Are the same standards applied to genetic and non-genetic tests in clinical medicine? In a review by Munir Pirmohamed and Dyfrig Hughes (download PDF here), the authors “strongly argue that the slow progress in the implementation of pharmacogenetic (and indeed other genetic) tests can partly be explained by the fact that different criteria are applied when considering genetic testing compared with non-genetic diagnostic tests.” They provide a few compelling examples:
There is no regulatory requirement to undertake clinical trials to show that the dosing recommendations for patients with, for example, renal impairment are equivalent in terms of clinical outcomes to those for patients with normal renal function. Indeed, such a stipulation would be impractical and costly, and would never be done during the drug development process, potentially disadvantaging vulnerable patient populations.
Atomoxetine, a drug widely used for attention deficit hyperactivity disorder, is metabolized in the liver by CYP2D6. The SmPC for atomoxetine states that the dose should be reduced by 50% in patients with hepatic impairment (Child-Pugh class B), as drug exposure goes up by twofold. It is also known that drug exposure is increased by a similar amount in CYP2D6 PMs; however, although the SmPC for atomoxetine mentions the effect of CYP2D6 polymorphisms, it does not mandate testing for their presence.
Renal impairment is widely regarded as a risk factor for hypersensitivity to the gout drug allopurinol, with drug package inserts recommending the use of lower doses in patients with renal impairment. By contrast, there is now extensive evidence showing that the presence of the HLA-B*58:01 allele predisposes to serious cutaneous adverse drug reactions to allopurinol, but this has not been implemented in guidelines or as yet in drug package inserts. Prospective studies are quoted as being necessary to demonstrate evidence of clinical utility.
They conclude: “Our arguments here are not meant to suggest that special consideration should be given to genetic tests, but more that the same level of evidence needs to be applied to genetic and non-genetic tests for adoption into guidelines and drug package inserts. Incentives for the development of genetic tests, their pricing and reimbursement arrangements must also be aligned with other health technologies.”
There is actually a Wikipedia entry for the term “genetic exceptionalism” (see here): “Genetic exceptionalism is the belief that genetic information is special and must therefore be treated differently from other types of medical information.” Another link can be found on the website, Genomics Law Report (see here).