Abstract
Since the Human Genome Project was completed and published in 2003, personalized (or precision) medicine has gradually been moving forward to improve health care. The cost of sequencing the human genome has dropped considerably from millions to thousands of pounds through rapid technical advancements. This means that the cost has dropped to a point where people will soon be able to possess their own genetic information on a ‘smart card’ or memory stick. 1 It is thought that the future patient will be able to walk into their clinician's office and present their genetic information so that the right treatment can be given at the correct dose for a condition with few adverse drug reactions or lessened possibility of treatment failure. A recent announcement by the UK government has put the future patient into the present reality by providing programme funding to the NHS to map the genetic makeup of 100,000 people in England. Patients with cancer and certain rare disease will voluntarily have their DNA mapped to identify key genetic components that will aid in medical treatment. 2
Link between personalized medicine and the human gene
Drug metabolism and physiologic action in the body depends on particular enzymes and targets that are under genetic control. 1 Pharmacogenetics is the science of the genetic differences in metabolic pathways which can affect the response to drugs in the body in terms of a positive physiologic effect or development of adverse events. Identifying the patients who have enhanced or decreased enzymatic and target activity increases the likelihood of effective treatment and patient satisfaction. The principles underpinning personalized medicine are established, promising to make medicines safer and more effective by individualized therapy determined by a patient's genetics (genotype). The principle assumes that a patient's response to a drug is intricately linked to their genotype. 3 Pharmacogenetics may deliver ‘better’ medical treatment by examining the differences in genetic determinants instead of the ‘one-size-fits-all’ approach that has been the basis of medicine thus far.
In reality, however, doctors have long been practising ‘personalized medicine,’ taking account of many characteristics of patients that determine drug response, such as age and sex, family history, renal and hepatic functions, other medications and social habits, such as smoking. Renal and hepatic function can affect the elimination and accumulation of a drug and, therefore, dictate the need for individualized selection of a drug and its dose. Patient behaviour and the ability to adhere to treatment directions are also considered when a decision to prescribe is taken. Therefore, personalized medicine should not only include the genetic makeup of the patient but also the demographic, behavioural and social factors that affect drug therapy.
Pharmacogenetic and personalized medicine research
At present, the effective dose of a medicine has been established through clinical trials. A limitation of this ‘one-size-fits-all’ approach is where an established dose has to work in diverse patients such as elderly and young, male and female and all ethnicities. 4 Ironically, the major methodological barrier to more individualized therapies is not a paucity of predictors of outcomes and effects; it is that patients have so many attributes that potentially affect risk and response to treatment that subgroup analysis is statistically not feasible. We currently lack a consistent analytical approach that informs how a patient's multiple attributes combine to affect the fundamental determinants of the desirability of treatment – that is, the individual's risk of bad outcomes in the absence of treatment versus that individual's risk if treated.
Personalized medicine provides doctors with a means to increase the benefits of treatment yet decrease the risk of adverse events. However, there seems to be a slow adoption in health care. A study by Stanek et al. 5 surveyed the knowledge and extent of use of pharmacogenetic testing among doctors in the USA and found that while 97.6% agreed that genetic variations may influence drug response, only 10.3% felt adequately informed about pharmacogenomics testing, 12.9% had ordered a test in the previous 6 months and only 29.0% had received any education in the field. 5 Lack of knowledge of pharmacogenetics and testing may be holding back the progression of personalized medicine in health care.
Implications for health services research and policy
Important implications of personalized medicine for health services research are the issues of privacy, autonomy and ethical research design. Pharmacogenetic information used for the treatment of a particular disease may be aggregated for research. However, there are ethical issues about the secondary use of genetic information for the development of drugs, as occurs with clinical trials where patients should give informed consent and possibly be paid for their participation in the research. Researchers may not contact patients for further information such as social variables (smoking status) or co-morbid diseases that should be included in any analyses as confounding variables. Therefore, policies must be in place to allow for the genetic information to be shared in a way that protects the confidentiality of the patient and the right to opt-out of further research use. It is vitally important to the patient that their genetic information is kept private and away from insurance companies or the government. The information may be used to identify people who could be genetically pre-disposed to diseases like cancer or diabetes, which may affect their insurance coverage, set policy rates, driving licence limits or future health care.
In the UK, there is a large database of information, including genetic, that has been collected prospectively from people aged 40–69 in England, Scotland and Wales. 6 The UK Biobank has an extensive collection from a half a million people on biological information including blood, urine and saliva for long-term storage and details of blood pressure, lung function, bone density and other clinical features. Patients understand that this information is being used for the present and future research and are willing to have their health followed for the next 30 years. This prospective collection allows patients to decide how and if their information could be used and be assured that confidentiality is maintained.
Conclusions
The cost of sequencing a patient's genome is dropping significantly to a point where the risk/benefit ratio will favour genetic mapping for everyone. It is thought that through greater effectiveness of drugs and avoidance of unwanted side-effects, there could be reduced health spending in the long run. 7 However, we need to ensure that equity and access are also taken into account. For health services and policy research, the development of personalized medicine could strengthen the methodology of some research though it also presents complex analytical challenges. The development of personalized medicine is not the future anymore, but the present, and researchers have to prepare to take on the challenges ahead.