Genetics healthcare providers' experiences counseling patients with results from consumer genomic testing

Abstract

Background

Consumer genomic testing (CGT), including direct‐to‐consumer and consumer‐initiated testing, is increasingly widespread yet has limited regulatory oversight. To assess the current state, we surveyed genetics healthcare providers' experiences with CGT.

Methods

A retrospective survey about experiences counseling on CGT results was completed by 139 respondents recruited from the National Society of Genetic Counselors, Clinical Cancer Genomics Community of Practice, and genetics professional societies.

Results

Among respondents, 41% disagreed with the statement that potential benefits of CGT outweigh harms, 21% agreed, and 38% were undecided. A total of 94% encountered ≥1 challenge counseling CGT patients, including adverse psychosocial events (76%), incorrect variant interpretation (68%), and unconfirmed results (69%); unconfirmed results were more common among oncology providers (p = 0.03). Providers reporting higher total challenge scores (p = 0.004) or more psychosocial or interpretation challenges (p ≤ 0.01) were more likely to indicate CGT harms outweigh benefits. Those with higher CGT clinical volume were more likely to indicate benefits outweigh harms (p = 0.003). Additional CGT challenges included patient understanding and communication of results, false negatives, incorrect testing/care, and financial costs; seven respondents (6%) documented positive outcomes.

Conclusion

Providers counseling CGT patients encounter psychosocial and medical challenges. Collaborations between regulators, CGT laboratories, providers, and consumers may help mitigate risks.

Survey data suggest that genetics healthcare providers encounter various psychosocial and medical challenges when counseling patients on results obtained from consumer genomic testing, including direct‐to‐consumer and consumer‐initiated testing for cancer and other health‐related risks. Collaborations between regulators, laboratories, providers, and consumers may help mitigate risks.

1. INTRODUCTION

Traditionally, individuals undergoing genetic testing for a personal or family history of disease receive pre‐test genetic counseling to facilitate informed consent followed by post‐test counseling to ensure appropriate results interpretation and medical management (Patch & Middleton, 2018). This pre‐ and post‐test counseling model was historically used to uphold the ethical principles of beneficence and autonomy and enable informed consent by addressing potential benefits as well as risks of testing. Potential risks included significant psychological distress (including theoretical concerns of suicide), loss of confidentiality, insurance discrimination, false positive or false negative results, and limited efficacy of medical interventions (Bird, 1999). In broad practice these initial concerns have been largely averted, particularly in cancer genetic testing (Wade, 2019). Recently, in the United States many direct‐to‐consumer (DTC) laboratories as well as laboratories that had avoided the DTC approach have embraced a consumer‐initiated testing model whereby a client obtains self‐directed testing either by requesting it from their own healthcare provider or a provider affiliated with the testing laboratory itself, who may or may not have expert knowledge. This approach appears to sidestep much of the standard regulatory authority of the U.S. Food and Drug Administration (FDA; Offit et al., 2023).

Collectively known as consumer genomic testing (CGT), DTC genetic testing and consumer‐initiated testing for cancer and other health‐related risks have begun to shift the paradigm while posing substantial clinical challenges because of the surgical as well as medical implications of many consumer‐initiated tests (Offit, 2011). CGT results are infrequently shared by consumers with their healthcare providers (Makhnoon et al., 2022; Martins et al., 2022). Among those who do share results, many express dissatisfaction with the encounter (van der Wouden et al., 2016), possibly related to inflated marketing promises by CGT companies (Burke & Trinidad, 2016). CGT results induce modest to no changes in perceived cancer risk, lifestyle modifications, or screening practices (Carere et al., 2015; Gray et al., 2017; Roberts et al., 2017; Stewart et al., 2018). Perhaps for these or other reasons, with short term follow‐up of consumers themselves, approximately 2% of 1000 respondents reported regret or harm following consumer‐initiated genetic testing (Gray et al., 2017).

