Lentis/Direct-to-Consumer Personal Genomics

=Introduction to Personal Genomics= Since predictable inheritance patterns were first described, there have been increasing efforts to describe the biological basis for who and what humans are. These efforts eventually led to the Human Genome Project (HGP), a government-funded project to sequence the entirety of the human genome. The cost of this project was $3 billion, but the current cost to sequence a genome has dropped to approximately $1,000 as of 2014. The increasing cost-effectiveness of the technology has revealed much information, and rapidly accelerated the field of genomics, especially with regard to human applications.

Genomics is now defined as “the study of all of a person's genes (the genome), including interactions of those genes with each other and with the person's environment.” Initially applied with regard to the HGP and its whole-genome sequencing efforts, it has come to be associated with the study of the key differences between individuals. In personal genomics, these genetic differences are often indicated by single-nucleotide polymorphisms, or SNPs, which are DNA sequence variations affecting less than 1% of the population. These are the markers used to identify disease risk and other health traits. Personal genomics companies use already-known sequences to create devices which search for certain SNPs in an individual’s genetic sample. The companies, including 23AndMe, Pathway Genomics, and more, then report (and often offer interpretations of) the presence or absence of certain SNPs. This kind of direct-to-consumer presentation of genetic information represents a challenge to the traditional medical model, and encapsulates several complicated issues with regard to communication, interpretation, and ownership.

=Ambiguity of Genetics Testing Results= Genomic testing approaches but remains distinct from the field of medicine. The techniques used are scientifically based, but unlike a medical diagnosis, the results of a genetic test are not conclusive, often only indicate predispositions, and may not have a clinical impact. The combination of their inherent uncertainty with varied standards of interpretation that exist today, can have a significant impact on consumers' understanding. Finally, there is a distinction that must be made between genomics testing's role in medicine versus its role in the overall health industry.

Inherent Uncertainty of Sequencing
One particular difficulty which arises when interpreting genomics testing results is the fact that SNP-based genetic screening is inherently uncertain. Only 1/300 of genetic information can be obtained by analyzing SNPs, and the majority of that is entirely unrelated to health (or unknown at this time). SNPedia, a wiki-style website designed to help customers interpret their personal genomics data, admits that “We are just beginning to learn which of the 30 million or so possible polymorphisms influence health, either individually or in sets. Many polymorphisms are likely to have either no effect at all, or to have such subtle effects that it will be many years before their consequences are understood.”

Lack of Standards for Interpretation
Genomics testing companies offer varying consumer services that rely on similar scientific principles, but have varying standards for what is presented to consumers. In an example from 2013, a 28-year-old woman named Kira Peikoff purchased genomic testing services from Genetics Testing Laboratories (G.T.L.) and 23andMe, two leading personal genomics companies. 23andMe told her that she had a “medium” risk for developing heart disease at 10.3%, while G.T.L. said her risk was “decreased” at 15.7%. In the same tests, Peikoff’s highest risks according to 23andMe were psoriasis and rheumatoid arthritis, each double her expected risk at 20.2% and 8.2% respectively. G.T.L. rated these diseases as her lowest risks, at 2% and 2.6% respectively.

Effect on Consumers
Consumers can face difficulty in making use of genetic testing when the numerical and interpreted results are varied from company to company. Consumers' uncertainty in these results could lead to analysis paralysis, where no action is taken. Even worse, consumers could make harmful medical decisions based on genetics testing results. According to Hank Greely, professor at Stanford Law School:

"“When a woman's analysis shows that she has at low risk for breast cancer, Greely said, she could be inclined to think, 'Thank God I no longer have to take those damn mammograms.' But that’s not an accurate read of the data because having a lower than average risk doesn’t mean a person’s risk isn’t significant.”"

Personal genetics testing can also be beneficial. Consumers who discover that they are predisposed to an illness may make positive lifestyle changes based on diet, fitness, or other factors in order to prevent the disease or mitigate its impact. With healthcare costs in the US at $2.9 trillion, preventative genetic testing could have significant financial benefits on a macro scale, in addition to individual health benefits.

Health vs. Medicine
Almost universally, personal genomics companies market their products while avoiding the use of specifically medical terms. For example, 23andMe marketed their services as “personal insight into ancestry, genealogy, and inherited traits,” at one point launching a marketing campaign to “Know more about your health!” This kind of language implies medical relevance without explicitly stating it. In reality, 23andMe's terms of service specifically state that they do not provide medical advice, and disallow the use of their information in a medical context, despite their apparently contradicting marketing. Similarly, Pathway Genomics markets its BRCATrue breast cancer risk test as “clinically actionable” rather than medically significant, and other companies follow related patterns. When expectations and reality are so divergent, consumers may face further challenges in knowing exactly how to use the product and its information.

