Regulating genetic tests: lessons from 23andMe

By Mark Kroese

9 December 2013


The regulation of genetic tests has received renewed attention thanks to the recent move by US regulator the FDA to halt marketing of company 23andMe’s Personal Genome Service and the company’s subsequent cessation of health-related information provision to new customers (see 23andMe). There is undoubtedly a need for regulation of direct-to-consumer genetic tests, and it seems clear that 23andMe failed to comply with the FDA’s demands. But what should regulators’ requirements be? 

Clinical utility is not an issue. Whilst it is a matter of great interest to the individual, and to healthcare funders - whether public, commercial insurance providers, or individual purchasers - it is not generally within the regulatory remit to examine utililty, which is often subjective and varies between individuals. What regulators of genetic tests with any potential medical applications want to know about (including the FDA is evaluating 23andMe’s tests) are analytical validity and clinical validity.  

Analytical validity is relatively straightforward, showing whether a test accurately detects and distinguishes its intended targets, in this case genetic variants. Clinical validity is a more complicated issue, comprising two distinct elements:

1.    Scientific validity

Is there plausible scientific evidence to link a given genotype and a specific phenotype, such as an increased or decreased risk of a certain disease?

2.    Test performance

How reliable is the predictive value of a test, based on evidence in the real world?

To market a test that makes claims of clinical validity necessitates evidence of scientific validity; it would otherwise be a fraudulent claim. However, assessing scientific validity for genetic tests can be difficult as there are no agreed evidence standards, a problem is exacerbated by the rapidly increasing complexity of genomic tests.

The performance of a test should be demonstrated in its intended population; for most genetic tests this is a defined sub-population (eg. colorectal cancer patients in whom the presence of a familial mutation is suspected), but in the case of 23andMe’s offering it is the general population. Whether or not it is reasonable for a regulator to impose the equivalent of Phase III trials to generate evidence of test performance on a provider is open to debate.   

In the context of consumer diagnostics where there are no physical safety issues posed by the testing process itself, there are two questions to be answered. First, should the regulator allow only tests with proven clinical validity (i.e. those which are both scientifically sound and make clinically accurate predictions) to be marketed, or would evidence of scientific validity suffice? Second, might adequate protection be provided to the consumer (assuming adequate analytical validity) provided that the clinical evidence, either positive or negative, be placed in the public domain so that the consumer may access tests even without evidence of clinical validity, provided that he or she is in full knowledge of that lack of evidence?

It may seem wholly inappropriate for a regulator to permit the sale of an essentially useless test as a medical or health related product, but if there is to be consistency in these matters then sales of products such as homeopathic remedies should certainly not be permitted either, whereas the US FDA and UK MHRA both license homeopathic products without evidence of efficacy. Similarly, why don’t we impose regulatory regimes on weighing scales? It can be argued that knowing one’s weight may currently have a greater predictive value for future heart disease than a test from 23andMe. 

23andMe’s failed attempts to gain exemption for their PGS from the FDA statutory standard of being able to demonstrate clinically significant results are perhaps less outrageous if compared with homeopathic treatments rather than other clinical predictive tests. The issue is less with the regulation of genetic tests per se as with the regulatory systems themselves and our expectations of them.

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