One impetus for the current survey is that measurement of actual harm following CGT may require follow‐up of healthcare providers who eventually are called to counsel those who receive CGT. Provider as well as consumer input is needed to document efficacy and consequences of CGT. For example, despite wide consumer uptake, CGT for cancer risk raised immediate provider concerns relating to clinical utility and false negatives. FDA market authorization for MUTYH testing by one DTC laboratory occurred despite medical opinion that heterozygote detection, other than for recessive carrier detection, offered no clinical actionability for colon cancer risk management (National Comprehensive Cancer Network, 2022). Similarly, authorization for DTC Ashkenazi Jewish (AJ) BRCA1 and BRCA2 founder pathogenic variant (mutation) testing can lead to false reassurance for the vast majority of the population which is not of AJ ancestry (Esplin et al., 2019). Subsequently reports from cancer testing and other practitioners have documented unnecessary prophylactic surgeries, inappropriate testing of minors for adult‐onset conditions, false reassurance, and increased emotional distress from unexpected or conflicting reports (Dinulos & Vallee, 2020; Domchek et al., 2020; Offit et al., 2023; Predham et al., 2016). Other than these anecdotal reports, surveys of providers caring for individuals who have received CGT have been limited. To better understand the current perception of CGT among those in the genetics community agreeing to share their assessments, we surveyed healthcare providers' experiences with CGT in onco‐genetics and other clinical settings.

2. MATERIALS AND METHODS

2.1. Ethical compliance

This study was reviewed and approved by the Institutional Review Board of Memorial Sloan Kettering Cancer Center (MSK). The MSK Institutional Review Board approved this study as exempt research; therefore, all respondents confirmed agreement with their voluntary willingness to participate by completing the survey.

2.2. Survey

For this study, a 10‐question anonymized retrospective survey was developed based on literature reviews and clinician experience (Offit et al., 2023; see Appendix). The survey included investigator‐designed, face valid items to assess respondents' clinical role and area of focus, whether they had ever counseled individuals after DTC genetic testing or consumer‐initiated testing within the past 3 years, and the overall patient volume as well as volume within the setting of cancer risk for CGT cases. An additional item assessed the frequency with which respondents had encountered a set of six possible challenges regarding CGT selected based on the study team's clinical experience and literature review, along with one open‐ended item asking respondents to elaborate in free text on their experiences with the listed challenges or adverse events not listed. The survey also assessed their overall view of whether the potential benefits of CGT accrued to their patients outweighed the potential harms. As an exploratory question about a form of testing that has potential to be available via CGT and to direct future research, respondents were asked whether they had ever consulted on interpretation of a circulating tumor (cell‐free or “liquid biopsy”) DNA result. This question was posed to participants without additional contextualization regarding the reasons for which the circulating tumor DNA test was conducted. The survey was created using REDCap.

2.3. Sampling and recruitment

A link to the survey was distributed to healthcare professionals through email lists and board postings of the National Society of Genetic Counselors, the Clinical Cancer Genomics Community of Practice at City of Hope, and other genetics‐focused professional societies (including societies based at Sarah Lawrence College, Southern California, Illinois, Connecticut, New Jersey, and the Jewish Genetic Counselors Group). Membership in these national and regional organizations comprises >5700 genetic specialists, largely physicians and genetic counselors, from various disciplines.

2.4. Data analysis

Statistical analyses were conducted with IBM SPSS Statistics 27. Descriptive statistics were computed for all variables. Analyses were conducted to determine if respondents' overall view of whether the benefits of CGT outweigh the harms differed based on their area of clinical focus, CGT patient volume, and frequency of CGT challenges. Due to the nonnormal nature of the data, survey responses were analyzed using independent‐samples Kruskal–Wallis H tests and Dunn–Bonferroni pairwise comparisons. Respondents' answers to their overall view of whether the benefits of CGT outweigh the harms (yes, no, or undecided) and area of clinical focus (oncology or non‐oncology) were treated as factor variables; CGT patient volume and CGT challenge frequency were treated as continuous. A “total challenge score” was also calculated for each respondent by summing their six challenge question responses. A Mann–Whitney U‐test was used to assess differences in CGT challenge frequency between areas of clinical focus. All completed items in each survey were included in the analyses. Answers to the open‐ended item asking respondents to elaborate on any CGT challenges were analyzed using qualitative inductive analysis (Green & Thorogood, 2018). First, the responses were reviewed and categorized as reflecting challenges listed in the survey or novel challenges by members of the study team (J.G.H., K.O., M.T., and D.G.). Next, a team member (J.G.H.) performed an in‐depth review of each response to assign it codes based on the challenges listed in the survey or to develop and apply new codes reflecting novel challenges described by respondents. To mitigate bias, a second team member who was not involved in the study conceptualization or survey development (H.O.) reviewed these codes to determine if there were any perceived discrepancies, which were resolved by consultation between team members.

