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DTC Genomics Firms Say They Want to Comply with FDA Regs but Maintain Direct Access

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By Turna Ray

This article was originally posted March 11.

Direct-to-consumer genomics firms may have agreed to come under compliance with the US Food and Drug Administration's medical device regulations, but they are not ready to give up the direct access business model.

At an advisory committee meeting held last week to discuss how FDA should regulate DTC genomics firms, several companies said that they are willing to meet the agency's clinical and analytical validity requirements, but will push to maintain direct-to-consumer marketing for their products.

The FDA convened the Medical Devices Advisory Committee's Molecular and Clinical Genetics Panel for two days last week to get input from experts about the circumstances under which firms like 23andMe, Decode Genetics, Navigenics, and Pathway Genomics can continue to sell their genomic testing and interpretation services to consumers, and when a physician needs to be involved.

On the first day of the meeting, the advisory committee held that consumers should get a prescription from a doctor before purchasing genetic tests that could potentially be used to inform healthcare decisions. The panel was more comfortable with maintaining direct consumer access to certain nutrigenetic tests, but felt that carrier testing, genetic testing to gauge people's predisposition or susceptibility for diseases, and pharmacogenetic testing should be routed through a physician (PGx Reporter 03/09/11).

On the second day of the meeting, the FDA asked the committee to consider — on a hypothetical level — what types of labeling, risk disclaimers, and clinical and analytical validity requirements would be required if the agency were to allow DTC marketing of genetic tests.

It was clear from the discussions that the FDA is still working through its regulatory stance with regard to DTC genomic testing. The agency did not reveal too much at the meeting other than its determination that genome scans sold by DTC firms are medical devices, something the FDA stated in letters to several DTC genomics firms last summer (PGx Reporter 05/26/10).

Protecting Rights and Interests

The advisory committee's recommendation against direct access for clinical genetic tests reignited accusations that the FDA is trying to play gatekeeper between the public and their genomic information.

"23andMe has been proactively collaborating with the FDA for more than a year, and we believe we have a clear path to pursue and obtain FDA approval of our entire genetic testing platform, though the process will take time to complete," said general counsel Ashley Gould during the meeting.

However, after the meeting, Gould told PGx Reporter that the company's position on DTC marketing of its services remains unchanged. "We believe consumers have a fundamental right to directly access their own genetic data and that all genetic testing services should be held to the same standards," she said.

At the meeting, 23andMe proposed that the agency adopt regulations for DTC genomics firms that are flexible and do not restrict technological innovation; convene a cross-sector working group to define clinical validity specific to genetic testing; and establish requirements that apply to all genetic testing services, both in the DTC and clinical settings.

Pathway, which is currently providing its service through doctors, told PGx Reporter that information from genetic tests can be used by consumers in many different ways other than making personal healthcare decisions.

"Pathway Genomics believes that people have a right to their own health information, and that doing so can improve the health and wellness of individuals while also helping to lower the total costs of healthcare," the company said in a statement, adding that a mandatory genetic testing registry could allow consumers to be aware of the benefits and risks of available tests. The NIH is currently developing a voluntary genetic testing registry.

Jeff Gulcher, chief scientific officer at Decode Genetics, noted that while the company agreed with the FDA that DTC genetic tests should meet the agency's criteria for clinical and analytical validity, these criteria should not be different from those for physician-offered genetic tests.

"Kari Stefansson, our CEO, has publicly stated several times over the last years that the FDA should indeed ensure safety and effectiveness of DTC tests beyond the CLIA and CAP accreditation we already have," Gulcher said. "We have not been pressured by the FDA to shut down our DTC services, and Decode will continue to work closely with the FDA to clear our DTC offering, even though the majority of our tests are already ordered through physicians."

Navigenics, another company that has moved away from the DTC model and is providing its service through doctor groups and corporate wellness programs, did not present at the meeting but had company representatives in attendance.

"We have the highest regard for officials at the Office of In Vitro Diagnsotics, and welcome a vigorous discussion on the role and future of genetic testing," Amy DuRoss, Navigenics' VP of Policy and Business Affairs, told PGx Reporter. "However, we don't believe this two-day meeting has added much meaningful new information to the FDA’s deliberations on the best regulatory pathway for clinically guided personal genetic services like ours, or for direct-to-consumer genetic tests.

