According to Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health, “can individuals now have direct access to certain genetic risk information. But it is important that people understand that genetic risk is just one piece of the bigger puzzle, it does not mean they will or won’t ultimately develop a disease.”
The GHR tests are intended to provide genetic risk information to individuals, but the tests cannot determine a person’s overall risk of developing a disease or condition. In addition to the presence of certain genetic variants, there are many factors that contribute to the development of a health condition, including environmental and lifestyle factors.
The 23andMe GHR tests work by isolating DNA from a saliva sample, which is then tested for more than 500,000 genetic (or allelic) variants. The presence or absence of some of these variants is associated with an increased risk for developing any one of the following 10 diseases or conditions:
- Parkinson’s disease, a nervous system disorder impacting movement;
- Late-onset Alzheimer’s disease, a progressive brain disorder that destroys memory and thinking skills;
- Celiac disease, a disorder resulting in the inability to digest gluten;
- Alpha-1 antitrypsin deficiency, a disorder that raises the risk of lung and liver disease;
- Early-onset primary dystonia, a movement disorder involving involuntary muscle contractions and other uncontrolled movements;
- Factor XI deficiency, a blood clotting disorder;
- Gaucher disease type 1, an organ and tissue disorder;
- Glucose-6-Phosphate Dehydrogenase deficiency, also known as G6PD, a red blood cell condition;
- Hereditary hemochromatosis, an iron overload disorder; and
- Hereditary thrombophilia, a blood clot disorder.
The FDA reviewed data for the 23andMe GHR tests through the de novo premarket review pathway, a regulatory pathway for novel, low-to-moderate-risk devices that are not substantially equivalent to an already legally marketed device. Along with this authorization, the FDA is establishing criteria, called special controls, which clarify the agency’s expectations in assuring the tests’ accuracy, reliability and clinical relevance. These special controls, when met along with general controls, provide reasonable assurance of safety and effectiveness for these and similar GHR tests. In addition, the FDA intends to exempt additional 23andMe GHR tests from the FDA’s premarket review, and GHR tests from other makers may be exempt after submitting their first premarket notification. A proposed exemption of this kind would allow other, similar tests to enter the market as quickly as possible and in the least burdensome way, after a one-time FDA review. According to FDA’s Dr. Shuren, “the special controls describe the testing that 23andMe conducted to demonstrate the performance of these tests and clarify agency expectations for developers of other GHRs. By establishing special controls and eventually, a premarket review exemption, the FDA can provide a streamlined, flexible approach for tests using similar technologies to enter the market while the agency continues to help ensure that they provide accurate and reproducible results.”
Authorization of the 23andMe GHR tests was supported by data from peer-reviewed, scientific literature that demonstrated a link between specific genetic variants and each of the 10 health conditions. The published data originated from studies that compared genetic variants present in people with a specific condition to those without that condition. The FDA also reviewed studies, which demonstrated that 23andMe GHR tests correctly and consistently identified variants associated with the 10 indicated conditions or diseases from a saliva sample.
Unfortunately, from the today’s announcement by FDA, there is no information as to which (genetic) risk factors for any one of the tested ten diseases are being tested with the approved Genetic Health Risk (GHR) tests. Consequently, there is no information as to the scientific and/or clinical, not to forget epidemiological evidence, that the tested genetic risk markers in fact are indicative (i.e., by providing a prospective Odds-ratio, for example) for the tested individual to suffer, some time in the future, from the particular disease under consideration. This would be very important information in order to firstly rate the performance of the tests per se, secondly to give individuals really sound prospectively relevant information to act upon if indicated, and thirdly, to have a feedback and control function by affected individuals, by informed patients, by treating physicians, and of course by regulatory authorities as well. Basically, this would very well fit in with the FDA’s requirement that the results of all DTC tests used for medical purposes be communicated in a way that consumers can understand and use.
The FDA states that from the present and any related future marketing authorisation are exempted any GHR tests that function as diagnostic tests. Diagnostic tests are often used as the (perhaps sole) basis for major treatment decisions, such as a genetic test for BRCA, for which a positive result may lead to prophylactic (preventative) surgical removal of breasts or ovaries. The best example for the measures taken by an affected individual based on a prospective diagnostic test would be the case of Angelique Jolie, who, based on the results of a prognostic and diagnostic genetic test had her breast removed in order to prevent future breast cancer disease.
In real life, however, it will be very difficult to draw the line between diagnostic tests and the newly approved Genetic Health Risk (GHR) tests in that eventually, both types of tests may return information on life-threatening disease risks to individuals who, as a consequence, may take serious measures to seemingly ameliorate or correct such health risks, just as Angelique Jolie did, irrespective of the regulatory classification of the underlying test which delivered the measure-initiating data to the individual (patient). What certainly would not be acceptable, however, even for Genetic Health Risk (GHR) tests seemingly geared towards consumers, would be the notion that risks associated with use of the 23andMe GHR tests could include false positive findings, which can occur when a person receives a result indicating incorrectly that he or she has a certain genetic variant, and false negative findings that can occur when a user receives a result indicating incorrectly that he or she does not have a certain genetic variant. In contrast to an assumption that results obtained from these tests should not be used for diagnosis or for informed treatment decisions, they will be used just in this way, be it by the affected individual, or even treating physicians.
Direct-To-Consumer Theragenomics (DTCT): The combination of all these reflections from above led us to entitle in this short report this newly upcoming area of genetics and medicine and not yet diseased healthy individuals as direct-to-consumer theragenomics (DTCT) in order to embrace the fact that in very many situations simple consumer-geared genetic testing will lead to therapeutic interventions, that is therapies governed by genomic means.