3. RESULTS

In total, 139 respondents completed the survey from February to March 2022, of which 123 (88.5%) identified as a genetic counselor (GC) and the remaining (n = 16; 11.5%) as an MD/DO physician or other healthcare professional (Table 1). A majority (n = 86; 61.9%) selected oncology as an area of clinical focus. Of 138 respondents who provided an answer to the question of whether they had ever consulted on interpretation of a circulating tumor DNA result, 34.1% had encountered this type of referral. A total of 122 (87.8%) respondents reported counseling individuals after CGT within the past 3 years and were therefore eligible for further analysis. Of these respondents, most had counseled approximately 1–5 patients (n = 59; 48.8%) or 5–10 patients (n = 32; 26.4%) after CGT in the past 3 years. Respondents estimated that approximately half of these cases (M = 51.82, SD = 44.42) were for cancer risk counseling.

TABLE 1.

Characteristics of survey respondents (n = 139).

	n (%)
Healthcare professional type
Genetic counselor	123 (88.5)
M.D. or D.O. physician	7 (5)
Other healthcare professional	9 (6.5)
Specialty: multi‐select
Cancer	86 (61.9)
Prenatal	27 (19.4)
Pediatric	21 (15.1)
Neurogenetics	10 (7.2)
Cardiogenetics	18 (12.9)
General medical	29 (20.9)
Other	13 (9.4)
Specialty: dichotomous
Cancer	86 (61.9)
Non‐cancer	52 (37.4)
Missing	1 (0.7)
Counseled individuals after DTC/CIT in the past 3 years
Yes	122 (87.8)
No	17 (12.2)
Approximate number of patients counseled after DTC/CIT*
1–5	59 (48.8)
5–10	32 (26.4)
10–25	17 (14.0)
20–50	3 (2.5)
Over 50	10 (8.3)
Missing	1 (0.8)
On balance, do you feel that the potential benefits of DTC/CIT accrued to your patients outweigh the potential harms?*
Yes, benefits outweigh harms	25 (20.8)
No, harms outweigh benefits	49 (40.8)
Undecided	46 (38.3)
Missing	2 (1.6)

	n	Mean %	SD
Approx. percentage of cases seen for*
Cancer risk counseling	119	51.82	44.42
Risk counseling of other heritable diseases	120	38.85	42.19

^*Only respondents who reported counseling individuals after DTC/CIT in the past 3 years are included.

When asked whether the potential benefits of CGT outweigh potential harms, 40.8% of respondents disagreed, 20.8% agreed, and 38.3% were undecided. Respondents who reported a higher CGT patient volume were more likely to agree that benefits outweigh harms (H(2) = 11.43, p = 0.003). Area of clinical focus was not significantly associated with this view.

When presented with six potential challenges that may arise with CGT (Figure 1), 94.1% (112/119) of respondents indicated having some level of experience with at least one of the challenges. The most frequently encountered (i.e., endorsed by respondents as “sometimes,” “often,” or “always”) challenge was testing leading to an adverse psychosocial event that could have been ameliorated by pre‐test genetic counseling (90/119; 75.6%). This was followed by 68.7% (79/115) who reported inability of a reference laboratory to confirm results directly reported to patients based on data input into third‐party interpretation (TPI) services (i.e., result derived from raw CGT data interpretation), and 68.4% (80/117) reporting incorrect variant interpretation on the CGT report (e.g., interpretation of variant's significance or actionability was incorrect). In comparison to non‐oncology providers, oncology providers reported higher occurrences of a CGT result not being confirmed after testing in a reference laboratory (U = 1995, p = 0.031).

FIGURE 1.

Provider experiences with six potential consumer genomic testing (CGT) challenges. CIT, consumer‐initiated testing; DTC, direct‐to‐consumer.

Frequency of encountering the challenges of adverse psychosocial events and incorrect variant interpretation were significantly related to overall views of CGT (H(2) = 15.18, p < 0.001; H(2) = 9.27, p = 0.01, respectively). Pairwise comparisons found that respondents who did not feel that the benefits of CGT outweigh the harms reported experiencing both events more frequently than those who agreed or were undecided. Table 2 summarizes the average frequency scores for all six challenges, stratified by respondents' overall views of CGT. Views of CGT were also significantly related to total challenge scores (H(2) = 11.20, p = 0.004). Those who did not feel that the benefits of CGT outweigh the harms had higher total challenge scores, on average, than those who agreed that benefits do outweigh harms (11.88 vs. 9.52; p = 0.001).