=FDA Regulation= Regulation by the Food and Drug Administration (FDA) of personal genome services has been unresolved for years, and no formal legislation is yet available to companies. When the FDA Commissioner announced plans for increased regulation of laboratory-developed tests (such as those used in personal genomics), the American Clinical Laboratory Association (ACLA) responded with fierce opposition, issuing a citizen petition.

Personal genomics services have disrupted the FDA’s existing regulatory framework, as there is insufficient data on their accuracy to make a decision. In regulating personal genome services, the FDA bases its policy on the potential harm caused by inaccurate interpretations of personal genome data.

Pathway Genomics
Pathway Genomics announced in 2010 that it would sell personal genetic test kits at the nationwide drug store chain Walgreens. The tests would analyze saliva samples to assess a customer's risks for over 70 diseases including hypertension and lung cancer. Walgreens has since suspended these plans due to regulatory pressure. The FDA published a letter arguing that because Pathway's test provides results that can modify a consumer’s life and health regimen, it meets the definition of a medical device as defined in section 201(h) of the Federal Food Drug and Cosmetic Act. The FDA would require documentation of regulatory clearance for this personal genome product before allowing its sale.

23andMe
The FDA took a firm position to regulate personal genome services in its regulation of 23andMe, which became a well-publicized controversy in recent years. Founded in 2006, 23andMe is a company that aims to “connect you to the 23 paired volumes of your own genetic blueprint... bringing you personal insight into ancestry, genealogy, and inherited traits.” The company offered a flagship DNA kit for $99, with instructions on how the customer should provide a saliva sample and send the kit back for genomic sequencing. The results can explain things about one's traits using certain SNPs, including disease risks. The issue of offering medical information has led to a battle between 23andMe and the FDA. The FDA issued a first “cease-and-desist” letter in 2010, and 23andMe began to seek 510(k) premarket notification clearance in 2012. The FDA referenced extensive communication with 23andMe, in which it requested specific feedback on study protocols that would prove 23andMe’s tests were useful as diagnostics and other tests to prove the 23andMe kits gave consistent results, but received inadequate response from 23AndMe. The FDA ordered the company to discontinue marketing on November 22, 2013. “Serious concerns are raised if test results are not adequately understood by patients or if incorrect test results are reported,” the FDA wrote in its letter to the company. Since receiving the letter, 23andMe continues to offer DNA testing services, but no longer interprets the results to consumers.

Critics of regulation
In the ACLA's petition against the FDA's planned increase in regulation of laboratory-developed tests, they argued that additional regulation will stifle the industry. Others cite freedom of speech and the right to commercial speech. Some consumers vie for this right to know information about their health, whether it is beneficial or harmful. After the FDA crackdown of 23andMe, consumers have sought alternative outlets to interpret their genetic testing information. Some have used services such as Promethease, which retrieves interpretation of DNA information based on scientific literature. “Don’t let the man stop you,” said one Promothease user.

=Ethical Issues= Because the results of a genetic test are not conclusive, they were not initially regulated in the same way as medical diagnoses even though it has significant impact on the patient's liability, safety and privacy. Legislation in this area has resolved this to some degree, but there are still issues unique to genetics testing that present significant liability and privacy risks.

Genetic testing results are not covered by default under legislation protecting patient rights and privacy. The Affordable Care Act protects against discrimination based on genetic diseases, but not a genetic predisposition to a disease. There is already legal precedent for patients to sue genetic information providers for negligence in providing results. The converse to this is liability for over-provision of information. If a patient acted on genetic testing results by making lifestyle or health decisions that ultimately harmed them, they could attempt to sue the provider for damages. There is no legal precedent for or against this situation.

Individual privacy is a major concern for genetic testing. An individual’s genetic profile is relevant to some degree to all those who have a stake in that person’s future, such as their family, employer, and health insurance provider. Furthermore, an individual’s genetic testing results have direct implications for family members, who share their genetic information and may have similar health risks. Genetics testing has inherent barriers to privacy, as identifying information can be recovered from personal genomes using a publicly-available genealogy database. Anyone with the capability to analyze information from these databases can piece together a reasonable approximation of one's genetic testing results based simply on their surname.

Related Legislation
Genetic testing is a rapidly developing science, and legislation in the field struggles to keep pace with current techniques. .

In 2008, Congress passed the Genetic Information Nondiscrimination Act (GINA). This took steps to extend consumer protection based on medical diagnoses to the realm of genetic testing. Health insurance companies can no longer use genetic testing results to discriminate against individuals in terms of coverage or pricing, and employers cannot use it to influence hiring practice or salaries. However, the act does not cover life or disability insurance. Genetic testing focuses on long-term impacts and actuarial health risks, so this is a major area where genetic testing may affect consumers’ options.

=Conclusion= The relationship of personal genomics to healthcare has yet to be fully defined. Despite the benefits of having genetic information, there is inherent uncertainty in the results and the interpretation of such data. This cost-benefit calculus needs to be considered by consumers, businesses, and federal agencies as they grapple with how personal genomics technology ought to be used in healthcare.

=References=