"Unfortunately, much of the discussion among the panel participants at the meeting fell below the sophistication and superior understanding of the testing platforms, state of scientific discovery, and clinical potential for our subset of genetic testing demonstrated by the FDA officials we have engaged with over the past five years," DuRoss said.

Complex Issues

The primary argument for supporters of direct-access testing is that a prescription requirement for clinical genetic tests is an affront to people's right to their own genomic information, but the FDA is considering a range of issues that are much more complex than many proponents publicly acknowledge.

For example, it is worth noting that the agency hasn't take steps to regulate Illumina's whole-genome sequencing service, which provides consumers with their raw genomic data. Illumina requires a prescription for this service and does not provide any clinical interpretation of the data.

The FDA has so far only taken regulatory action against companies that are interpreting genomic data using proprietary algorithms and testing platforms.

Furthermore, the cost of these services is also a barrier to access and, as such, may skew current assessments that access to genomic data poses little harm to public health. Committee members pointed out that it is hard to gauge how genomic data will impact the general public, since most of the available behavioral studies have been conducted in small cohorts of highly educated and wealthy individuals who have been followed for a few months, such as a recent study published in the New England Journal of Medicine by researchers at the Scripps Translational Research Institute (PGx Reporter 1/12/2011).

Additionally, DTC genomics companies rarely acknowledge their economic motivation to combat regulatory barriers that would restrict the way they can market their products.

For example, Tiffany House, a patient representative on the panel from the International Pompe Association, put forth the recommendation that perhaps direct access to genetic testing can be maintained if these companies require consumers to pass a quiz on basic genomics topics before allowing them to purchase a test online.

In order to participate in George Church's Personal Genome Project, for example, study participants must pass an extensive eligibility screening process, learn about genomics and the study, and take a test to ensure they understand the basic science and the risks of taking part in the research. Only after people pass this screening process will the PGP sequence study participants at no cost.

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Despite the fact that such an educational model already exists, none of the for-profit genomic testing services have championed such a strategy for their customers. Although customers of DTC testing services have access to educational materials and genetic counseling, none of the companies ensure that customers understand the risks and limitations of genetic testing before getting tested. Under the "take charge of your own health" philosophy, it's left up to the consumer to understand the terms of these services and the scientific data explaining how the companies calculate risk. It's debatable whether much of this data is presented in a way that the general public can understand.

Mary Pendergast, a lawyer and director of ARCA Biopharma, asserted during the meeting's public comment period that the advisory committee members were pandering to doctors because they themselves were physicians and could gain financially by recommending that genetic tests get funneled through them. To this, panelist Majid Moridani of Texas Tech University Health Sciences Center countered that while many committee members were MDs, among them were also researchers who were not practicing physicians.

Committee member David Ransohoff of Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill, acknowledged that doctors can be paternalistic, but noted that's part of the job description. "I know people who are on gluten-free diets, and I may not agree that they should be. Is it none of my business as a [medical] professional, or do I have a role?"

Decode's Gulcher, on the other hand, sympathized with physicians, while maintaining that it should be up to the individual to decide when to seek medical advice. "Stefansson and I are both physicians and can understand the point of view of the physicians and the epidemiologists on the committee to be cautious and to have physicians control access to genetic risk tests," he said. "However, we believe that genetic information on disease risk should be directly accessible to patients if they wish to learn it.

"Today's medical community encourages individuals to take personal responsibility for their health by providing direct access to websites to calculate their personal risk for diseases like heart attack and breast cancer without a physician," he continued. "DTC genetic testing takes that to the next level."

Over-the-Counter Access?

FDA's current medical device regulations do allow for certain types of products to be marketed to consumers with limited involvement from a doctor. For example, home-use tests, such as those for glucose monitoring, pregnancy, and alcohol breath testing, can be purchased without a prescription and let the consumer perform the test and interpret the results.

