Consumer use and response to online third‐party raw DNA interpretation services

Abstract Background With the availability of raw DNA generated from direct‐to‐consumer (DTC) testing companies, there has been a proliferation of third‐party online services that are available to interpret the raw data for both genealogy and/or health purposes. This study examines the current landscape and downstream clinical implications of consumer use of third‐party services. Methods Study participants were recruited online from social media platforms. A total of 321 survey respondents reported using third‐party services for raw DNA interpretation. Results Participants were highly motivated to explore raw DNA for ancestral information (67%), individual health implications (62%), or both (40%). Participants primarily used one of seven companies to interpret raw DNA; 73% used more than one. Company choice was driven by the type of results offered (51%), price (45%), and online reviews (31%). Approximately 30% of participants shared results with a medical provider and 21% shared with more than one. Outcomes of sharing ranged from disinterest/discounting of the information to diagnosis of genetic conditions. Participants were highly satisfied with their decision to analyze raw DNA (M = 4.54/5), yet challenges in understanding interpretation results were reported irrespective of satisfaction ratings. Conclusion Consumers face challenges in understanding the results and may seek out clinical assistance in interpreting their raw DNA results.

SNPedia wiki), that creates personal DNA reports for $5. Other sites offer services to interpret a range of health conditions which vary in price and service (e.g., Genetic Genie, Genomapp, Interpretome, LiveWello).
Following the cease and desist letter from the Food and Drug Administration (FDA) to 23andMe in late 2013, which ordered the company to discontinue marketing of the Personal Genome Service (PGS) and led to the 23andMe's decision to remove health information in their genetic reports, consumers who were interested in health information could seek out third-party online sites to fulfill this need. As such, raw DNA interpretation companies saw a growth in the demand for these services (Bettinger, 2013;Cariaso & Lennon, 2012;Regalado, 2014).
Direct-to-consumer companies such as 23andMe will once again start returning some health risks results following the April 2017 approval of a limited set of health conditions (Food and Drug Administration, 2017). Yet, consumer use of third-party DNA interpretation services will likely continue to grow, particularly with national precision medicine initiatives such as the All of Us Research Program, in which cohort participants are anticipated to have access to their genome sequence data for personal use (Collins & Varmus, 2015;National Institutes of Health, 2017).
Currently, very little is known about how consumers are using raw DNA interpretation services. This study set out to examine the current raw DNA interpretation landscape, assess the impact of these services on consumers, and consider the downstream implications of these services on the health care system.

| Ethical compliance
This study was approved by the Institutional Review Board at Boston University Medical Center, IRB#: H-35096.

| Participants
Study participants were recruited through social media platforms including Facebook, Twitter, and Reddit, between May and June 2016. Paid targeted advertisements for the online survey were used to recruit participants from Facebook and Twitter. Unpaid "posts" advertising the survey were placed on topically relevant subreddits within Reddit (e.g., /r/genetics, /r/ genealogy, /r/23andMe, /r/promethease). All study advertising periods took place over a 10-14-day period.

| Procedures
Participants clicked on the targeted ads or posts and were directed to the study landing page, where they read an online consent statement. Participants who clicked "ok" to agree to participate were then directed to the first question on the survey. Survey topics were informed by other large-scaled studies conducted on DTC testing  and survey items were not intended for the collection of psychometric data on validated psychometric scales. Questions on the survey focused on consumer motivations and decisions to use third-party services to interpret raw DNA including the types of services used, how they learned about the service, and reasons underlying choice of service. In addition, survey items asked the extent to which consumers shared the interpreted results with others, including medical providers, and the outcomes of sharing that information. Satisfaction with choice of service and with the interpreted information was also assessed (see Appendix S1 for survey).

| Analytic plan
Descriptive statistics were used to compute means and standard deviations for continuous variables and counts with percentages for categorical variables. All analyses were conducted using SPSS version 24. Chi-square, linear and logistic regression analyses were performed to examine demographic and psychosocial correlates of (a) sharing of interpreted results with medical professionals, and (b) satisfaction with raw DNA interpretation. Open-ended responses provided within text fields on the survey were reviewed and thematically coded and quantified where appropriate.

| Participant demographics
From the advertising campaign and online posts, a total of 540 individuals provided online consent for the survey and entered the study. Among these individuals, 478 (89%) reported using DTC genetic testing services (e.g., 23andMe, AncestryDNA). Out of those who reported using DTC testing, a total of 321/478 (67%) reported using a third-party service to interpret raw DNA (e.g., Promethease, LiveWello), and thus represent the final sample for the study. Study participants ranged in age from 18 to 81 (M = 46, SD = 15), 68% were female, 82% were White, and 74% were college educated (see Table 1).

| Motivation and decisions to use of online raw DNA interpretation services
Consumers were asked to indicate their motivations to further explore their raw DNA, on a 5-point Likert ranging from "not important at all" (1) to "extremely important" (5); responses were dichotomized into highly important (4 or 5 on scale) versus not. Approximately 67% were highly motivated to explore raw DNA for ancestral information, 62% for individual health implications, 50% due to curiosity about new technology, and 48% for family health implications (see Figure 1). When comparing responses for ancestry and individual health, 40% indicated that information for both was highly important, whereas 28% indicated ancestry motives only, and 22% indicated individual health motives only.

