Genetic tests that improve drug effectiveness are going neglected, warns expert

Genetic tests that could greatly improve the effectiveness of drug therapy for a wide variety of conditions are being underused or ignored, a leading expert says.

Advances in the field of pharmacogenetics - the study of the genetic differences that influence how we metabolise and respond to medicines - have led to diagnostic tests that have been slow to gain widespread use, despite clear advantages.

Dr Ron van Schaik, associate professor and clinical chemist at the Erasmus Medical Centre in Rotterdam, the Netherlands, founded one of the first hospital-based pharmacogenetics laboratories in 2005. In the beginning, pharmacogenetic tests were not widely available. That has changed, and evidence of their clinical usefulness is also growing.

Nowadays a simple DNA test can identify patients who, for example, require 10 to 50 percent of the standard dose of a particular drug to avoid severe side effects. This is true for acute lymphatic leukaemia patients carrying variants of the TPMT gene receiving 6-mercaptopurine treatment.

Other tests indicate which patients are unlikely to respond to treatment at all because their bodies are unable to activate a drug, as is the case with the anti-blood clotting drug clopidogrel which needs activation by CYP2C19, or the cancer drug tamoxifen, which is activated by CYP2D6. In the case of HIV (human immunodeficiency virus) patients, a simple screen for the HLA (human leukocyte antigen)-B*5701 gene variant shows which patients are most likely to suffer severe side effects and so should be prescribed a different drug.

But widespread clinical implementation of these tests has been slow. Dr van Schaik says that this is partly because previously genetic tests have been used mostly to diagnose severe diseases. 'The general notion that you can do DNA analysis without looking for a disease is novel, and apparently is an issue', says Dr van Schaik.

'Genetic tests have mostly been done for rare diseases in clinical genetic centres and this also induces the belief that the test would be costly', adds Dr van Schaik. 'But a pharmacogenetic test can be ten times cheaper than a genetic test for a rare congenital disorder'.

Nonetheless, health economics can remain a barrier to widespread adoption of the tests. 'In our hospital', Dr van Schaik explains, 'laboratory tests are paid for by the department whereas the drug costs go directly from the hospital budget. So the economic benefit of a pharmacogenetic test is not directly felt by those requesting the test'.

The implications of pharmacogenetics can be considerable. For example, over 50 percent of all drugs prescribed are affected by common variations in the cytochrome P450 enzymes CYP2D6, CYP2C9 and CYP2C19. The effectiveness of such therapies may well be enhanced by applying pharmacogenetic information.

Scientific literature on pharmacogenetic testing has grown greatly in the last decade. In order to keep up, a group of experts in the Netherlands, including Dr van Schaik, has started an initiative to perform regular reviews of the literature and publish evidence-based pharmacogenetic dose recommendations (the KNMP/WinAp group). These recommendations are accessible to all pharmacists in the country, and are now also available online.

'If you have one particular gene that affects the metabolism of 50 drugs then practical information is key', says Dr van Schaik. 'Just knowing what genotype a person has is not enough, you need to know what you should do with that information. Creating this nationwide system enables people to interpret the test data and see if the medication they're prescribing is compliant with the genotype'.

Dr van Schaik discussed his research in a presentation 'Clinical Implementation of Pharmacogenetics: A Seven-Year Experience' given at the British Society for Human Genetics Annual Conference on Monday 17 September 2012 at the University of Warwick.