Evaluating Web-Based Direct-to-Consumer Genetic Tests for Cancer Susceptibility

Abstract

PURPOSE

Recent years have seen direct-to-consumer (DTC) genetic testing for cancer susceptibility change dramatically. For one, a new model now dominates the market where tests are advertised to consumers but ordered by physicians. For another, many of today’s tests are distinguished from earlier DTC offerings for cancer susceptibility by their scope and potential clinical significance. This review provides a comprehensive overview of available DTC genetic tests for cancer susceptibility and identifies aspects of the DTC testing process that could affect consumers’ ability to make informed decisions about testing and understand their results.

METHODS

First, we provide an overview of each DTC genetic test for cancer susceptibility that includes information about cost; who orders it; whether variants of uncertain significance are returned; availability of genetic counseling; intended users; management of variant reclassifications; whether it is characterized as diagnostic, actionable, and clinically valid; molecular technique used; and Clinical Laboratory Improvement Amendments/College of American Pathologists status. Second, we identify six aspects of the testing process that could affect consumers’ ability to make informed decisions about testing and interpret their results: How companies use certain terms (eg, medical grade or clinical grade); how companies use consumers’ health information during the ordering process; the extent of genetic counseling provided by companies; companies’ procedures for returning results; the role of company-provided ordering physicians; and companies’ procedures for communicating variant reclassifications.

RESULTS

On the basis of our review of companies’ Web sites, we believe that consumers would benefit from more information about these aspects of testing.

CONCLUSION

Providing this information would help consumers make informed decisions about whether to use a particular DTC genetic testing service and, should they choose to pursue testing, understand the implications and limitations of their results.

INTRODUCTION

Falling costs of genetic testing in combination with growing public interest in personal genomics has driven the expansion of direct-to-consumer (DTC) genetic testing. Today’s market encompasses a broad range of offerings, from tests that pair users with wines to tests that reveal serious disease risks.¹ This review focuses on one area of the rapidly expanding DTC market—genetic testing for cancer susceptibility. Within this space, DTC offerings vary considerably in size and scope. The narrowest is a test that screens for three specific mutations in two genes and the broadest is a whole-genome sequencing service that analyzes dozens of genes for mutations that could affect cancer risk.

Traditionally, DTC genetic tests were advertised—and sold—to consumers without involving a health care professional; however, in recent years, a new model of testing has come to dominate the market. In this model, tests are advertised to consumers but ordered by licensed physicians.^2-5 A number of companies even allow consumers to choose between having tests ordered by their own physician or by a company-provided independent physician.

In both the academic literature and the popular media, there is a lack of clarity about which genetic tests count as DTC offerings.⁶ This uncertainty, as Hogarth et al⁷ explain, stems from ambiguity about the meaning of direct-to-consumer, a term that “has been used variously to refer to both advertising and sale of genetic tests.” According to the US National Institutes of Health (NIH), DTC genetic tests “are marketed directly to customers via television, print advertisements, or the Internet, and . . . can be bought online or in stores.”^8(p163) Under this expansive definition, tests that are advertised to consumers but ordered by licensed physicians—often referred to as the hybrid model—fall within the ambit of DTC genetic testing.^2,5

CONTEXT

• Key Objective

• To provide an overview of available direct-to-consumer (DTC) genetic tests for cancer susceptibility and to identify six aspects of the testing process that could affect consumers’ ability to make informed decisions about testing and interpret their results.

• Knowledge Generated

• Recent years have seen DTC genetic testing for cancer susceptibility change dramatically. Specifically, a new model now dominates the market where tests are advertised to consumers but ordered by physicians. Moreover, many of today’s tests are distinguished from earlier DTC offerings for cancer susceptibility by their scope and potential clinical significance. This review provides a comprehensive overview of available DTC genetic tests for cancer susceptibility and identifies aspects of the DTC testing process that could affect consumers’ ability to make informed decisions about testing and understand their results. Given how the DTC genetic testing market for cancer susceptibility has changed in recent years, it is essential that health care professionals and researchers working in this space appreciate both the range of tests being offered and the challenges that consumers may face as they navigate this evolving landscape.

