Genetic tests which aim to provide information on individual responses to drugs are being regulated in a confusing and possibly dangerous way, claim UK researchers.

The UK Pharmacogenetics Study Group, a group of collaborating scientists from Sussex, Plymouth, Cambridge, York, Exeter and Nottingham universities, have issued a call for changes to EU regulations to protect patients.

Pharmacogenetics is the study of genetic variation and its influence on people's different responses to drugs. Increasingly, clinicians are performing pharmacogenetic tests in an attempt to predict how a patient will react to treatment, both in trials and for marketed drugs.

But a new study has concluded that the lack of regulation of these tests, coupled with the fact that they offer only incomplete information, could pose serious risks to patients.

"Pharmacogenetic tests can tell you the extent to which a particular person can metabolise a drug," explains Dr Michael Hopkins, a Research Fellow at SPRU Science and Technology Research at the University of Sussex. "But they don't ensure that a person won't have a negative reaction, because not all toxic reactions are due to genetic traits.”

Similarly, he goes on, these tests can tell you if someone has a mutation that may be relevant to a condition. “But they don't tell you whether or not this link is tight enough to base prescription information on it. Importantly, this latter step is the bit that isn't covered by regulation. If tests are not fully validated, people will be prescribed drugs that are inappropriate," he says.

"The problem is that pharmacogenetic tests are lumped together with the regulations of all the other genetic tests," says Dr Adam Hedgecoe, a senior lecturer in the sociology department in the University of Sussex. "European legislation classifies pharmacogenetics as low risk, meaning that they are not overseen by regulatory authorities."

A degree of discrimination needs to be introduced into the European legislation, to reflect the fact that pharmacogenetic tests are not necessarily low risk and to acknowledge that the safety or risks associated with these tests must be judged in their own terms, says Hedgecoe.

“As far as I am aware, we are the first to raise the issue of the danger of lumping pharmacogenetic tests with other genetic tests." says Hedgecoe.

The group describe their concerns in a new report, entitled Policy Issues in Pharmacogenetics.

Genetic testing in trials

The most widespread use of pharmacogenetics in current clinical trials is for internal purposes, to exclude those drugs where there is a wide variation in response according to common genotypes such as cytochrome P450.

But often clinical trials involve the sampling of DNA, which is then stored for unspecified future pharmacogenetic purposes.

“It is notable that while there has been considerable public and policy debate over the development of public or partly public DNA databases such as UK Biobank, with concerns often being raised about commercial access, there has been little or no public discussion over the commercial development of similar DNA banks through the collection and long term storage of samples in pharmacogenetic clinical trials,” notes the report.

The pharmaceutical industry has attempted to develop standardised policies on DNA sampling, but crucially the issue of pharmacogenetics is not covered specifically by Europe’s Clinical Trials Directive, and there is considerable variation between EU member states on how this is regulated.

The UK, for example, has no regulations specifically governing the sampling of DNA in clinical trials, while in Sweden investigators are required to seek permission for secondary research, i.e. analyses not previously divulged around the time of collection.

“One consequence of this variation is that firms working in a number of EU member states suggest that Europe is becoming an increasingly difficult research environment for studies sampling DNA for storage,” concludes the report, and this may throw up a barrier to international studies of pharmacogenetic tests intended for use on broad patient populations.