TABLE 2.

Frequency of encountering DTC/CIT‐related challenges, stratified by respondents' overall views of CGT.

	Yes, benefits outweigh harms	No, harms outweigh benefits	Undecided	Total sample
Patient's result from DTC/CIT was not confirmed when repeated in a reference lab	1.65 ± 0.83	1.96 ± 1.04	1.96 ± 1.04	1.90 ± 1.00
Patient's derived result from DTC/CIT was run through a third‐party algorithm or database and produced a result that would not be confirmed in a reference lab	1.83 ± 0.78	2.35 ± 1.01	2.12 ± 1.03	2.16 ± 0.99
Patient's DTC/CIT analytic interpretation of the test result was incorrect	1.73 ± 0.77*	2.24 ± 0.86	1.83 ± 0.85*	1.98 ± 0.86
Cases of DTC/CIT testing of a minor‐aged child	1.42 ± 0.58	1.37 ± 0.67	1.26 ± 0.44	1.34 ± 0.57
Cases where DTC/CIT testing led to inappropriate medical care	1.30 ± 0.47	1.45 ± 0.68	1.62 ± 0.72	1.49 ± 0.67
Cases where DTC/CIT testing led to an adverse psychosocial event that could have been ameliorated by pre‐test genetic counseling	1.67 ± 0.70**	2.51 ± 0.92	2.04 ± 0.82*	2.16 ± 0.89

Note: Respondents who reported counseling individuals after DTC/CIT in the past 3 years (n = 122) were asked to indicate approximately how often they encountered each challenge. Response options ranged from 1 (never) to 4 (always), with higher values reflecting more frequent occurrence. Values are expressed as mean ± standard deviation.

Note: Differences were significant (Bonferroni‐adjusted) at *p < 0.05 and **p < 0.01 compared to the “Harms outweigh benefits” group.

A total of 46 respondents provided answers to the open‐ended item allowing for elaboration on any CGT‐related challenges. As shown in Table 3, respondents most often described challenges that were listed in the survey, including adverse psychosocial events (n = 13) and issues with raw data TPI (n = 13). However, various novel challenges were also described. These included challenges with patient understanding or willingness to accept the provider's interpretation of the CGT results (n = 13), situations where the CGT result was determined to be a false negative (n = 7), concerns about ineffective communication of CGT results between patients and their other healthcare providers (n = 5), concerns about financial costs incurred by patients (n = 4), and a situation in which a medically incorrect test was ordered for a patient through CGT (n = 1). Of note, multiple respondents described positive outcomes of CGT such as the provision of information to adopted individuals and improved access to testing (n = 7).

TABLE 3.

Codes, definitions, number of times code was applied, and illustrative participant responses regarding CGT‐related challenges.