Then, there are over-the-counter tests, such as collection kits for HIV, HbA1c, and hepatitis C, that allow the consumer to collect a biological sample on their own at home. However, the interpretation of that sample is done by a lab and the results are reported to the consumer over the phone through a counselor.

The FDA highlighted that home use tests are rigorously manufactured to ensure that they are simple to use, have a very low error rate, and are not affected by different operators or environmental conditions. In many ways, over-the-counter tests are "much tighter" in terms of their specifications and ability to perform accurately and consistently than are prescription-based tests, said Elizabeth Mansfield, director for personalized medicine at the OIVD in FDA's Center for Devices and Radiological Health.

When Pathway attempted to sell saliva-collection kits for its genetic testing service through Walgreens and CVS stores, the agency informed the company that it considered the collection kits to be medical devices (PGx Reporter 05/19/10).

While comments from agency officials this week made it clear that FDA still believes sample-collection kits to be medical devices under its regulatory purview, it appears that one option the FDA might consider is to maintain direct consumer access to such kits while still requiring that a genetic counselor or a doctor interpret consumers' genomic data.

During the meeting, the FDA pointed out important differences between currently available OTC tests and genetic tests that provide information about disease risk and drug response.

For example, pregnancy tests are usually taken by women who want to make decisions about family planning, but they have to see a doctor eventually if they want to make such decisions. Similarly, home glucose meters allow diabetes patients to monitor their disease, but these tests are not meant to diagnose disease. And finally, OTC drug detection tests are not definitive and require confirmation through a doctor or lab.

Compared to the above home use tests, which have been on the market for some time, genetic tests that provide disease predisposition and drug response risk assessments are still based on an evolving science. Even though much of the currently available gene-disease information is of questionable clinical utility, the advisory committee pointed out that patients can learn from these tests that they are carriers for genes that confer a high risk for serious diseases, such as BRCA mutations that are linked to increased risk for hereditary breast and ovarian cancer.

In order to ensure that people understand the information they get from genomics firms, committee members said that at the minimum — even if tests are sold through a DTC model — consumers should receive this data from someone certified to assess genetic information, such as a genetic counselor or specialist. Most DTC genomics firms offer genetic counseling services over the telephone and online, but these services are optional.

Mitigating Risks

The advisory committee, having stated on the first day of the meeting that genetic testing companies should not be allowed to market clinical tests directly to consumers, struggled during the second day to consider scenarios in which genetic tests might be available under a hypothetical direct-access model. In the end, the committee recommended that in order to allow DTC genetic testing, these products must be labeled in a way that describes their limitations and risks in language that can be understood by the lay person.

"The limitations of the test should be listed as vigorously as the benefits in the label," said Margaret Davis of Morgan State University and a consumer representative on the panel.

Other committee members pointed out that most DTC genomic tests only have clinical validation data on European populations. As such, FDA would not be able to maintain direct consumer access for a genetic test and enforce that that test is only being used by people of European ancestry. To mitigate this risk, the FDA should present in labeling the specific information the test can and cannot provide to the consumer, committee members said.

The advisory committee also held a lengthy discussion about how the risks of these tests should be calculated and presented to consumers to avoid misinterpretation. There was debate between panelists as to whether relative risk and odds ratio calculations are the most accurate way to present genetic risk data. Many committee members felt that DTC companies' risk calculation methods did not provide the most accurate picture of risk to consumers, and that DTC firms can do more to present this information in a way that is easier for consumers and doctors to understand.

The agency also asked the committee to consider the best method of ensuring the analytical validity of genomic scans that query a multitude of SNPs. "One suggested approach (i.e. for cytogenetic arrays that query the entire genome) is to select and validate an appropriate subset of genetic markers, with an inference that the platform as a whole is analytically valid," FDA said in background documents for the meeting. "Another approach is to explicitly validate each marker that is used in generating a test result."

Committee members favored the first option. "You'll never get anything going if you have too much to look at," said panelist Ralph D'Agostino of the Comprehensive Cancer Center at Wake Forest University, who was also the co-principal investigator of the Framingham Heart Study.


Have topics you'd like to see covered in Pharmacogenomics Reporter? Contact the editor at tray [at] genomeweb [.] com.

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