Henry Ford is famously quoted as saying, when his first Model T Ford rolled off his factory line, “you can have any colour you want, as long as it is black”.
It is a quote I often use in my talks and it always elicits the same response — “why is this quotation relevant to personalised medicine?” The answer is that, for the past 40 years, modern medicine and the pharmaceutical industry have taken the same view as Henry Ford, in that we treat disease in a ‘one size fits all’ manner.
Indeed we have often treated patients as being the same, regardless of their ethnic background and, to some extent, age (with children and babies being treated poorly in this respect). In fact, with the exception of minor dose modifications for patients in Japan and South East Asia to allow for body weight adjustment, the majority of new medicines have been introduced to the market with a narrow number of dosage strength options.
With the advent of genomics, we have realised that some patients will respond to a medicine differently to others. The much quoted example of this is the medicine Herceptin (trastuzumab; Roche) which is used for the treatment of breast and stomach cancer. Around one in five people with breast and stomach cancer exhibit an unusually high level of the human epidermal receptor type 2 (HER2). Herceptin exerts its therapeutic effect by blocking HER2 and thus supressing tumour growth. Using a diagnostic test, it is possible to determine if a breast or stomach cancer patient has high levels of HER2 and, if so, they can be treated with Herceptin, which is likely to be an effective therapy. For patients with normal levels of HER2, however, Herceptin will not be effective and an alternative treatment must be used.
So you might think that the answer to patient diversity is fairly simple — use a diagnostic test to group (or stratify) patients in order to give ‘the right drug, at the right dose, at the right time’ and thereby optimise their treatment.
Well, you would be wrong. The issue you have forgotten is that patients are rarely prescribed a single drug. For example, a type 2 diabetic patient with hypertension or dyslipidaemia or both is likely to be taking a cocktail of medicines, often as many as 15 tablets or capsules per day.
If it were possible to find a way of personalising or customising the combination of drugs patients take to provide them with an individualised treatment regimen then I am convinced that it would be feasible to improve medicines use, improve medicines adherence and improve clinical outcomes.
One such attempt to solve this problem has been made by Wald and Law, who developed a polypill. This polypill contained four drugs — simvastatin to lower cholesterol, and hydrochlorothiazide, losartan and amlodipine to lower blood pressure. When this polypill was tested in 2,000 people in India and Europe (the so-called UMPIRE trial) it was found to be advantageous. Some 86% of people given the four-in-one polypill were compliant with their medicine, compared to only 65% of those who received the standard treatment consisting of four individual medicines. Furthermore, the trial showed that people taking the polypill experienced slightly better outcomes in blood pressure and cholesterol levels.
So is the answer simply putting all the drugs a patient is taking into a single tablet? Could we create a polypill for different diseases? Unfortunately it is not as simple as that because there are two competing forces. One is to minimise the number of medicines a patient takes, the other is to provide maximum flexibility.
Let us consider the preparation of a polypill. To produce a single tablet, we need to fix the combination of drugs as well of the dose of each drug. For prescribers this greatly restricts their choices for their patients. As an example of the problem, one clinician may favour prescribing a patient simvastatin while another prefers atorvastatin, and each may want to give the patient different dosages. Preparation of a single polypill does not allow this flexibility. It is not possible for the pharmaceutical industry to provide a polypill for every single possible drug-dosage combination because companies could not manufacture and store all the possible combinations. And just think of the cost.
So what is the answer? Perhaps we can learn from the past. At one time, pharmacists used to personalise their patients’ medicines every day when compounding and dispensing a medicine for a patient. In the UK today, these compounding skills are seldom used, but across much of the world, particularly in North America, such individualised compounding and dispensing is common place.
The pharmaceutical industry, working with healthcare practitioners and regulatory agencies, must provide a common technology platform that will allow the building of a polypill to suit a patient’s individual needs. I have been working on a prototype technology, the MyDOSE platform (GSK), which could offer this kind of solution. Using the MyDOSE platform, pharmaceutical companies provide special strips of drugs at varying doses (think of Lego bricks) to pharmacies where there is a special purpose assembly machine. The idea is straightforward — when a pharmacist gets a prescription to dispense, the required strips are inserted into the assembly machine which moulds them together and ejects them as a single ‘tablet’.
Prototypes of MyDOSE have been developed and tested, although there is still a long way to go before the technology is common in a pharmacy. But, in the modern world, where it is predicted that one in three women and one in four men will live to 100 years of age, we must find a way to customise our medicines to provide true personalised drugs from our local pharmacy.
After all, I can have my coffee black, white, black with sugar, white with sugar, white but strong with one sugar and so on. Why should we restrict the way we supply our medicines to patients?