Code	Definition	Frequency	Exemplar quotation(s)
Adverse psychosocial event	Cases where CGT led to an adverse psychosocial event that could have been ameliorated by pre‐test genetic counseling (e.g., extreme distress or anxiety)	13	“Adverse psychosocial event: A patient was taken by surprise and distressed when she tested positive for a BRCA variant through DTC testing ([Company A]). She didn't really realize she was being tested for this. On the other hand, she would not otherwise have qualified for testing and may never have pursued it, so she had mixed feelings (including gratitude) about having found out this way.” (ID 52) “I've had patients come in with a TP53 VUS that they thought was pathogenic. They were hysterical after surfing the internet. Others didn't understand test results.” (ID 132)
Issues with third party raw data interpretation	Patient's derived result from CGT was run through a third‐party interpretation service (e.g., for raw data interpretation) and produced a result that could not be confirmed in a reference laboratory	13	“One of my patients had DTC testing completed that showed no pathogenic variants. But this patient entered data into a 3rd party site, and was overwhelmed by how many pathogenic variants it said they had. I reviewed the reference numbers (rs######) by looking those up in ClinVar and dbSNP to see if I could gather any more information on if these were commonly miscalled by DTC labs. The patient did a comprehensive cancer genetic testing with me through a CAP/CLIA lab, and their results were negative. When I disclosed their results, I do not know if she believed me because she had worked herself up so much over the 3rd party site report.” (ID 23) “Patient's results were through third‐party database that classified APC I1307K as diagnostic of FAP.” (ID 68)
Inappropriate medical care	Cases where CGT led to inappropriate medical care (e.g., prophylactic surgery, insufficient screening or follow‐up)	4	“Four patients were directed to have prophylactic risk reducing surgery for a VUS. Two of those patients had the surgery before coming to me for counseling. None of the patients had pretest counseling. None understood possible impact of testing before testing. All needed corrective risk assessment counseling.” (ID 126)
Minor testing	Cases of CGT of a minor‐aged child	4	“I counseled a patient who ordered direct‐to‐consumer genetic testing for all of [their] children. One of the children was reported to have a gene variant consistent with Lynch syndrome (an adult‐onset cancer predisposition syndrome). This child was 3 years old. This led to some ethical concerns and was a difficult counseling session.” (ID 11)
Result not confirmed	Patient's result from CGT was not confirmed when repeated in a reference laboratory	4	“Only 1 patient was seen by me in the last year, and it was ancestry‐based testing. However, this patient's DTC results identified Y chromosome material; patient was assigned female at birth. We did clinical chromosome analysis which yielded 46,XX. This patient had already connected with “relatives” (we discussed possibility of sample swap) identified by DTC testing (patient was adopted), and had thought that the Y chromosome presence would explain why he identified as male. I wouldn't go so far as to say extreme distress resulted, but DTC results definitely caused some distress.” (ID 106)
Challenges with patient understanding	Difficulties with the patient accurately understanding or accepting the genetic healthcare provider's interpretation of the CGT result	13	“In terms of the analytic interpretation: Often the report was technically correct but the patient mis‐understood the information and so believed their findings were medically significant when they were not.” (ID 31) “Most challenges are related to patients not understanding results/want more clarity. Some patients frustrated with lack of actionability of DTC results (particularly related to disorders for which routine clinical confirmation is not indicated/available—MTHFR)” (ID 37)
False or misleading negative	CGT results are determined to be a false negative or a misleading negative result (e.g., due to incomplete testing, failure to consider personal/family history)	7	“Patients used DTC for carrier screening for CF without understanding the residual risk. [Company B] testing reported they were NOT a CF carrier, then individual had a child with CF and was shocked as to how it could have occurred.” (ID 19) “I've had several that said they tested neg for BRCA1/2 on [Company A testing], but did not understand the limitations of the test and the need for clinical testing of other variants.” (ID 116)
Positive outcome	Description of positive or beneficial outcomes of CGT (e.g., information for adopted individuals, improved access)	7	“…On the other side of the fence: I counseled a patient for cancer risk who had ‘ordered her own test’ at a lab I use frequently. (Test was actually ordered by a contracted independent physician, similar to [a CIT] model). Pt tested for connective tissue disorders, trying to diagnose Hypermobile EDS. She seemed to understand that the negative 40‐gene panel did not rule in or rule out hEDS. And she got genetic testing much faster than she could have in our local market. Overall this seemed a benefit to patient on a ‘personal utility’ level…” (ID 48) “I have consulted with several individuals who have used DTC genetic ancestry testing to help find relatives and inform them of hereditary cancer risk that was initially identified through clinical genetic testing. This use of family history genetics for cancer prevention is a creative and potential beneficial use of DTC genetic testing.” (ID 95)
Concerns about communication with other providers	Concerns about inaccurate or incomplete communication regarding CGT results between patients and their other healthcare providers (e.g., primary care providers)	5	“PCP encouraged male patient who has a sister (affected: ovarian cancer, found to have BRCA1 AJ founder mutation on clinical testing from a commercial lab) to pursue [Company A testing] because ‘he wouldn't be able to get clinical testing as a man.’ When he tested positive for a BRCA1 mutation on [Company A testing], PCP did not tell patient that it should be confirmed clinically…” (ID 62)
Financial concerns	Concerns about financial costs incurred by patients that are related to or stem from the CGT	4	“…The second was an elderly couple whose daughter had run her data through a third‐party company ([Company B]) that gave non evidence based recommendations about dietary supplements. The couple then spent hundreds of dollars to do the same testing for themselves, then came to us distressed that Medicare did not cover the cost of the many expensive supplements that were recommended. This family suffered significant financial harm due to incorrect interpretation and lack of pretest counseling.” (ID 97)
Incorrect test	Incorrect CGT was ordered for a patient as interpreted by the genetic healthcare provider	1	“The incorrect testing was ordered and patient was given false reassurance from negative results.” (ID 79)