• Relevance

• On the basis of our review of companies’ Web sites, consumers would benefit from more information about certain aspects of the testing process. Providing this information would help consumers make informed decisions about whether to use a particular DTC genetic testing service and, should they choose to pursue testing, understand the implications and limitations of their results.

Other than the shift toward physician-ordered testing, many of today’s tests are distinguished from their predecessors by their scope and potential clinical significance. Previously, in the mid-to-late 2000s, most DTC tests used single-nucleotide variation profiling to assess cancer risk, a process that involves screening a DNA sample for single-nucleotide polymorphisms (SNPs)—single base-pair differences that occur at specific positions in the genome—that may affect cancer risk.^9,10 Single-nucleotide variation profiling, however, tends to have low predictive value for disease risk and limited usefulness in improving health outcomes (ie, clinical utility).

Today’s DTC companies have largely moved away from using single-nucleotide variation profiling. Instead, they tend to analyze specific genes for mutations that increase cancer risk. Yet this change has not eliminated uncertainty in cancer susceptibility genetic testing. For many of the genes included in larger tests, a positive result may be associated with uncertain risk estimates and/or unclear medical management strategies.^11,12

Given how the DTC genetic testing market for cancer susceptibility has changed in recent years, it is essential that health care professionals and researchers working in this space appreciate both the range of tests being offered and the challenges that consumers may face as they navigate this evolving landscape. Part I of this paper provides an overview of available DTC genetic tests for cancer susceptibility as of July 2019. For each test, we discuss cost; who orders it; whether variants of uncertain significance (VUS) are returned; availability of genetic counseling; intended users; whether consumers are recontacted about variant reclassifications; whether the test is characterized by the company as being diagnostic, actionable, and clinically valid; molecular technique used to analyze DNA; and whether the test is Clinical Laboratory Improvement Amendments (CLIA) certified and College of American Pathologists (CAP) accredited.

In Part II, we identify six aspects of the testing process that we believe could affect consumers’ ability to make informed decisions about testing and understand the implications—and limitations—of their results.¹³ These are: how companies use certain terms (eg, medical grade or clinical grade); how companies use consumers’ health information during the ordering process; the extent of genetic counseling provided by companies; companies’ procedures for returning results; the role of company-provided ordering physicians; and companies’ procedures for communicating variant reclassifications. On the basis of our review of companies’ Web sites, we believe that consumers would benefit from more information about these aspects of testing.

PART I: DTC GENETIC TESTS FOR CANCER RISK

Here we describe the array of DTC genetic tests for cancer susceptibility that were on the market as of July 2019 (Table 1). Given the Internet-based nature of DTC genetic testing, today’s consumers primarily receive and interact with DTC companies’ offerings through their Web sites. Thus, to better capture the information that consumers are likely to access when deciding whether to use a test, we only include information about testing services that is, or was, available on companies’ Web sites. It is worth noting that some companies do not explicitly define the terms diagnostic, actionable, or clinically valid. Whereas we describe how each company characterizes these terms and indicate when definitions are absent, inasmuch as our objective is to convey what companies report on their Web sites, we do not evaluate the accuracy of their claims.¹⁴

TABLE 1.

Direct-to-Consumer Genetic Tests for Cancer Susceptibility

23andMe

In 2013, the US Food and Drug Administration (FDA) issued a warning letter to 23andMe (Sunnyvale, CA) ordering the company to discontinue marketing its Personal Genome Service, which included reports for several hundred diseases and conditions, an SNP-based risk score for breast cancer, and a limited BRCA1/BRCA2 test.¹⁵ According to the FDA, 23andMe had failed to demonstrate that its service could correctly identify genetic disease risks, made misleading claims about the health benefits of tests, and failed to comply with the premarket review process for medical devices.¹⁶

Since that time, 23andMe has substantially revised its services. In March 2018, the FDA authorized 23andMe to market a BRCA test that screens for three specific BRCA1/BRCA2 variants, making it the first FDA-authorized DTC genetic test to report on cancer risk.^17,18 Although there are more than 1,000 known BRCA1/BRCA2 mutations that are associated with an increased risk of breast and ovarian cancer, 23andMe’s test only screens for three founder mutations—two in the BRCA1 gene (BRCA1 c.68_69delAG and BRCA1 c.5266dupC) and one in the BRCA2 gene (BRCA2 c.5946delT)—that are found almost exclusively in individuals of Ashkenazi Jewish descent.¹⁷ The test, therefore, is unlikely to be useful to individuals from other ethnic backgrounds.^19,20 As 23andMe acknowledges, its BRCA screen is not comprehensive and does not rule out the possibility that an individual carries one of the many BRCA1/BRCA2 mutations not covered by its report.²¹

