Reply to an article on FDA mission of protecting human health and validation for DTC genetic testing

Reply to an article on FDA mission of protecting human health and validation for DTC genetic testing

Reply Robert article on FDA mission of protecting human health and validation for DTC genetic testing. While the FDA’s mission is to be responsible for protecting human health through ensuring that products like 23andMe are safe and effective, it also supports responsible and timely integration of new innovations for healthcare (“FDA”, 2018).  At issue is whether the genomic data provided by the 23andMe pharmacogenetic testing is accurate, reproducible and could be reasonably understood by the end user. The perspective of the FDA was that there was little in the way of analytical or clinical validation of the pharmacogenetic platform (Annas & Ellias, 2014). This issue has matured since 2013 and 23andMe has now been approved to provide carrier testing results for 36 inherited conditions or diseases.

There are several issues cited in a review by Joanne Kim (2017) which outline both positive and negative aspects of direct-to-consumer genetic testing with the following being the core:

Positive:

1. It is an individual’s right to access their own personal genetic information such that they can make informed decisions about their own health.
2. Genetic testing information enables individuals to modify risk factors and make healthier choices.

Negative:

1. The clinical utility of some of the 23andMe outputs are not clear as there is not necessarily an intervention that can be used to impact the risk factor.
2. Lack of validation may lead to essentially a misdiagnosis and unnecessary treatments.
3. The public does not have the knowledge to appropriately understand the outputs of genetic testing.
4. Lack of privacy with genetic information may lead to genetic discrimination.

The issue of validation is certainly relevant as the results of genetic testing could potentially identify mutations and lead to significant health care decisions an example could be mastectomy and oophorectomy if found positive for BCRA 1/2 gene. In a recent article by Tandy-Conor et al. (2018), the authors reviewed the false-positive rate from several different direct-to-consumer genetic tests and found that 40% of the variants in their analysis were false-positives.  This said, a false-positive, could enable a discussion between a patient and their health care practitioner and then lead to verification though validated Sanger sequencing (gold standard) (Yang et al., 2013).  From a validation perspective at least false-positives lead to more investigation whereas a false-negative might lead to a patient with an actionable mutation not seeking care.

Overall, it is net positive for patients to obtain whole-genome sequencing (WGS). WGS data is being mined and analytics are being used to decipher the similarities between different genomes, link common variants in patients with new mutations and uncover new insights about rare diseases.  A paper by Pinxten & Howard (2014), suggests that even if a treatment is not available, identifying mutations and eliminating disease possibilities allows health care practitioners from “continuing to do tests in vain”.  In this weeks reading, Yang et al. (2013) point out that there is even value in identification of recessive mutations in carriers and understanding mutations that at this point have no disease association.  Perhaps the biggest issues faced with WGS are informed consent, data handling and data privacy and security.  Negative implications could be genetic discrimination and anxiety about gene variants that may never lead to disease.

In conclusion, validation is necessary for DTC genetic testing by comparing outputs to the gold standard, Sanger sequencing. This said, there must be a way to communicate with patients such that they understand the limitations of the data yet can benefit from the cost effectiveness of platforms like 23andMe. Full data validation may not be always necessary, just as some drugs are approved on Phase 1 and 2 data and possibly full validation could occur in parallel versus in a stepwise approach. Ownership of WGS data and the insights captured from WGS data is a concern, but with adequate informed consent and a legal provisions to remove data from the database, WGS by DTC platforms is net positive.

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