Personalised medicine
Viva la revolution

Over the next few decades we will witness a major change in the way medicine is practised, with diagnosis and treatment being tailored to suit each individual’s unique genetic profile. This transformation is already underway and it promises many things, not least of which is a significant improvement in the health outcomes for patients. Callan Emery reports.

There’s a revolution taking place in medicine. It is a transformation that is evolving on the back of rapid advances in genetic research, innovations in molecular medicine and the development of sophisticated information technology. What is being called ‘personalised medicine’ – that is, healthcare that is tailor-made for the individual – is being hailed as a new era in medicine, which holds tremendous promise for patients, medical facilities and researchers alike.

This view of personalised medicine has been around for several years, however it is only in the past few years that it has started to grab headlines in the public media, largely as a result a handful of organisations, mostly linked to academic medical institutions, advocating its benefits to healthcare. One such organisation is the US-based Personalized Medicine Coalition.

They point out that personalised medicine stands to transform healthcare over the next several decades. “New diagnostic and prognostic tools will increase our ability to predict the likely outcomes of drug therapy, while the expanded use of ‘biomarkers’ – biological molecules that are associated with a particular disease state – could result in more focused and targeted drug development,” says the Coalition.

With the combination of genetic profiling, molecular analysis and the development of highly specific molecular and genetically targeted drugs, physicians will be able to determine a patient’s susceptibility to certain diseases, detect diseases much earlier and provide treatments that are tailored to the individual’s unique genetic and molecular make-up.

Physicians will be able to select the type and dose of medication best suited to that individual resulting in improved health outcomes and less drug-related adverse events for patients.

Felix Frueh, PhD, associate director for genomics in the United States Food and Drug Administration’s (FDA) Office of Clinical Pharmacology and Biopharmaceutics, said: “The goal of personalised medicine is to get the best medical outcomes by choosing treatments that work well with a person’s genomic profile, or with certain characteristics in the person’s blood proteins or cell surface proteins.”.

However, in personalised medicine, genetic information isn’t usually meant to be used alone to make treatment decisions, but rather is used with other factors such as the patient’s family history, medical history, clinical exam, and other nongenomic diagnostic tests.


The vast majority of genes function exactly as intended: giving rise to proteins that play key roles in biological processes and allow a person to grow and live in their environment. In rare instances, one single mutated or malfunctioning gene leads to a distinct genetic disease or syndrome.

The most familiar of these rare disorders include sickle cell anaemia and cystic fibrosis. Such disorders are termed “monogenic” because a single gene is responsible for their occurrence.

But multiple genes acting together can also influence the development of many common and complex diseases, as well as our response to the pharmaceuticals designed to treat them.

The contribution of several genes to these complex disorders is termed “polygenic.” Often as a result of this complexity, what may appear to be one disease on a clinical level could, on a molecular level, be reclassified as several different diseases, each of which might respond to a different treatment.

Such disease complexity exists for asthma and many forms of cancer. Through molecular analysis of biomarkers scientists can identify these subtypes within a disease.

Biomarker analysis can also help classify sub-groups of patients who have the same molecular variation of the disease, enabling one to monitor its progression, select appropriate treatments, and measure the patient’s response to medication.

But in order to do this drugs specific to certain genetic profiles have to be developed and this has led to the fast emerging field of pharmacogenomics, the combination of pharmacology and genomics.


The incidence of adverse drug events is very high and the hope is that personalised medicine, by tailoring drugs to a person’s genetic profile will significantly reduce this phenomenon.

In the US adverse drug events are the fourth to sixth leading cause of death. The overall incidence is 7%.

Among hospitalised patients 28% have drug-related adverse events, according to a recent paper by Freuh. He points out that the cost of drug-related morbidity and mortality in the US is US$177 billion With the mapping of the human genome complete, research of specific genes, genetic mutations and the traits and characteristics for which they are responsible is advancing rapidly.

Almost on a daily basis there is news of the discovery of the genetic root to some or other disease state. Larry Lesko, PhD, director of the US FDA’s Office of Clinical Pharmacology and Biopharmaceutics noted that there are three aspects in the way pharmacogenomics can be applied. “The first is to help predict the appropriate dose of a drug. The second is to target therapy to a subset of a disease.

This means picking the most effective drug for the disease subset. And the third is to test viral genomics, such as in selecting treatment for HIV based on resistance.” The usual doses of drugs work well for most people. They are sometimes based on weight, age, and kidney function.

But for someone who metabolises a drug quickly, the typical dose may be ineffective and a higher dose may be needed. By contrast, someone who is a slow metaboliser may need a lower dose; the typical dose could cause toxic levels of the drug to build up in the blood.

For example, St Jude Children’s Research Hospital in Memphis, Tennessee, US, when treating children with leukaemia, routinely conducts a genetic test for defects in the enzyme thiopurine methyltransferase (TMPT) – the biomarker.

The defect prevents patients from metabolising the anticancer drug 6-mercaptopurine (6MP). One patient may need a full dose; another, who has a mutation in the gene, may need less than 10% of that dose.

Targeted therapy, the second major aspect of pharmacogenomics, is also referred to as tumour genomics. Tumours have different genomic variations, and genomic tests help doctors to identify cancers that are likely to respond to a particular treatment.

The drugs Gleevec (Imatinib) for chronic myeloid leukemia, Tarceva (erlotinib) for lung cancer, and Herceptin (trastuzumab) for breast cancer are examples of targeted therapy drugs designed to treat specific tumours.

Both Gleevec and Tarceva interact with enzymes called tyrosine kinase inhibitors. Turning off these enzymes prevents the growth of cancer cells. Herceptin targets tumours that produce excess amounts of the HER2 protein, which is produced by the HER2 gene.