In January 2019, 23andMe received FDA clearance to expand its cancer susceptibility testing to report on two MUTYH genetic mutations that are implicated in MUTYH-associated polyposis, an autosomal recessive hereditary colorectal cancer syndrome.²² The two variants that are included in the test—p.Y179C and p.G396D—are the most common pathogenic MUTYH mutations in individuals of northern European descent, although there are more than 100 pathogenic MUTYH variants.²³ In the general northern European, Australian, and US population, the heterozygous carrier frequency for a pathogenic MUTYH variant is 1% to 2%.² Individuals with a single MUTYH mutation are thought to have a slightly increased risk of colorectal cancer relative to the general population lifetime risk—approximately 4%.^25-27 In contrast, individuals carrying mutations in both MUTYH alleles have a much higher cumulative risk of colorectal cancer—approximately 80% by age 70.²⁸

23andMe’s BRCA report is included with its Health + Ancestry Service.²⁹ Excluding special offers, the service costs $199. Consumers order their own tests and receive their results through an online account. If a consumer does not wish to view his or her BRCA result, they can opt to exclude it from the report. Although the company does not provide genetic counseling, consumers are encouraged to consult with a genetic counselor before and after testing. 23andMe uses genotyping to analyze DNA. The company states that its BRCA test meets FDA requirements for clinical validity, which it defines as “the degree to which a test accurately identifies or predicts a disease of interest.”³⁰ 23andMe maintains that its BRCA test “is not intended to diagnose any disease and does not describe a person’s overall risk of developing any type of cancer.”²² It also maintains that the test is not medically actionable and that “[r]esults should be confirmed in a clinical setting before taking any medical action.”²² All DNA samples are processed in CLIA-certified and CAP-accredited laboratories.

Veritas Genetics

Veritas (Santa Clara, CA) offers a whole-genome sequencing service called myGenome Standard that costs $599. For an additional $1,000, consumers can upgrade to myGenome Premium, which includes more diseases and carrier conditions. myGenome (standard and premium) can be ordered by the consumer’s own provider or, for an additional $129, by an independent physician affiliated with the telegenomics company Genome Medical. When the results are ready, Veritas notifies the consumer and the ordering provider, both of whom can then access the report through Veritas’ Web portal. If interested, consumers can pay an additional $99 to receive their raw data.

For myGenome (standard and premium), pathogenic and likely pathogenic results are reported, and benign, likely benign, and VUS results are not typically returned. Veritas does not state whether it will contact the ordering provider or the consumer about variant reclassifications. Through Genome Medical, Veritas offers a complimentary 30-minute return of results genetic counseling session for clinically actionable findings. Consumers can also pay $299 for Comprehensive Genetic Counseling, which includes access to pretest counseling and a 60-minute post-test session to review results.

According to Veritas, its service is intended to be a screening test for healthy individuals; however, myGenome is not meant to be diagnostic because “there is a chance that some of the variants that are associated with health conditions or disease risk could be missed.”³¹ As such, the test “should not be used to diagnose a known or suspected heritable disease in [the consumer] or [the consumer’s family].”³² Veritas does not state whether myGenome is a clinically valid test. It does, however, characterize myGenome as providing information that may “affect [the consumer’s] health and [is] actionable, be it with changes in diet and activity level, medical screenings, or enhanced vigilance.”³³ Nevertheless, it is not clear that Veritas’ findings, at least by themselves, are intended to inform clinical care.³⁴ This interpretation is supported by the company’s informed consent document, which states that “all variants considered clinically relevant in [the consumer’s] report should be confirmed with secondary testing before changes to [the consumer’s] healthcare are made.”³² Veritas uses next-generation sequencing to analyze DNA. The company’s US laboratory is CLIA certified and CAP accredited.

