As the direct-to-consumer (DTC) sector of the laboratory industry has exploded, advocates have asserted that these tests remove potential barriers in our traditional healthcare system and increase access to important health information while boosting both convenience and privacy.

Consumers now have access to a wide range of tests without a physician’s order, including sexually transmitted infection and allergy screening, and assessments of cholesterol, vitamin D, and nutritional deficiencies.

DTC genetic testing has received the greatest share of attention in popular media and may be the most appealing to average consumers. Available testing ranges from identifying individuals’ ancestry and familial relationships to elucidating certain genetic traits along with wellness and genetic disease risk factors.

Some genetic testing results may be benign—“likely to dislike cilantro.” However, many DTC tests report variants for which little evidence exists to support association with a trait or health condition, such as a DCDC2 gene polymorphism and reading ability.

At the other end of the spectrum DTC testing for conditions with strong evidence to support phenotype-genotype relationship and evidence-based guidelines also raises concerns. In the case of BRCA1- and BRCA2-related cancers, these tests may change medical management and have resulted in de facto population-based screening.

Some DTC laboratories provide consumers with raw data files of genomic variant information that has not been validated or subjected to quality protocols. While the laboratories will often include a disclaimer that the data is for informational purposes only, consumers increasingly are sharing this raw data with third-party online interpretation tools.

Some studies have found that around half of the results provided through these raw data interpretation services are inaccurate, in which a positive result is not confirmed through clinical testing (1). Similar problems may exist in other areas of DTC testing.

Unfortunately, it is becoming increasingly difficult to distinguish DTC tests from those ordered in clinical settings. All types of DTC test offerings have grown rapidly in recent years both through startup ventures as well as major laboratories entering the DTC business.

DTC test services also vary in how they’re marketed: Some companies enable consumers to order on their own without a physician while others use contracted physicians who will never provide direct care for a patient.

Guidance from regulatory bodies provides little clarity.

For instance, the Food and Drug Administration (FDA)-approved 23andMe Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants) includes labeling that recommends “…prior to making any medical decisions, confirmatory clinical testing should be performed.”

However, 23andMe operates a CLIA-certified laboratory, so it is not clear what differentiates clinical testing in this context, aside from being ordered by a physician.

Some have argued that at-home collection kits used by DTC companies do not adhere to chain-of-custody requirements that are upheld in clinical testing environments to ensure that results belong to the listed individual. However, many traditional clinical laboratories, particularly in the genetic testing realm, also provide at-home buccal or saliva collection kits which don’t require identity confirmation.

Although CLIA certification, accreditation by the College of American Pathologists (CAP) or other entity, as well as FDA approval and ISO certification are important benchmarks, gaps remain in our current system that put quality and patient safety at risk.

Implications for Healthcare Providers

Clinicians face the challenge of navigating alongside their patients the shifting landscape of DTC testing, especially when DTC test reports yield unanticipated and sometimes anxiety-provoking findings. Indeed, healthcare providers may feel stuck sorting out a mess they had no part in creating.

Clinicians also need to determine when and how to incorporate test results into medical management decisions for their patients.

Similarly, they need to decide when, if ever, a DTC test report should be included in a patient’s medical record if the DTC company does not have solid specimen collection and chain-of-custody procedures. Providers also discern when it is appropriate to repeat a test to clinically confirm or refute a DTC test result.

Clinicians without specialized training are left deciding which clinical laboratory to send follow-up testing to, sometimes relying on their experience in other areas of testing or the laboratory’s reputation.

Given that CLIA certification and CAP accreditation are not always sufficient differentiators, they would benefit from trusted colleagues in clinical genetics or laboratory medicine to provide guidance under a laboratory stewardship program.

The Impact on the Healthcare System

Time will tell how DTC testing will shape healthcare policy. Societal and individual costs for healthcare are at an all-time high, and both policymakers and providers wish to move away from disease management toward preventive healthcare. This environment makes the availability of low-cost and easily accessible health information enticing. But for consumers who are anxious and confused about their reports, or whose results suggest a real medical problem, the path forward may be costly.

Clinicians presented with DTC results may feel compelled by ethical or medicolegal considerations to offer confirmatory studies and subsequent medical follow-up, but there are concerns about who should pay, particularly in asymptomatic patients without clear medical indications for such interventions. Many observers have celebrated recent announcements that some insurers may pay to have DTC testing confirmed through a clinical laboratory.

However, it remains unclear and warrants investigation as to whether a DTC testing approach truly meets the goal of engaging patients in their own health and wellness, thereby improving health outcomes and decreasing the cost of healthcare across the population.

Given the popularity and growth of consumer-driven medical testing, the time is now for the field of laboratory medicine to act on these ethical problems and regulatory gaps. We need to clarify the quality standards of DTC labs and to increase transparency so that consumers, healthcare providers, and insurers alike all will better understand these differences.

Continued line-blurring between DTC and clinical testing risks undermining the value and legitimacy of the entire field of laboratory medicine at a time when the promise of diagnostics to improve health is greater than ever.

References

  1. Tandy-Connor S, Guiltinan J, Krempely K, et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med 2018;20:1515-21.

Jacquelyn Riley, MS, LGC, is a genetic counselor in the molecular pathology lab at Cleveland Clinic in Ohio and participates in the organization’s laboratory stewardship committee to pro-mote best practices for use of genetic testing. Email: RileyJ2@ccf.org

Katie Stoll, MS, CGC, is a genetic counselor and executive director of Genetic Support Foundation in Olympia, Washington. Email: kstoll@geneticsupport.org 

Epilogue: An Average Kid

By Katie Stoll, MS, CGC

Many medical organizations agree that patients and providers should exercise extra caution when considering genetic testing on children. In most cases, guidelines recommend that genetic testing only be performed when the results would affect current medical management and otherwise should be deferred to preserve a child’s autonomy and privacy.

I ordered a childhood direct-to-consumer (DTC) test to see firsthand as a trained genetic counselor what information the testing company included for caregivers who might be considering having their children’s DNA tested with the promise to “know your child even better” and receive information about their fitness and language abilities. The glossy DTC kit contained a swab and postcard requesting only a name, phone number, and email address. There was no further information about or consent for the test.

I decided to swab the cheek of our family dog, Ginger. As Ginger doesn’t have the best oral hygiene, the swab looked as though I had run it through a pile of dirt. To my surprise the CLIA-certified lab that processed the specimen did not flag Ginger’s sample as out of the ordinary. I received an email with a link to her test report a few weeks later. Ginger’s results suggested that she was an average kid.

I considered the possibility that a canine sample could have produced at least some of the polymorphisms the laboratory used in its panel. So, I sent in a blank specimen, only running the swab under the tap water of my kitchen sink. The tap water analysis varied slightly from Ginger’s result, but again the lab found nothing amiss. It was disheartening that the report was signed out by a laboratory director who is a geneticist with a doctorate. While both my dog and tap water might be average, it’s clear that this DTC lab offers below average performance.


CLN's Laboratory Stewardship Focus is supported by Seattle Children's Patient-Centered Laboratory Utilization Guidance Services

Seattle Children's Patient-Centered Laboratory Utilization Guidance Services