Overexpression of the HER2 protein causes a higher rate of cell growth. Before Herceptin is used, tumours must be tested to evaluate the amount of HER2 protein. Until recently, many technologies for examining DNA, proteins and other biomarkers were slow and expensive, which limited the scope and impact of molecular analysis.

But new technologies, such as microarrays and protein arrays, are making biomarker detection much faster and more affordable. Future advances may make it feasible for physicians to screen patients for relevant molecular variations in the office prior to prescribing a particular drug.

Electronic record

Physicians will be able to do this with the aid of another important aspect of personalised medicine, the Electronic Medical Record (EMR).

The EMR is, in essence, a patient’s medical record in digital format, which enables it to be accessed by clinical staff at any location via a medical facility’s digital information network.

There are numerous benefits to this format ranging from the standardisation of clinical procedures and protocols to the automated checking of prescribed drug-drug adverse interactions. A handful of the most advanced healthcare facility networks in the world are in the early stages of implementing the EMR in a way that will make personalised medicine a reality.

One of these is Partners International. Based in Boston, United States, it is one of the world’s leading healthcare networks and includes the likes of Brigham and Woman’s Hospital, Massachusetts General Hospital and Harvard Medical School. Dr James Mongan, CEO Partners International, spoke to Middle East Health about the importance of IT, the Electronic Medical Record and the role it will play in personalised medicine.

He pointed out that this transformation will “lead us into an unprecedented era of medical discovery where personalised and truly preventative medicine become a reality”. An ideal digital hospital information system will integrate all departments in a healthcare network and include the EMR, PACS/RIS, admissions administration, drug prescription data and so on.

The best ones will also have a clinical decision support system. Dr Mongan explained that the EMR is essential for personalised medicine to be effective. He said that Partners International has been developing their homegrown system over the past 10 years. “We’re at a point where nearly all the doctors at the academic centres are networked. We’re about a year and a half from being totally networked,” he explained.

Dr Mongan pointed out that the EMR is important for many reasons – perhaps the most obvious one, and one that is often the butt of many jokes, is that it does away with the notoriously illegible handwriting of physicians and the potentially lifethreatening misinterpretation of their scribbling.

However, the medical record is also important so that each physician knows what the other is doing when treating a patient, he said. He told Middle East Health that there are two features of their system that are very important and cutting edge.

“One is the decision support system. The other is the integration of each patient’s genetic information into the electronic record,” he said. The clinical decision support system is a set of rules, guides and prompts that are built into the electronic system that guides and directs a physician’s practise.

“This ensures a more unified system of best practise across the institution and holds real potential to revolutionise medicine as we know it,” Dr Mongan said. “The real power of and potential in decision support, if properly used, is to reduce the extraordinary and mostly unexplained variance within medical practice, as we have seen in the past decades.

“This variance has a huge impact on cost and quality. However, there is the promise of higher quality and lower costs if best practises are applied more evenly across clinical medicine. Information technology and decision support could finally unlock this puzzle,” Dr Mongan emphasised.

However, it is with the integration of a patient’s genetic information into the electronic record, that personalised medicine really can begin to take shape, Dr Mongan said. “Once your genetic information is part of your medical record it will allow us to know, for example, that you will respond to this drug for hypertension and you won’t respond to that one,” he said. “Across our system electronic medical records will increasingly contain both clinical data and genetic data, both linked to our data repository.

We will be able to use this data to identify patient populations with similar diseases and genetic characteristics, which can lead to exciting new medical discoveries.”

The benefits

The Personalized Medicine Coalition personalised medicine promises three key benefits:

- Better diagnoses and earlier interventions: Molecular analysis could determine precisely which variant of a disease a person has, or whether an individual is susceptible to drug toxicities, to help guide treatment choices. For preventive medicine, such analysis could improve the ability to identify which individuals are predisposed to develop a particular condition – and guide decisions about interventions that might prevent it, delay its onset or reduce its impact.

- More efficient drug development: A better understanding of genetic variations could help scientists identify new disease subgroups or their associated molecular pathways, and design drugs that target them. Molecular analysis could also help select patients for inclusion in, or exclusion from, late stage clinical trials – helping gain approval for drugs that might otherwise be abandoned because they appear to be ineffective in the larger patient population.

- More effective therapies. Currently, physicians often have to use trial and error to find the most effective medication for each patient. As we learn more about which molecular variations best predict how a
patient will react to a treatment, and develop accurate and cost-effective tests, doctors will have more information to guide their decision about which medications are likely to work best. In the future, tests may help identify the one in ten patients who for tumour-specific molecular reasons will benefit from a new lung cancer drug. In addition, testing could help predict the best dosing schedule or combination of drugs for a particular patient.


There are several challenges that may impede this transformation. The Personalized Medicine Coalition points out that the pathway to the development of personalised medicine is marked by the need to identify and address a range of public policy issues and to examine our current approaches to clinical trials, intellectual property rights, reimbursement policies, patient privacy and confidentiality and the standardisation of new diagnostic tools.

The way such issues are managed will affect the evolution of personalised medicine and shape its ability to prevent, diagnose and manage disease. In the US the FDA has begun a number of initiatives to tackle these challenges and advance personalised medicine, specifically with regards to the implications it has on drug development and regulatory review.

Regarding patient privacy and confidentiality, one of the obvious challenges is ensuring the security of the electronic medical record and the patient’s clinical data. But less obvious, although equally important, are the implications of being identified as being predisposed to a certain condition and the psychological and social effects of genetic testing on an individual.

The great promise that personal medicine holds, not only for patients, but also for the advancement of medicine as a whole, will no doubt inspire all stakeholders to overcome these challenges and others yet unforeseen as this wave of transformation builds momentum and carries us into a new medical era.

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