Invitae Corporation

Invitae (San Francisco, CA) offers a cancer susceptibility panel—Invitae Cancer Screen—that consists of 61 genes associated with 10 types of cancer (breast, colorectal, gastric, ovarian, pancreatic, prostate, renal cell, thyroid, uterine, and cutaneous melanoma). In addition, Invitae offers cancer susceptibility testing as part of its Genetic Health Screen, which consists of a 147-gene panel that also analyzes genes related to cardiac diseases and other inherited conditions. Neither test is intended to be diagnostic; both are considered proactive services that are intended for healthy adults without a strong personal or family history of cancer.

Invitae’s Cancer Screen and Genetic Health Screen cost $250 and $350, respectively, and can be ordered by the consumer’s own provider or by a company-provided physician. The ordering provider is notified via e-mail when the results are ready and receives a written report. Consumers who have their test ordered by an independent physician receive an e-mail when the results are ready, at which time they can review their results and schedule an appointment with one of Invitae’s genetic counselors. Post-test genetic counseling is available at no additional cost.

Invitae uses next-generation sequencing and does not report VUS findings for proactive tests. However, if a VUS is reclassified to likely pathogenic or pathogenic, Invitae will inform the ordering physician and issue an updated report. Invitae does not say whether it will contact the ordering physician and issue an amended report for other variant reclassifications. The company also does not state whether either proactive test is clinically valid, although it does provide links to validation studies.³⁵ Regarding actionability, Invitae maintains that consumers can “take action based on [their] results” and “work with [their] provider to consider: increased or earlier screenings, lifestyle modifications, and early intervention to prevent the onset of disease.”³⁶ Invitae’s laboratory is CLIA certified and CAP accredited.

Color Genomics

Color Genomics (Burlingame, CA) offers a test called Color Extended that analyzes genes related to cancer, cardiac disease, and medication response. The test costs $258.95 and includes 30 cancer predisposition genes associated with eight types of cancer (breast, ovarian, uterine, colorectal, melanoma, pancreatic, stomach, and prostate). Color Extended can be ordered by either the consumer’s own provider or by a company-provided independent physician at no additional charge. If the consumer’s own provider orders the test, the provider can choose whether the results are released to the consumer as soon as they are ready or after a delay. For tests that are ordered by an independent physician, information about the process for returning results is not available on the company’s Web site. Consumers who wish to discuss their results can access complimentary genetic counseling.

Color uses next-generation sequencing and reports VUS findings. If a VUS result is reclassified, Color will attempt to recontact the consumer. The company does not state whether Color Extended is a clinically valid test in its entirety. However, there is a section on the Web site where Color discusses the clinical validity of its tests with respect to certain conditions.³⁷ Color Extended is described as being actionable, meaning that the consumer can “work with [their] healthcare provider to create a personalized screening and prevention plan, designed to reduce [their] risk of developing cancer.”³⁸ Color maintains that its test is not diagnostic because “[p]ositive results do not necessarily mean that [the consumer] [has] that hereditary disorder or that [the consumer] will develop the disorder in [their] lifetime” and “[n]egative results do not eliminate [the consumer’s] risk of developing a disorder, and do not guarantee that [the consumer] will be healthy or will never develop any of the disorders that Color tests for.”³⁹ Color’s laboratory is CLIA certified and CAP accredited.

Helix

Helix (San Carlos, CA) offers two tests—GenePrism and Prostate Cancer Genetic Risk Score—that evaluate cancer susceptibility. Whereas both tests are sold by Helix, GenePrism is administered by PerkinElmer Genomics, and Prostate Cancer Genetic Risk Score is administered by NorthShore University HealthSystem. The tests can only be ordered by a physician who is affiliated with the relevant partner company.

