3. Variability in Response

Take a group of people that have all been prescribed the same medicine at the same dose. It is likely that some of these people will respond very well (full responders), but others will not benefit as much (partial responders). In addition, some individuals in the group will not respond at all (non-responders) and others again may suffer from major unwanted side effects (adverse reactions).

Individuals can vary in their response to a medicine both in terms of its efficacy (how well it works) and its safety (whether it causes side effects, or how well it is ‘tolerated’).

The principles of pharmacokinetics and pharmacodynamics are often summarised as:

Many differences between patients’ responses to medicines can be explained by differences in their pharmacokinetics or pharmacodynamics. Also, many genes influence pharmacokinetics and pharmacodynamics. Variation in any of these genes, or in their expression, can therefore be the root  cause of how people respond to a medicine.

A genetic test may provide information about how an individual will respond to a medicine. This means that the most effective medicine and dose can be chosen for this person, and the risk of side effects can be reduced.

For example, a recent study into advanced ovarian cancer has shown that it is possible to separate patients into two groups; 1) those who respond well to platinum chemotherapy and 2) those who do not. Platinum chemotherapy has several common side effects and some of them are serious. Knowing how likely a patient is to respond helps the doctor and the patient to assess whether it is worth risking these side effects. The gene expression ‘signature’ in this case is based on measuring the activity of 227 genes in the tumor. (1)

(1) Dondorp and de Wert 2013. The “1000-dollar genome”: and ethical exploration. European Journal of Human Genetics 21:S6-S26.