Note: Codes are based on review of open‐ended responses from 46 participants who provided analyzable data in response to the question “If desired, please elaborate on any of the challenges indicated above (please do not use protected health information). You may also describe any other adverse event not listed above.”

Note: Blue‐shaded cells indicate codes derived from questions included in the survey itself, whereas orange‐shaded cells indicate novel codes deduced from participant responses. Individual responses/quotations could be labeled with more than one code.

Abbreviations: AJ, Ashkenazi Jewish; PCP, primary care provider; VUS, variant of uncertain significance.

4. DISCUSSION

Consumer genomic testing (CGT), either direct‐to‐consumer or through a consumer‐initiated outreach to a healthcare provider, is increasingly marketed by for‐profit commercial laboratories or raw data interpretation services (Offit et al., 2023). In the absence of comprehensive regulatory oversight of entities providing laboratory developed tests of inherited disease susceptibility, no universal reporting guidelines exist for consumers or providers to document the frequency of analytic or interpretation failures, or other adverse effects, in the context of CGT. While the nascent literature has documented clinical instances of adverse events following CGT, efforts to survey specialty providers of genetic services have been limited. Here we report on a voluntary and anonymous survey of the members of several groups of genetic counselors and physicians who provide genetic testing services, including cancer genetic testing.

Notably, 94% of providers indicated that they had faced at least one of several identified challenges when counseling patients on CGT results. The most commonly cited challenge across the quantitative and qualitative data was adverse patient psychosocial effects. Examples from our own clinical experience included two young females who pursued DTC testing for recreational, non‐medical, purposes. In both cases, there was receipt of results of a BRCA pathogenic variant despite no recall of receiving cancer risk counseling or education before or after testing. In one case, there was significant psychological adverse sequela on receipt of results, compounded by the discovery she was conceived by sperm donation. In the other case, psychological distress led to failure to discuss findings with a healthcare provider, and a delay of over a year before initiating cancer surveillance by which time she had a locally metastatic tumor (Offit et al., 2023). Survey respondents similarly described examples of patient psychosocial issues related to receiving unexpected medical or other results from CGT (e.g., unexpected hereditary cancer syndrome or sex‐chromosome result, unexpected discovery of misattributed paternity), as well as examples of distress while seeking to self‐navigate for education and support following disclosure of results that posed imminent threats to health and well‐being (e.g., encountered by an individual with a TP53 pathogenic variant). Even after undergoing confirmation testing in a reference laboratory, providers described cases where patients struggled to accept that a CGT result was falsely positive or inaccurately classified. Setting appropriate expectations and presenting limitations of testing, either by traditional pre‐test genetic counseling, or via novel approaches to personalized online education, support, or tailored post‐test genetic counseling (Koerner et al., 2023; Schmidlen et al., 2018; Schmidt et al., 2019; Webster et al., 2023), may have mitigated the psychosocial issues faced by these individuals.

The next most commonly cited challenge in the quantitative and qualitative data related to analytic failure (i.e., inability to confirm results from CGT). An example from our clinical experience involved a female scheduled for risk‐reducing surgery based on a report of a BRCA1 variant that was miscalled as pathogenic by a CGT laboratory that outsourced their bioinformatic and interpretive processes. In the present study, respondents with an oncologic focus were significantly less likely to be able to confirm a CGT result when repeated in a reference laboratory, which is of particular concern given other reports of surgical risk‐reducing strategies planned based on errant CGT reports in the context of common hereditary cancer syndromes but averted (Horton et al., 2019; Offit et al., 2023). Such reports have served as one impetus for increased regulation by the FDA of laboratory developed testing (Food and Drug Administration, 2023). However, the most common analytic challenge reported in this survey related to results provided by third party interpretation services (TPI). TPI is available to individuals and is increasingly being used by consumers to obtain their raw genomic data from CGT companies. This raw data may contain unvalidated genotyping, or genotyping inferred from single nucleotide polymorphisms (SNPs) which are then matched against “normal” entries in databases. Although many consumers utilizing TPI are motivated by health implications (Wang et al., 2018), inaccurate information can be obtained. For example, an incorrect result may be reported if the “normal” reference set to which a SNP is being compared is incomplete or not properly matched based on population ancestry. There are accumulating reported cases of errant third‐party data analysis (Offit et al., 2023; Tandy‐Connor et al., 2018) including one in a major news outlet documenting discordant results relating to risk of early‐onset Alzheimer's disease based on TPI services of data derived from an ancestry analysis (Hercher, 2018). These findings underscore the important role the FDA may play by including TPI services in the regulatory scope being developed for laboratory developed tests (Food and Drug Administration, 2023; Offit et al., 2023).