GenePrism analyzes the 59 genes included in the American College of Medical Genetics and Genomics’ list of actionable genes, of which 26 are associated with an increased risk of cancer.⁴⁰ The test costs $299.99, including a $30 fee that covers the ordering physician and genetic counseling services. The test is “intended to provide proactive health insights for those who do not have a significant family history associated with the health conditions that it includes.”⁴¹ The consumer is notified by e-mail when the results are ready to be accessed through the GenePrism Web site. Helix does not explicitly state whether the test is clinically valid. GenePrism is not a diagnostic test and “is not intended to diagnose any medical conditions” and “will not tell you if you currently have one of the conditions covered by the test, or if you definitely will or will not develop the condition in the future.”⁴¹ The test does not report VUS results. Helix describes the test as actionable, which, according to the company, means that “if [the consumer] learn[s] of a genetic risk from the test, [the consumer’s] risk is significantly increased over the general population, and there are actions [the consumer] or [the consumer’s] doctor can take to reduce [the consumer’s] risks based on established medical recommendations.”⁴¹ Helix does not explain its procedures for recontacting consumers about variant reclassifications, although the company does maintain that “[r]esults may change as research continues to allow us to better interpret what these and other genes mean for health.”⁴¹

Prostate Cancer Genetic Risk Score is an outlier among DTC cancer susceptibility tests. Unlike other tests that focus on single-gene mutations, Helix’s test provides a polygenic risk score based on an analysis of numerous SNPs that affect prostate cancer. The test costs $239.99, which includes a $40.00 fee that covers the ordering physician and genetic counseling services. Helix does not state whether the test is intended for individuals with a personal and/or family history of prostate cancer. Results are returned through secure e-mail. Helix maintains that the test is not a diagnostic product because “[a]n estimate of [the consumer’s] risk does not determine if [the consumer] will or will not get prostate cancer.”⁴² Helix does not state whether the test is clinically valid or whether results are medically actionable.

Helix uses next-generation sequencing to analyze DNA. For both GenePrism and Prostate Cancer Genetic Risk Score, genetic counseling is available through Genome Medical at no additional charge. Helix’s laboratory is CLIA certified and CAP accredited.

PART II. ASPECTS OF TESTING THAT COULD AFFECT INFORMED DECISION MAKING AND THE INTERPRETATION OF RESULTS

Meaning of Terms

In describing their offerings, several companies use terms that they do not clearly define. For example, Invitae characterizes its proactive tests as medical grade and diagnostic grade. Except to say that its proactive tests “offer the same clinical quality as a diagnostic test,” the company does not explicitly define either of these terms.⁴³ Similarly, Color characterizes its offering as an “affordable clinical-grade test,” but does not specify what the term clinical grade means. Of note, despite describing these tests as medical, diagnostic, or clinical grade, both Invitae and Color maintain that their services are not intended to be diagnostic.^39,43 Consumers who are unclear about the meanings of these terms, none of which are scientific or medical designations, may struggle to understand why a test that is marketed as medical-, diagnostic-, or clinical grade should not be used in a diagnostic capacity.

In addition, given that tests are often characterized as being medical, diagnostic, or clinical grade, consumers may wonder whether their results could expose them to potential insurance discrimination. According to the Genetic Nondiscrimination Act (GINA), it is illegal for US health insurance providers to use genetic information, including from DTC tests, to deny coverage or increase premiums. GINA, however, does not apply when an employer has fewer than 15 employees or to other forms of insurance (eg, disability insurance, long-term care insurance, and/or life insurance).⁴⁴ Although all of the companies seem to provide some information on their Web sites about genetic discrimination, discussions about how consumers’ results could affect their access to different types of insurance is often covered during pretest counseling, which may be lacking in the DTC setting.

Companies could also be more transparent about whether their tests can accurately predict an individual’s risk of developing a particular disease—that is, whether they are clinically valid. Most DTC cancer susceptibility genetic tests analyze an array of genes that encompass a wide range of risk estimates. Whereas some of the genes included in these tests have well-established risk estimates, not all do. For example, Color and Veritas’ tests include the MITF gene.^45,46 Although MITF mutations are suspected to increase the risk of melanoma and renal carcinoma, the extent to which a mutation carrier’s risk is elevated remains unclear.^45,47 Overall, consumers might benefit from greater clarity about which genes in a test are considered clinically valid. Providing this information in a transparent and accessible manner could help consumers decide whether to pursue a test that may include genes with low predictive value for cancer risk.

