Emergence of Hybrid Models of Genetic Testing Beyond Direct-to-Consumer or Traditional Labs

Historically, genetic evaluation was dominated by a clinician-centric model in which a patient’s physician had the central responsibility for testing, such as ordering the test and communicating the results. Conversely, in the direct-to-consumer (DTC) model, consumers are more “empowered” as they can now order their own tests, obtain samples using home test kits, and receive results directly from the laboratory or company that provides the test. The DTC market has expanded substantially recently, reigniting controversies over the potential implications of DTC testing for genetic health risks.¹

However, little attention has been paid to the emergence and effect of new models of genetic testing that fall in a middle ground between the DTC model and the traditional model – the “hybrid lab model” (Table 1). This model is a “hybrid” because it is both consumer-centric and clinician-centric: hybrid labs facilitate easier consumer access but a clinician (who may be the consumer’s regular physician or a physician provided from the lab’s network) orders the test and returns results. This model emerged for a number of reasons. First, there was a perceived need to make testing more consumer-focused and easier to obtain than testing from traditional labs, while also providing “medical-grade” testing so that results can be used for clinical decision-making, in contrast to the DTC model. Second, this approach presented a profit opportunity for labs by generating additional consumer demand via easier access and a network of partnering prescribers, while simultaneously addressing concerns about DTC testing.²

TABLE 1:

Key Distinctions between Direct-To-Consumer (DTC), Hybrid, and Traditional Lab Models for Health-Related Genetic Testing⁽¹⁾

Characteristics	DTC Model(2)	Hybrid Model(3)	Traditional Model(4)
Primary emphasis	Consumer Access & Information - Easier access to testing - Lower cost testing - Out-of-pocket payment - Test results are for consumer information(5)	Consumer Access & Clinical Care - Easier access to testing - Lower cost testing - Out-of-pocket or insurer payment - Test results can be used for clinical decision-making	Clinical Care - Out-of-pocket or insurer payment - Test results can be used for clinical decision-making
Who plays central role in testing steps and interaction with lab	Consumer - Consumer orders test - Lab sends results to consumer	Consumer & Clinician - Consumer may initiate testing but clinician orders test(6) - Lab sends results to clinician and consumer	Clinician - Patient’s clinician orders test - Lab sends results to clinician(7)
Type of genetic testing offered	Limited - Selected genetic health risks and testing methods	Broad - Range of genetic health risks and testing methods	Broad - Range of genetic health risks and testing methods

Footnotes:

⁽¹⁾Models are typologies and not intended to describe specific labs as labs may share characteristics or migrate across models over time. These lab models are for genetic testing for health risks, not ancestry or lifestyle testing.

⁽²⁾The largest DTC model lab is 23andMe.

⁽³⁾Examples of hybrid model labs include Color, Invitae, Natera, and others.

⁽⁴⁾Historically, Quest and LabCorp have been the largest providers of testing using the traditional model. In recent years, labs focusing only on genetic testing emerged, often using a traditional model but also incorporating some elements of the hybrid model (e.g. Myriad Genetics, Ambry Genetics, and GeneDx).

⁽⁵⁾DTC tests are regulated as over-the-counter products and thus results cannot be used for clinical decision-making and diagnosis. Even if health information is included in results, testing must be repeated in a clinical lab setting to be used for clinical purposes.

⁽⁶⁾Either patient’s clinician or lab-provided clinician may order tests and return results

⁽⁷⁾Patients can now also obtain test results directly from the lab as a result of revised regulations.

Hybrid labs are an increasing part of the marketplace with volume and revenues rapidly increasing, e.g., one company reported year-to-year growth in volume and revenue of over 100% from 2017 to 2018.³ Although it is unclear what proportion of labs or testing volume/revenue fall into the three model types, at least 291 labs in the US are performing genetic testing.⁴ One large traditional lab reported having conducted 4 Million tests since its founding in 1991⁵ compared to 3 Million tests by the largest DTC lab since its founding in 2006⁶ and 1.4 Million tests by one hybrid lab since its founding in 2004.⁷

The definition and roles of the hybrid model are poorly understood by consumers, clinicians, researchers, and policymakers. Hybrid models have rarely been examined as a distinct entity and when they have, they are usually labeled and studied as if they were DTC labs even though they are quite different. As a result, there is confusion about the different models and no evidence about their effects and potential benefits and risks. The emergence of the hybrid model has significant implications for everyone involved in genetic testing, providing both potential benefits such as improved access but also potential risks such as lower quality or inappropriate test ordering.

Potential Implications of the Emerging Hybrid Model in the Evolving Genetic Testing Landscape

(1). The hybrid model addresses a gap between the DTC and traditional lab models.

The existence of DTC and traditional lab models - two ends of the spectrum - left a gap in the middle. On the one hand, the DTC lab model addresses a gap in consumer engagement. It challenges the long-standing tenet exemplified by the traditional clinician-centric lab model: that the testing process and decisions must be facilitated by a clinician rather than the consumer. Testing is no longer confined to “patients” who are under the care of their clinician, but is available to “consumers” who are purchasing a “consumer good.” The extraordinary growth of DTC genetic testing, with an estimated 100M genotyped individuals by 2021, suggests that consumers value more active roles in testing. The hybrid model, by facilitating easier consumer access, similarly addresses consumer desires for more engagement and choice in genetic testing.

