Ethics and data protection
Ethics and data protection
Use of PGx profiles has been criticised by those who argue that manufacturers and sellers overstate their usefulness and are profiting from their sales at a time when the clinical benefit is unclear.
There is clearly some considerable potential but apart from specific targeted testing (such as the carbamazepine example highlighted earlier), much research still needs to be done to prove the scientific validity of wider profiling.
It could even be argued that the value of these tests has not lived up to the initial promise. An example is hypertension where, although it is known that individuals may respond differently to various drug classes, doing genetic tests has as yet not shown much benefit in identifying responders versus non-responders and in improving clinical outcomes.
Another issue relates to how individuals’ DNA samples are used and who ‘owns’ them. This raises concerns about data protection, confidentiality, who may get access to the DNA results, and how testing is regulated. Furthermore, these results may convey more information than that just related to drug metabolism. An extreme example is finding genetic abnormalities that have major health implications.
Research continues with warfarin...
Another area where there is a wide range of responses to different treatment doses concerns warfarin. Some people require very low doses to achieve anticoagulation; others need extremely high doses. Alongside several other factors, which include diet, there are two PGx explanations:
- Warfarin is metabolised mainly by the cytochrome P450 enzyme CYP2C9, which is strongly influenced by genetic variation in expression (genetic polymorphism affecting pharmacokinetics)
- Even with comparable plasma warfarin levels, some individuals show super-sensitivity and, conversely, some show resistance to the anticoagulant effects. This is because warfarin acts by inhibiting vitamin K epoxide reductase complex 1 (VKORC1), which is also a polymorphic enzyme (affecting pharmacodynamics).
Initially it was thought that combining tests for these two enzymes would provide a useful method to predict the appropriate dose of warfarin for most people. However, so far, research (including real-life use in hospital warfarin clinics) has not demonstrated benefit above and beyond careful initial dose titration (e.g. using computerised decision support). This is thought to be because 60 per cent of the variability in warfarin dose and response is due to other factors, many non-genetic, so any additional benefits from testing may be marginal for many people.
Conclusion
Although there is increasing interest in PGx tests, those which can be used to alter clinical decision-making and are clearly proven to improve clinical outcomes are relatively few in number.
Perhaps the most important role of pharmacists at this current time remains to advise on the place of commercial PGx tests, their usefulness, suitability and limitations. Pharmacogenomic testing is an exciting, developing field and NHS screens are becoming more common. Precision medicine will be an increasingly important aspect of all prescribing in the future.