The benefits of personalised medicine are increasingly recognised around the world, enabled by advances in our ability to obtain and analyse information from genomic and other biomarkers and combine this with other medical information.
Personalised medicine can affect many different aspects of healthcare, including the personalisation of risk prediction and disease prevention. Main areas of current benefit are in rare diseases, cancer and pharmacogenomics, a term that refers to genetic influences on variability of drug response.
Unpacking different drug responses
Medicines are integral to treating disease, but two people with the same condition may respond very differently to the same medicine. There are many reasons for this, with which health professionals are well acquainted. Doctors and pharmacists are skilled in adjusting for age, sex, body mass, interactions with other drugs a patient may be taking, other medical conditions the patient may have, lifestyles, and so on.
Another influence is pharmacogenomic variation: the impact of genetic factors that control how the body processes (metabolises) different drugs.
Some people respond better to a given drug or dosage than others. Some may metabolise a drug so fast that a normal dose has little or no effect, whilst others may be so slow to break the same drug down that they are exceptionally sensitive to the effects it causes. For these people a normal dose would be harmful. Between a quarter and a half of observed variation in drug response may be the result of genetics.
The cost of failure
Adverse drug reactions (ADRs) are a huge, but largely invisible, problem in healthcare. At worst, they kill people. More commonly, a patient may receive a drug that doesn’t work for them, wasting time and money until this becomes apparent and an alternative drug is prescribed.
In the UK alone, over 6% of hospital admissions are caused by ADRs, at an estimated cost of approaching £500 million; in the US, the corresponding figure is around $2 billion. These figures don’t take into account the additional economic impact of ineffective medications, or of mild side-effects. Or the human cost on top of that.
We definitely need to do better with our drug use. Efforts to make the most of increasing capacity to test for known pharmacogenetic variants, could offer health and - depending on the cost of testing - economic benefits.
The UK is actively engaged in such efforts, and in gathering evidence to determine whether all citizens should have a ‘pharmacogenomic profile’ attached to their medical records, as set out in the 2020 National Genomic Healthcare Strategy.
A question of variation
One current limitation to using genomics for healthcare is the lack of population diversity in the data used to understand genomic variation and develop useful tests. Existing databases are drawn predominantly from European and North American populations and may not reflect the genomics of other populations so well.
A new study from the LKS Faculty of Medicine at Hong Kong University has analysed pharmacogenetic variants in the Hong Kong Chinese population. They examined genomic data (exome sequences) from more than 1,100 people and found over 500 rare pharmacogenetic variants predicted to have harmful effects, nearly a hundred of which had not previously been reported. Over 93% of the people had at least one variant that could significantly affect their response to drugs – what is termed an actionable variant - suggesting the need to use a different dose or drug.
The research team, led by Prof Brian Chung, also looked at 133 well known actionable pharmacogenetic variants that affect sensitivity to 36 drugs, such as simvastatin (a drug to reduce cholesterol) and clopidogrel (a blood-thinning drug). Using drug prescription data taken from the public healthcare system, the researchers calculated that in 2019 alone more than a million Hong Kong patients had received prescriptions of these drugs, representing over 13% of prescriptions and nearly 25% of the total spend on medicines.
Prof Chung’s team discovered that over 96% of the Hong Kong population have at least one of the pharmacogenetic variants known to affect the response to these drugs, suggesting that pharmacogenetic testing to guide prescription of such drugs would indeed be useful.
However, whilst the overall frequency of pharmacogenetic variants was a similar level to that of other populations, the pattern of variants – those that were most common - was markedly different.
Combined with the discovery of new pharmacogenetic variants also common in the local population, the researchers concluded that clinical guidelines for pharmacogenetic testing should be customised for patients from different ethnic groups. It seems the mantra of personalised medicine – one size does not fit all – should be applied to populations as well as individuals.
Personalising health policy
This study adds valuable knowledge about genomics and pharmacogenomics in the Hong Kong population, which is predominantly Han Chinese. There are well over a billion people of Han Chinese descent in mainland China, and many millions in other countries around the world, so this is significant.
Health professionals and policy-makers are already well attuned to the variable healthcare needs of different groups within populations, especially ethnic groups, and this often informs local provision. At a national level, understanding the genetic variation present in a population is equally important for optimising relevant clinical guidance.
The future of pharmacogenomics
Pharmacogenomics is gradually entering the healthcare in countries such as the US, Australia and the UK. But we are some years off from medical records routinely showing our first choice and dose of certain drugs. How high a priority this should be for already struggling health services is debatable.
Anyone who has had to make repeated visits to a warfarin clinic to get their dose right will appreciate the saving in time and effort pharmacogenomic testing could offer. But for most of us, it is hard to imagine the impact of pharmacogenomic testing - we don’t generally see features or interviews with people who have suffered from dangerous drug reactions.
Nevertheless, illnesses will be averted; lives will be saved; personal and health service resources protected. This is something that could deliver consistent, real benefits for all of us – and using the best, most tailored guidance for different populations may offer additional value.