DTC genetic tests are a medical device or tool and should be regulated. We have experience with other DTC tests (I mentioned pregnancy testing above) and we have experience with over-the-counter drugs. In all of these cases, a risk-based approach is used to determine how to regulate the product. The question, of course, is how risk is being defined, which goes back to your first question. The risk for DTC genetic tests is in information that could have tremendous significance in choosing a clinical path (for example, information about BRCA1 and BRCA2 mutation status). While I believe that consumers should have direct access to this information if they wish, the information should be provided in context and with background for adequate interpretation of the result. The specific use of a test or test result to guide a medical decision (for example, a mastectomy in the case of the BRCA example) should be initiated by a health professional and be based on results from a validated and appropriately regulated test performed for this purpose. This is not unusual: a second, more rigorous test is often performed before a significant medical intervention is undertaken, hence the DTC genetic test could be viewed as a general screening tool. If the results are intended to be used for a clinical decision, they may have to be verified in a second test that was validated for this specific purpose.
First, we should make health-related genetic tests ‘restricted devices’ available only on order by a health professional. This would eliminate DTC tests, but would allow conventional genetic tests — the ones that currently help patients.
The US Food and Drug Administration (FDA) should then create a process to require proof that specific genetic tests, even when ordered by physicians, are ‘safe and effective’. The statute sets this standard for all medical devices, including diagnostic tests. In the past, the FDA exempted so-called ‘laboratory-developed tests’, but those tests were almost always ordered through doctors. I would not require clinical trials, though that would be within the FDA's power. Instead, I would require proof that each genetic test has both analytical and clinical validity — that it correctly detects the genetic variation of interest and that there is good reason to believe that the genetic variation is associated with a particular health condition. Analytic validity requires both approving the testing method as a medical device and regulating the test site under the Clinical Laboratory Improvement Amendments (CLIA). The FDA could assess clinical validity from the submission of adequate and replicated peer-reviewed findings or from conclusions by professional groups or consensus conferences.
The FDA should then consider whether some DTC genetic tests should be allowed, because, like other over-the-counter devices (such as home pregnancy tests), they can be used safely and effectively without professional help.
All forms of genetic testing — medical or non-medical, traditional or DTC — should be regulated to ensure analytic validity, to maintain appropriate safeguards for sample handling and to avoid exaggerated and false marketing. CLIA should be modernized to consider the special circumstances involved in genetic testing14,15
. The calculation of risk estimates should be transparent and, as suggested in recent discussions of a US National Institutes of Health Genetic Testing Registry, test developers should provide more complete and easily accessible information16
. Genetic tests for traits unrelated to health need not be further regulated.
The question of whether health-care professionals should be required for the ordering and interpretation of genetic tests related to reproductive planning, pharmacogenetics or disease risk is more complex. The safest scenario would seem to require clinician involvement but, since empirical data on benefits and harm are unavailable, such broad regulation might stifle technical innovation and alienate individuals who favour proactive information-seeking, either out of curiosity or in pursuit of health and wellness.
DTC genetic testing has arisen at a historical moment when multiplex testing technologies are becoming affordable but are not yet fully integrated into clinical medicine, and when genetic information is still largely misunderstood as overly deterministic. As the limits and benefits of genetic tests become better understood, we can expect a subset of genetic tests to join other medical tests in being routinely reported by laboratories to clinicians. The clinicians will, in turn, utilize that information in conjunction with the symptoms, family history and physical examination of the individual being tested. At that point, DTC testing may be less relevant. In the meantime, this transitional era demands respect for authentic innovators, in conjunction with judicious collection of empirical data on benefits and harms and, of course, an open mind.
We need a risk-based approach to regulation of genetic tests but there should be some minimum common requirements that all tests must meet. Many of these are set out in the Guiding Principles document developed by the UK Human Genetics Commission (HGC). For instance, laboratory quality assurance should be mandatory, and there should be clear standards regarding the type of information that is provided to consumers.
However, while I have long advocated the use of information-disclosure mechanisms to encourage transparency, I think we need independent control to verify the quality of companies' information in order to ensure that consumers are not being misled. Like the HGC (and both its US counterpart, the Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS) and SACGHS's predecessor body, the Secretary's Advisory Committee on Genetic Testing (SACGT)), I believe that this is most easily achieved through the regulatory frameworks for in vitro diagnostic (IVD) devices. Commercial genetic tests, whether offered DTC or not, should be treated as medical devices and be subject to independent pre-market evaluation to ensure that they meet basic standards for analytical and clinical validity. This latter point is important in terms of fairness — the IVD industry needs a level playing field. It is wrong that, in the United States, companies making test kits have to gain FDA approval, but companies commercializing their products as laboratory-developed tests do not. Industry exploitation of this loophole has grown over time, not least in the consumer genetics space. The FDA has now clearly signalled its intent to address this issue.
However, these basic standards will not always be sufficient; some tests pose greater risks and should be subject to stricter regulation. The question of which tests should be available DTC and which should only be available via a medical consultation is one on which opinions vary widely (not least among consumer genetics companies, many of whom only offer susceptibility or nutrigenetic testing). I believe that pharmacogenetic testing and clinical genetic testing for monogenic disorders and high-risk familial subsets of common diseases (for example, BRCA1 and BRCA2 testing for breast cancer) should only be available via a medical consultation and with appropriate genetic counselling. In many cases, susceptibility testing could be offered DTC, but we need to look carefully at serious or potentially fatal diseases.
Some argue that such an approach is paternalistic and infringes individuals' rights to unfettered access to their genomes. However, the fact is that consumer-genetics companies themselves act as gatekeepers. They control access to our genomic data by setting standards on what they report, how they report it, who they report it to, how much their service costs and through efforts to keep competitors out of the market. We can argue the merits of who is best placed to act as genomic gatekeeper, but let's not pretend that the choice we face is between gatekeepers or unmediated access.
The FDA has considered how to regulate genetic tests since the Human Genome Project began over 30 years ago. At that time, genetic tests were available for approximately one hundred monogenic diseases, such as Tay–Sachs disease and cystic fibrosis. As genomic technologies have advanced, tests are now available for a wider range of multigenic, common diseases.
The FDA is now developing a specific framework to ensure validity for the genetic technologies used in supporting such multigenic genetic testing. In support of the FDA framework, I submit a set of at least five standard practice guidelines for the personal genomics industry, including criteria for performance, service and quality:
- Validity, accuracy and quality. Tests must be run in a CLIA-certified laboratory and in accordance with state and federal regulations. All genetic associations and predispositions must be statistically validated and peer-reviewed.
- Clinical relevance. Information provided to the consumer should be vetted by a team of clinically trained reviewers, with content screened by leading medical institutions.
- Actionability. There must be valid clinical or scientific information available to demonstrate an ability to prevent, delay or enhance treatment options for an included health condition.
- Genetic counselling. Any service that provides genetic testing to individuals must provide access to genetic counsellors to facilitate understanding of the implications of their particular profile.
- Security and privacy. Genetic-testing services must ensure that only the individual member has access to their profile and has complete control over granting access to others. These services must operate in a manner consistent with the Health Insurance Portability and Accountability Act (HIPAA) regulations.