Survey data also identified frequent experiences among healthcare providers noting inaccurate determination of the clinical actionability of a CGT finding. Interpretative errors may occur when a variant is correctly sequenced, but the classification of the variant as pathogenic (disease‐causing) or benign is incorrect. For example, an unnecessary, irreversible risk‐reducing surgery was described by one survey respondent in the setting of a patient with a variant of uncertain significance (VUS) CGT result. These types of errors can arise if a laboratory does not have a well‐established variant calling pipeline, or poor curation services, but it may also occur simply as a result of a difference of opinion among testing laboratories. Such disparities in laboratory reporting in some cases may lead to provider recommendations to seek surgical procedures that are not indicated (e.g., for VUS; Balmaña et al., 2016; Domchek et al., 2020), or incorrect management due to inappropriate genotype–phenotype curation (e.g., association of Li‐Fraumeni Syndrome with a CHEK2 pathogenic variant; Offit et al., 2023). Thus, even in the context of traditional healthcare provider‐directed testing, the risk for incorrect variant curation and interpretation exists. In the absence of deeper investigation into interpretation of such results by an experienced provider (e.g., verification with ClinGen‐informed databases), CGT poses an increased risk for inaccurate variant interpretation and medical management.

Survey results further demonstrated that healthcare providers encountered inappropriate testing in minors using CGT laboratories, a circumstance generally avoided by genetics professionals (Hercher, 2020; National Society of Genetic Counselors, 2018). Despite their relative rarity, these challenges remain important to highlight since parents without access to appropriate counseling may pursue poorly informed testing of their children through CGT (Hasser et al., 2023).

A substantial proportion of respondents, over one‐third (38%), remained undecided about whether potential benefits of CGT outweigh harms. Other surveys have found that only 31.2% of genetic counselors would feel comfortable providing counseling to consumers of DTC testing (Hsieh et al., 2021), highlighting the lack of preparation of even expert genetics providers for navigating the aftereffects of CGT. Interestingly, the current study observed that the more experience a provider had counseling patients based on CGT results, the more they saw benefits of this type of testing. Examples included patients having access to genetic testing who might not otherwise be covered by insurance providers or who might have encountered protracted delays through traditional avenues. One respondent described patients using DTC ancestry testing to find and inform relatives of a clinically confirmed hereditary cancer risk. A prior systematic review identified additional benefits cited by healthcare providers including motivation to lead a healthier lifestyle and be proactive with healthcare, convenience, providing data for research, and increasing genetics knowledge and awareness (Martins et al., 2022). Extant literature also suggests a degree of satisfaction and perceived personal utility of CGT among consumers (Nolan & Ormondroyd, 2023), as well as particular benefits to some individuals including those who are adopted (Lee et al., 2021). While historic concerns about the risks of genetic testing without extensive pre‐test counseling (Andrews et al., 1994) have largely been mitigated by alternative models of genetic testing that provide safety, acceptability, and effectiveness (McCuaig et al., 2018), the importance of embedding post‐test medical guidance in a health care delivery model has also been emphasized (Offit, 2016). In the current survey, more frequent encounters with CGT challenges in general, as well as experience with adverse psychosocial events and incorrect variant interpretation in particular, were associated with increased perceptions of potential harms of CGT outweighing benefits. Because these data were cross‐sectional, it is possible that providers' reports of witnessing patients struggle to make sense of their CGT findings will ameliorate over further time of follow‐up. It is also important to consider that the challenges encountered by genetics providers may differ from those experienced by consumers who may not seek guidance from a provider.

