic disorder- you may choose to have genetic testing before having children.
• Pharmacogenetics: is used when a particular health condition or disease is suspected. This testing may help determine what medication and dosage will be most effective and beneficial.
• Prenatal testing: during pregnancy, tests can detect some types of abnormalities in the baby’s genes. Down syndrome and trisomy 18 syndrome are two genetic disorders often screened for as part of prenatal genetic testing.
• Newborn screening: this is the most common type of genetic testing. All US states require that newborns be tested for certain genetic and metabolic abnormalities that cause specific conditions.
• Preimplantation testing: (aka preimplantation genetic diagnosis) – used when attempting conception through in vitro fertilisation.

MedlinePlus also provides a list of tests^[20]:

• Molecular Tests: These tests determine the order of DNA building blocks (nucleotides) in an individual’s genetic code – a process called DNA sequencing. These tests can vary in scope
  • Targeted single variant: Single variant tests look for a specific variant in one gene.
  • Single gene: Single gene tests look for any genetic changes in one gene.
  • Gene panel: Panel tests look for variants in more than one gene.
  • Whole exome sequencing/whole genome sequencing: These tests analyse the bulk of an individual’s DNA to find genetic variations.
• Chromosomal tests: used to analyse whole chromosomes or long lengths of DNA to identify large-scale changes.
• Gene expression tests: look at which genes are turned on or off (expressed) in different types of cells.
• Biochemical tests do not directly analyse DNA but study the amount or activity level of proteins or enzymes that are produced from genes.

Sources and Further Reading

• https://www.centralfifetimes.com/news/20027373.nhs-must-introduce-genetic-testing-stop-medicines-harming-patients/
• https://www.reuters.com/article/idUSL7569467
• https://www.webmd.com/a-to-z-guides/news/20190228/danger-abounds-when-meds-and-your-genes-dont-mix
• https://www.bbc.co.uk/news/health-50069155
• https://www.ncbi.nlm.nih.gov/books/NBK236044/
• https://www.theguardian.com/science/2022/mar/29/experts-push-for-genetic-testing-to-personalise-drug-prescriptions
• https://www.partnermd.com/blog/genetic-testing-pros-cons
• https://healthblog.uofmhealth.org/health-management/pros-and-cons-of-genetic-testing-what-to-know-before-you-go
• https://medlineplus.gov/genetics/understanding/testing/benefits/
• https://www.health.harvard.edu/blog/gene-testing-to-guide-antidepressant-treatment-has-its-time-arrived-2019100917964
• https://committees.parliament.uk/committee/135/science-and-technology-committee/news/156039/mps-urge-government-to-review-regulations-for-directtoconsumer-genetic-testing/
• https://www.dnanudge.com/index.php
• https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2008/06/ethical-issues-in-genetic-testing
• https://www.futuremedicine.com/doi/10.2217/pme-2017-0001
• https://www.thermofisher.com/uk/en/home/clinical/precision-medicine/precision-medicine-learning-center/precision-medicine-resource-library/precision-medicine-articles/pharmacogenomics-ready-mainstream.html
• https://www.nature.com/scitable/topicpage/pharmacogenomics-and-personalized-medicine-643/
• https://www.cdc.gov/genomics/disease/pharma.htm
• https://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/understanding-pharmacogenomics
• Pharmacogenomics in the UK National Health Service: Opportunities and Challenges: at https://discovery.ucl.ac.uk/id/eprint/10114632/3/Bramon_NHS%20Report%20for%20publication%203_MP.pdf
• https://www.nhs.uk/conditions/genetic-and-genomic-testing/
• https://www.mayoclinic.org/tests-procedures/genetic-testing/about/pac-20384827
• https://en.wikipedia.org/wiki/Genetic_testing
• https://medlineplus.gov/genetics/understanding/testing/types/
• https://www.nhs.uk/conditions/predictive-genetic-tests-cancer/
• https://geneticalliance.org.uk/information/service-and-testing/benefits-and-risks-of-genetic-testing/

Caution: No advice is implied or given in articles published by us. This guide is for general interest only. It should never be used as a substitute for obtaining advice from your Doctor or other qualified clinician/medical practitioner. The facts are believed to be correct as at the date of publication, but there may be certain errors and omissions for which we cannot be responsible. The hyperlinks were valid at the date of publication.

1. Source: ThermoFisher at https://www.thermofisher.com/uk/en/home/clinical/precision-medicine/precision-medicine-learning-center/precision-medicine-resource-library/precision-medicine-articles/pharmacogenomics-ready-mainstream.html ↑

2. Source: https://www.nature.com/scitable/topicpage/pharmacogenomics-and-personalized-medicine-643/ ↑

3. Source: https://www.cdc.gov/genomics/disease/pharma.htm ↑

4. Source: https://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/understanding-pharmacogenomics ↑

5. See: https://discovery.ucl.ac.uk/id/eprint/10114632/3/Bramon_NHS%20Report%20for%20publication%203_MP.pdf ↑

6. Source: Spear BB, Heath-Chiozzi M, Huff J. Clinical application of pharmacogenetics. Trends Mol Med, 2001; 7(5): 201-20. ↑

7. Source: Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004; 329(7456): 15-19. ↑

8. Source: https://www.england.nhs.uk/medicines/value-programme ↑

9. Excerpted from: https://discovery.ucl.ac.uk/id/eprint/10114632/3/Bramon_NHS%20Report%20for%20publication%203_MP.pdf ↑

10. Source: BBC, 17^th October 2019, at: https://www.bbc.co.uk/news/health-50069155 ↑

11. Sources: https://www.partnermd.com/blog/genetic-testing-pros-cons, https://healthblog.uofmhealth.org/health-management/pros-and-cons-of-genetic-testing-what-to-know-before-you-go, https://medlineplus.gov/genetics/understanding/testing/benefits/ ↑

12. Source: https://www.health.harvard.edu/blog/living-to-100-and-beyond-the-right-genes-plus-a-healthy-lifestyle-201201114092 ↑

13. Source: https://www.nhs.uk/conditions/genetic-and-genomic-testing/ ↑

14. At: https://www.nhs.uk/conditions/predictive-genetic-tests-cancer/ ↑

15. Source: https://www.mayoclinic.org/tests-procedures/genetic-testing/about/pac-20384827 ↑

16. Source: “UC Davis Veterinary Genetics Laboratory | Animal DNA testing | forensic testing | animal genetic research and diagnostics”. www.vgl.ucdavis.edu ↑

17. Source: “Selective breeding and gene technology”. http://www.bbc.co.uk. ↑

18. Source: Hunter, Margaret E.; Hoban, Sean M.; Bruford, Michael W.; Segelbacher, Gernot; Bernatchez, Louis (2018-07-17). “Next‐generation conservation genetics and biodiversity monitoring“. Evolutionary Applications. 11 (7): 1029–1034. doi:10.1111/eva.12661. ISSN 1752-4571. PMC 6050179. PMID 30026795. ↑

19. Source: https://www.mayoclinic.org/tests-procedures/genetic-testing/about/pac-20384827 ↑

20. At: https://medlineplus.gov/genetics/understanding/testing/types/ ↑