Genetic tests ordered by doctors race to market, while ‘direct-to-consumer’ tests hinge on FDA approval

WASHINGTON — The Food and Drug Administration is keeping tight watch on “direct-to-consumer” genetic tests but has been taking a hands-off approach with similar tests that have a crucial distinction: a physician’s sign-off.

A physician order appears to be a key regulatory difference between companies like 23andMe, whose tests FDA has said must seek official approval, and companies like Color Genomics, Helix, and Veritas, who are offering some similar tests but don’t need the agency’s permission.

And those companies have made physician involvement as painless as possible — offering to pick the doctor and to solicit the physician’s order after the customer buys the test online. In many cases customers never meet the doctor; in some cases his or her name isn’t provided.

Companies say that the physicians, as well as genetic counselors, diligently review the orders and reject those that are inappropriate. They say it’s a responsible way to balance customers’ desire for health information with some professional oversight. But some outside experts say it’s unclear how meaningful the physician’s involvement is.

“I think a lot of us in the field have wondered about how that’s playing out,” said Dr. Mike Murray, who in April will start working as the director of clinical operations in the Center for Genomic Health at Yale University. “Is it really just somebody donating their professional license in order to order a test, or is it somebody that actually gets involved in figuring out whether a person might benefit from it and following up [about] what they should do with the results?”

Companies say that they are adapting to changing times — and that the FDA should be too. Genetic testing technology is outpacing the current regulatory framework.

Following the model that 23andMe used — submitting individual tests for specific variants in the genome to the FDA for approval — isn’t a sustainable path forward, said Rodrigo Martinez, chief marketing and design officer at Veritas. There are simply too many variants and not enough time.

“The challenge is… if the FDA is going to follow that same approach to [review] tests one variant at a time, it’s going to take us 200 years,” Martinez said. “This does not work.”

In response to questions, 23andMe made no indication that their model would change.

“23andMe’s mission is to enable consumers to access genetic information directly because we believe everyone has the right to access their health information,” said Kathy Hibbs, chief legal and regulatory officer at 23andMe. She said that “we would have no reason to engage in [the] sort of arrangement” that the other companies are using.

Regulatory divide

The fact that a medical professional is involved in ordering genetic tests and providing the results helps move them out of range of FDA regulation, said Dr. Robert Cook-Deegan, a professor at the University of Arizona with a long career of studying genome ethics and the law.

“‘Physician-ordered’ is one of the criteria that FDA is using to decide whether their regulatory authority is triggered,” Cook-Deegan said. “But you’re not going to find that in a statute.”

Rather, based on how the FDA has reacted to 23andMe and to these other companies, Cook-Deegan said, it appears that the physician’s role is important in the agency’s regulatory decisions.

Tests which are marketed to consumers but ordered by physicians are considered to be laboratory developed tests, Cook-Deegan said — a category of products that, for decades, the FDA has chosen not to scrutinize.

“The FDA, rather than choosing to specifically insert itself, has decided that having a licensed medical professional order the test is enough protection for the consumer — patient — whatever you want to refer to that person as — so that [the FDA doesn’t] have to specifically step in,” Murray said.

In this way, the turf wars between genetic testing companies are also part of a larger battle over laboratory-developed tests, which the FDA has chosen not to regulate since it gained the authority to do so in 1976. The agency announced an intention to reconsider that policy in 2010, then reversed course in 2016, and then indicated it might be reversing course yet again late last year.

But genetic tests that consumers can purchase completely on their own — so-called “direct-to-consumer tests” — fall within the agency’s crosshairs. In 2013, the FDA reprimanded 23andMe for selling certain tests directly to consumers without the agency’s permission, and the company took some of its tests off the market. The company has since worked through the process of submitting evidence to FDA to get approval to sell tests for 16 health-related genetic variants as part of its broader ancestry and health package.

Academics say there’s a fine line between the direct-to-consumer model and the hybrid kind now gaining steam.

“The line is unclear at this point in time,” said Dr. Robert Green, a Harvard professor and medical geneticist who is an adviser to Veritas and consults for Helix. “This is an area that is controversial, in the sense that some people feel there should be more interaction with the customer by a physician before a physician orders such a test.”