The hybrid model, however, retains a key aspect of the traditional model: clinicians are still involved in the process as they must order tests and communicate results. The clinician who orders the test can be the patient’s regular physician or when requested many hybrid labs provide access to clinicians via third-party networks. There are no data in the public domain from hybrid labs that clarify what percentage of tests ordered are from the consumer’s regular physician. However, the required clinician involvement enables hybrid labs to be regulated in the same way as traditional labs and thus provide “medical-grade” results. This addresses a gap and key concern about the DTC model, in which results are not certified for use in clinical decision-making.

The hybrid model also addresses another gap: a desire for lower and more transparent prices. It is difficult to compare test prices as they vary by lab, whether self-pay or insurer reimbursement, and whether the lab has a patient payment assistance program. However, in general, prices for genetic testing have declined (with more genes measured for the same or lower price) with DTC and hybrid lab models at the forefront of this trend. Test prices for breast cancer and related cancer risks are a good example. Until a Supreme Court decision in 2013, Myriad Genetics had a monopoly on testing for two key mutations (BRCA½) and charged approximately $4000 for this test. Current list prices are not available but the 2015 list prices for cancer risk panels (including BRCA½ and other genes) from three traditional labs ranged from $3382- $6040.⁸ In contrast, some hybrid labs charge approximately $200 self-pay for a cancer risk panel that includes BRCA½ and other genes.

The hybrid lab model may provide benefits but may also have unintended consequences.

The evolution of DTC testing models or lab models has been described (e.g. McGowan), ² although there are no published studies comparing the three different models to assess their benefits, risks, and effects on patient outcomes. It is not likely that consumers, clinicians, researchers, and policymakers understand the various models of testing and they have different perspectives on their benefits and risks, which may lead to uninformed or inappropriate decision-making and policies. Although stated concerns may reflect general concerns about genetic testing rather than be specific to the hybrid model, the emergence of this model has heightened concerns about issues such as the overuse of testing.

Consumers generally have a limited understanding of genetic testing and personalized medicine. In one survey of 1001 U.S. adults, 66% reported that they have never heard or read anything about personalized or precision medicine.⁹ It is thus likely that consumers do not understand differences in testing approaches across lab models; for example, how cancer risk test results from hybrid labs are different than those provided by DTC labs.¹ It is likely that clinicians’ perceptions of the benefits and risks vary widely, and therefore there is wide variability in whether they order testing from hybrid or traditional labs.

There are other challenges with hybrid labs. Lower self-pay prices may cause insurers to reduce their reimbursement rates, or cause them to perceive genetic testing as an over-the-counter product that does not need coverage. Because low-income consumers may not be able to afford a $200 test, they may be unable to obtain testing if self-payment becomes the norm. Labs at academic medical centers may not be able to match hybrid lab low prices, and the resulting reduced testing volumes could have negative effects on their ability to fulfill their training and public service missions. More laboratories conducting testing may introduce additional variability in the quality and reporting of results, further confusing consumers and physicians. In addition, the emergence of the hybrid model has heightened concerns about the overuse of testing that does not improve health or personal outcomes.

Research and Policy Agenda

The evolving landscape requires evidence so that relevant parties can make informed decisions. The hybrid model cannot be examined as if it was a DTC model, and within the hybrid model, specific labs may have varying characteristics. Consumers need clear explanations of their choices, clinicians need an understanding of the advantages and limitations of various models, and policymakers need information on the trade-offs between costs, benefits, and risks to create informed regulations and policies. The hybrid lab model is likely to become more common and these models portend a future in which the models at the extremes of the continuum - the DTC and traditional lab models – may increasingly morph into hybrid models.

In conclusion, the genetic testing landscape is rapidly changing. It is important for consumers, clinicians, policy-makers, and insurers to understand these changes, and recognize the implications of the hybrid lab model.

Perceived Benefits of Hybrid Model

• Greater access to testing for consumers, particularly when tests are not covered by insurance, when they do not have a regular clinician or choose not to use them to order testing, or when family members of the affected individual should be tested and thus there are additional costs;

• Potentially lower cost for the consumer;

• Greater convenience for consumers when they do not need separate visits for sample collection, genetic counseling, or both;

• Convenience for clinicians who have less paperwork if testing is self-pay and they do not need to request prior authorization or meet other insurer requirements.

Perceived Concerns of Hybrid Model

• Removal of the testing process from in-house or traditional labs may reduce continuity of care;

• Patients may not follow clinician recommendations to purchase tests;

• It can be more difficult for consumers and clinicians to assess lab offerings and quality given the increased choices;

• Guidance and counseling provided by lab-provided prescribers may not be as extensive as warranted, with concerns that required clinician involvement can become more a formality than an informed decision;

• How these prescriber networks work in practice is not well understood, including how they meet varying state requirements for who is licensed to prescribe;

• As with any commercial lab, hybrid labs are profit-motivated.