Of the 138 respondents to the exploratory question regarding having previously consulted on circulating tumor DNA test results, 34.1% reported having received this type of referral. This represents a non‐infrequent number of referrals. Given that circulating tumor DNA is an emerging area for future research, this finding indicates there may be opportunity among this study population for further investigation of this topic.

In addition to absence of longitudinal follow‐up, limitations of this report include the use of instruments unvalidated in a prior population, and which by design were directed towards oncology‐focused providers. The focus of the quantitative survey items was on the challenges or concerns providers may have encountered while counseling patients who received CGT. This may have biased their response to the subsequent question that asked whether the benefits of CGT outweigh the potential harms by having them focus on the negative outcomes of CGT. The sampling strategy of distributing the study survey to professional society email lists means that we lack a reliable denominator for how many unique providers actually received the survey invitation; nonetheless, the response rate was low. Thus, the generalizability of findings across disciplines is limited. We additionally did not collect detailed data on providers that would have allowed deeper analysis of associations between provider characteristics and reported outcomes. Quantitative items in our survey also did not fully assess positive experiences with CGT; while the qualitative data obtained here suggest these events are less common, future studies will be required to assess occurrence and correlates of such positive outcomes. Lastly, it is worth noting that we did not differentiate between CGT laboratories that do and do not possess College of American Pathologists (CAP) or Clinical Laboratory Improvement Amendments (CLIA) certifications, or which market laboratory developed tests (LDTs) subject to enforcement discretion by the FDA. It is possible that the reported challenges faced by providers documented here occur more often for a subset of smaller laboratories; however, the current lack of uniform or transparent processes of CMS or FDA to monitor adverse outcomes post LDT, and the current consideration of DTC testing as outside of such enforcement (Food and Drug Administration, 2023), limits such analysis.

5. CONCLUSION

In conclusion, our data suggest that some providers counseling patients who have received CGT encounter substantial challenges including limitations in analytic accuracy, as represented by unconfirmed results and unclear or incorrect variant interpretation, as well as adverse psychosocial effects. Errant interpretation of raw data generated by CGT and run through third party algorithms was a highlighted concern. Additionally, our exploratory data suggest that providers are not infrequently consulting on circulating tumor DNA results. While current practice involves oncologists in the ordering of this type of analysis, anticipatory research on potential patient outcomes is needed as a CGT model may be adopted and issues identified in our data may be relevant for a broader spectrum of healthcare providers. The challenges and risks highlighted here may be mitigated by augmented regulatory oversight of laboratories providing CGT and improved provider and consumer awareness.

AUTHOR CONTRIBUTIONS

Conceptualization: M.T., J.G.H., K.O.; Data curation: M.T., D.G., S.D.; Formal analysis: H.O., J.G.H.; Investigation: M.T., D.G., H.O., A.C., J.G., V.G., S.D., K.B., J.G.H., K.O.; Project administration: M.T., D.G.; Supervision: J.G.H., K.O.; Writing—original draft: M.T., D.G., H.O., J.G.H.; Writing—review and editing: M.T., D.G., H.O., A.C., J.G., C.F., V.G., S.D., K.B., J.G.H., K.O.

FUNDING INFORMATION

This research was supported by NCI P30 CA008748, The Robert and Kate Niehaus Center for Inherited Cancer Genomics, the Andrew Sabin Family Foundation, the Sharon Corzine Foundation, the Breast Cancer Research Foundation, NCI R25CA112486, and NCI CA171998‐11. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Institutes of Health or other funding agencies.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest.

ETHICS STATEMENT

This study was reviewed and approved by the Institutional Review Board of Memorial Sloan Kettering Cancer Center (MSK). The MSK Institutional Review Board approved this study as exempt research; therefore, all respondents confirmed agreement with their voluntary willingness to participate by completing the survey.

Supporting information

Appendix S1.

Trottier, M. , Green, D. , Ovadia, H. , Catchings, A. , Gruberg, J. , Groner, V. , Fanjoy, C. , Dandiker, S. , Blazer, K. , Hamilton, J. G. , & Offit, K. (2024). Genetics healthcare providers' experiences counseling patients with results from consumer genomic testing. Molecular Genetics & Genomic Medicine, 12, e2508. 10.1002/mgg3.2508

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon request.