For some tests offered by Helix, as well as Color Genomics and Veritas, customers may never meet the physician who orders their tests. And for some of the tests available through Helix, customers may never learn that physician’s name.

Martinez said that, while customers who purchase genetic tests using physicians provided by Veritas may never meet that ordering physician in person, the same could be true for patients who get the test through their doctor.

“It sounds like someone might be trying to make the point that having an ordering physician that is not your [primary care physician] is a downside for this, and that’s not the case, because many people have never met their [primary care physician],” Martinez said.

Physician interaction

To start off the process, customers fill out what looks like an online order form, complete with fields for a credit card number to pay for the products. They also upload information about their health.

For all of the tests offered by Color and the Veritas BRCA test, customers can choose whether they want their personal physician to actually order the test, or whether they want to let the company find a physician who can evaluate their health information and, if appropriate, order the test on the customer’s behalf.

The three physician-ordered tests currently offered on Helix don’t give customers the option of using their own physician.

A Color spokesperson said that “there are many independent physicians” who can order the tests on a customer’s behalf, some of whom work for a company called PWNHealth.

“Our mission is, on one hand, to increase access when it’s appropriate, to give people more power, but on the other hand, to do it in a way that protects individuals,” said Bill Paquin, executive vice president of PWNHealth.

Paquin said that every single customer that buys a test is first screened by an algorithm, then evaluated by a genetic counselor, and finally reviewed by a physician.

Liz Kearney, vice president of genetic services at PWNHealth, said that the genetic counselor might reach out to the a consumer if they have a question about the order — and might recommend a different test than the one the consumer ordered.

A Color spokesperson said that the company does provide that physician’s contact information to the customer, and also provides Color-employed genetic counselors “who help you understand the results and can provide additional resources including connecting to expert healthcare providers near your home,” a spokesperson said.

Martinez said that Veritas works with “an organization that has physicians in every state in the U.S.” who are “not employees of Veritas.” He declined to say who the physicians are. He said that customers can get in touch with the ordering physicians if they have questions about the results. Veritas also makes genetic counselors available to customers. If a test finds something that might bode poorly for the customer, then a genetic counselor will reach out to deliver the news, Martinez said.

Admera Health, which offers two physician-ordered tests though Helix, gets ordering physicians and genetic counselors from the company Genome Medical, said Brady Millican, vice president of business development at Admera Health. Admera’s tests look for genetic variants linked to a specific type of diabetes and to a propensity for high cholesterol. (Genome Medical did not respond to a request for comment.)

Millican said that the reports customers receive do not list the name of the physician who actually placed the order for that customer’s test.

“We tell them to go back to [their own] physician,” Millican said.

The distance of the physician who orders the test raises questions for some bioethicists.

“The really important ethical issue is, this information is not of very much use to anyone if they get it outside of the context of routine medical care,” said Barbara Koenig, a professor in the University of California San Francisco School of Nursing who direct’s the university’s bioethics program. “You can’t take any of the actions that are required if you find that you are at heightened risk, essentially, by yourself.”

Companies are still forging ahead. Justin Kao, co-founder and senior vice president of business development and partnerships for Helix said that they will be offering new tests to look for genetic variants associated with cancer, cardiovascular disease, and drug effectiveness — all of which will be signed off on by physicians in a similar way to the current tests.

Martinez, of Veritas, said that his company is looking forward to a day when they will be able to offer more products, such as whole-genome sequencing, directly to consumers, with no physician involved in the ordering process — provided that the company is responsible in the way that it provides the data to patients.

“What we would like is for consumers to be able to order their whole genome sequence without a requirement of a signature from a physician, as long as the way that you are returning the results on the back end is done properly,” Martinez said. “What does that mean? Any pathogenic variant has to be communicated through a professional.”

The company is currently preparing to have “initial conversations with the FDA,” said Birgit Funke, vice president of clinical affairs, “to seek advice on the path towards regulatory approval of whole genome [sequencing, interpretation, and reporting].”