Use of Consumers’ Health Information

Companies with testing services that can be ordered by a company-provided physician often ask consumers to answer a set of questions about their personal and family health history; however, it is not always clear how ordering physicians use this information. For example, Veritas maintains that consumers’ responses to these questions “are necessary to sequence [their] DNA and also helps [Veritas] better interpret [their] results.”⁴⁸ Nevertheless, Veritas does not clarify how this information factors into the ordering process. As consumers consider whether to purchase a test, they may be interested in learning how their health information will be used. In particular, they might want to know whether the physician will follow up to discuss their health history before ordering testing. Consumers might also wonder whether company-provided physicians ever decline to order testing and, if so, for what reasons.

Genetic Counseling

Although all of the companies that offer physician-ordered DTC genetic tests seem to provide genetic counseling in some capacity, the extent, timing, and cost of these services is sometimes unclear. For example, Invitae maintains that “[o]ur team of board-certified genetic counselors is available on demand by phone during business hours to assist you with general questions about genetic testing and your results.”⁴⁹ What remains unclear (for Invitae and some of the other companies) is the extent to which pretest counseling is comprehensive and individualized. In the clinical setting, pretest counseling is widely regarded as an important part of obtaining informed consent to testing.^50,51 Companies could therefore help consumers make informed choices about whether to pursue DTC testing by including more information on their Web sites about pretest counseling.

Currently, companies differ in terms of how they provide genetic counseling. Helix, for example, outsources its genetic counseling to Genome Medical, which is a distinct corporate entity from Helix.⁴¹ Other companies, such as Invitae, offer in-house counseling that includes pretest counseling.⁴⁹ This arrangement raises potential ethical concerns about whether a conflict of interest arises when companies provide pretest counseling services for their own tests.^52,53

Procedures for Returning Results

Most of the companies that offer tests through the physician-ordered model do not include a detailed description of their process for returning results. On the basis of the companies’ online materials, it may not be clear whether procedures vary depending on the clinical significance of consumers’ results. Are positive and VUS results disclosed over the phone by a genetic counselor, while negative results are delivered through an online portal? Again, providing more information could help consumers make informed decisions about whether they are comfortable with a company’s model for returning results.

Role of Company-Provided Physicians

For some of the companies that offer company-provided independent physicians, it is unclear what role, if any, these physicians play beyond simply ordering tests. It is also not clear how companies conceive of the relationship between consumers and these physicians, some of whom may belong to an external physician network or separate company.⁵⁴ For example, Helix states that the company “will share [the consumer’s] contact information and health history with PerkinElmer Genomics so a physician they designate can review and make sure this product is right for [the consumer].”⁴¹ Consumers may wonder whether they can contact the ordering physician with additional questions about the test or their results. Notably, will the ordering physician assume responsibility for a consumer’s follow-up care or refer the consumer to another provider? As of now, these questions are not easily answerable from companies’ online materials.

Variant Reclassification

As scientific understanding of variant pathogenicity evolves, genetic test results may be amended. Some changes could have significant clinical implications for disease risk and medical management (eg, a VUS that is upgraded to pathogenic). Nevertheless, information about companies’ procedures for handling amended results may not be readily available. Color’s Informed Consent, for instance, lacks specific information about how the company manages variant reclassification beyond stating that it may “at its sole discretion, amend or modify [the consumer’s] Test report” and will “attempt to notify (the consumer) of any material amendments or modifications.”³⁹ Some companies, however, do not provide any information about variant reclassification. Helix’s informed consent, for instance, notes that “future information may change your results,” but does not specify whether the company monitors for variant changes or notify consumers about them.⁵⁵ Given the potential clinical significance of variant reclassifications, consumers could benefit from more information about companies’ procedures for tracking variant changes and sharing amended results.

In conclusion, genetic testing for cancer susceptibility, once limited to the clinical setting, is now widely available through Web-based DTC genetic testing companies. To better understand whether test takers are knowledgeable about companies’ testing procedures, there is an urgent need to collect and study consumer outcome data.¹³ As the DTC market continues to evolve, outcome data should inform companies’ products and practices to ensure that consumers are equipped to make informed decisions throughout the testing process and understand their results.

AUTHOR CONTRIBUTIONS

Conception and design: All authors

Collection and assembly of data: Madison K. Kilbride

Data analysis and interpretation: Madison K. Kilbride

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Angela R. Bradbury

Consulting or Advisory Role: AstraZeneca, Merck

No other potential conflicts of interest were reported.