What would medicine be without drugs? But are these drugs being used optimally today? Not at all, as we now know thanks to the findings of molecular medicine. Because for the use of these drugs, it is important to observe two aspects: the disease and the patient. Only slowly is it becoming possible to more and more include patient-relevant information into a treatment decision.
Before a drug is authorized for use in human beings, it is extensively tested - initially in the most varied biochemical-pharmacological models in test-tubes or in an organ bath, then in diverse animal models and finally on test persons and patients. This tiered approach allows for reliable conclusions regarding the effectiveness and tolerability of the drug. And only when a benefit/risk analysis is clearly in favour of the benefits, will the drug be awarded access to the market via licensing by international or national authorities.
However, these statements are somewhat ambiguous in their details, since they are based on the formation of a more or less projected Gaussian distribution. This is what we have become accustomed to, because there is no alternative. However, were a large enough test population selected, this would show some radical “outliers”. Those affected by such a marginal population can, in some cases, have major problems with such a drug. This is because swings in the direction of “ineffectiveness” are just as possible as swings in the direction of individual overdose during, an in principle, correct application, which can be expressed as intolerance to the point of acute toxicity.
With the rapidly increasing demand for security in our society in recent years, such individual swings, in terms of safety and efficacy, can place a drug itself at risk. An increase in reports of insufficient efficacy, or side effects, though low in number yet serious in effect can nowadays quickly lead to the loss of the licence. It is, therefore, in the interest of patients, as well as the pharmaceutical industry, to take measures to make such fluctuations in terms of efficacy and tolerability of a drug predictable and thereby preventable.
The causes of these individual deviations from the norm are differences in the genetic makeup of the patients. These can be such that, due to the possibility of physiological “detours”, the properties of a drug are cancelled out. They can also affect the functional units (enzymes and transporters), which naturally modify the active substance or grant the drug access to the target structure.
Today it often possible, in principle, to recognise these deviations, respective measures operate under the heading “stratified medicine”. The consequences, which will result in the use of this technical potential, will amount to a paradigm shift. In due time we will see a change, from the treatment of a disease to the treatment of a patient with a specific genetic makeup.
Many examples have been listed where already today a therapy could be significantly optimised, if therapy decisions were not only based on disease-related parameters but rather the patient-specific genetic parameters were also included. Diagnostics – and more than ever genetic diagnostics – receive a new quality here: the traditional terrain of disease-related diagnostic investigation will be supplemented by diagnostics that will reveal whether and how drugs may act on a certain disease.
These new prospects would make good, existing therapies in many ways even better - particularly for patients who, based on individual parameters, do not fall within the crown region of a Gaussian distribution of the outcome of a clinical efficacy study.
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