| Health care seeking and sharing behaviors
Consumers were asked about health information seeking and sharing behaviors related to raw DNA interpretation. Only 5% reported seeking advice from a medical practitioner before having raw DNA analyzed by a third-party service and 30% responded either "probably" or "definitely" when asked whether their physician should be responsible for helping them interpret their results. In terms of discussing or sharing results of the raw DNA report with others, 83% reported sharing with family, 62% shared with friends, 30% shared with a medical provider, and 8% shared with others (e.g., online groups, discussion forums, blogs). Among the 96 consumers (out of 321) who shared with a medical provider, 80% shared with a primary care provider, 10% shared with a nurse practitioner, 14% shared with a genetic counselor, and 25% shared with another specialist (e.g., oncologist, ophthalmologist, rheumatologist, naturopathic doctor, psychiatrist, dermatologist, nutritionist). Notably, 21% shared with more than one medical provider.
Sharing of results with medical professionals varied depending on consumers' motives for using third-party interpretation services. Only 9% of consumers with high ancestry information motives (only) shared results with a medical provider, compared to 47% of consumers with high individual health motives only or 42% of consumers who reported both high ancestry and individual health motives (v 2 (3) = 38.4, p < .001). Multiple logistic regression analysis revealed that general health motives, including both individual and family motives, were significant correlates of sharing with medical providers, with higher motives corresponding to greater sharing (Table 2). In addition, those who were more satisfied with the information received from the raw DNA service were also significantly more likely to share results with medical providers.

| Outcomes of sharing raw DNA interpretation results with a medical provider
For participants who reported sharing their results with a medical provider, an open-ended question followed that asked, "What was the outcome of sharing your results with a medical practitioner?" Illustrative quotes from the survey highlighting the outcomes of sharing are provided in Table 3. With primary care providers, approximately 23% of the open-ended comments were related to the lack of discussion of the results due to provider disinterest, lack of understanding of the information, or discounting of results. Consumer responses also reflected interest by some primary care providers and their willingness to learn more about the DNA results presented. Other outcomes related either to discussion of supplements or modifications of medication due to results. In some cases, there was discussion on the implications of DNA test results on medical management including hemochromatosis and breast cancer. Among those who shared with only genetic counselors, outcomes reported included additional clinical testing to verify reports or counseling on results and providing reassurance. Sharing outcomes with other specialists depended on the type of specialist in question. Consumers reported confirmation of various conditions including early agerelated macular degeneration (AMD) and von Willebrand disease (2B), and identification of LHON mitochondrial and BRCA mutations.

| Satisfaction with decision to analyze raw DNA and interpretation results
Consumers were asked about how happy they were with the choice to have their raw DNA analyzed (5-point Likert, higher score reflecting greater happiness). A total of 64% reported 5 out of 5, and 29% reported 4 out of 5 (M = 4.54, SD = 0.72). Open-ended text elaborating on the positive quantitative responses reflected several themes including a) confirmation or explanation of health issues in self or family (e.g., "it confirmed everything that I had already been diagnosed with and allowed me to be aware of which mutations I have in case they ever become activated") and b) identification of health issues not previously suspected (e.g., "The information literally saved my life. I Some consumers also reported being very happy to learn both family and health information due to their adopted status (e.g., "I am adopted [and] it gives me something to go on where I had nothing before." and "I know now more about myself than I ever had in 55 years of living, as a black market adoption, I can finally give some medical info to my children. I really do have relatives!!!").
The majority of consumers reported being very satisfied (34%) or satisfied (47%) with the information they received from the raw DNA interpretation service, whereas 19% were neither unsatisfied or satisfied, unsatisfied, or very unsatisfied. In multiple linear regression analysis, significant correlates of greater satisfaction with information included less education, higher motivation due to curiosity with new technology, and having shared results with a medical provider (Table 2).
When asked to elaborate on their quantitative response, open-ended responses highlighted factors that influenced satisfaction ratings (Table 4). For those consumers who indicated a response other than "very satisfied", qualitative comments primarily reflected confusion and lack of understanding of the reported results, and a lack of resolution to the questions they were seeking answers for.

| DISCUSSION
This study reflects the first attempt to our knowledge to assess the landscape of consumer use of third-party services to interpret raw DNA. The findings from this study shed light into how consumers are finding ways to interpret their genetic data irrespective of the Food and Drug Administration's (FDA) policy regulations. Moreover, although 23andMe was recently granted approval by the FDA to begin returning a subset of health results (Food and Drug Administration, 2017), it is anticipated that consumer demand for raw DNA interpretation will nonetheless increase as a result of the growing availability of genetic data from direct-to-consumer (DTC) testing companies, as well as large-scale research initiatives (e.g., All of Us Research Program, National Institutes of Health, 2017).
Similar to other studies examining DTC personal genetic testing outcomes, consumers are motivated to seek out raw DNA interpretation both for ancestry and health purposes (Roberts & Ostergren, 2013;Roberts et al., 2017). Not surprisingly, consumers whose primary motive was ancestry (only) were significantly less likely to share results with medical professionals. These results add to the prior literature on characteristics of consumers who share results with healthcare providers (Darst, Madlensky, Schork, Topol, & Bloss, 2014;Koeller, Uhlmann, Carere, Green, & Roberts, 2017;van der Wouden et al., 2016). Notably, greater satisfaction with raw DNA information also corresponded to greater sharing of results with medical providers (and vice versa), suggesting that satisfaction and sharing behaviors may be inextricably linked. Further longitudinal research is needed to tease out the direction of the effect.
T A B L E 2 Results of multiple regression analyses examining correlates of (a) sharing results with a medical practitioner and (b) satisfaction with information received from raw DNA interpretation service • Told to ignore the results, and they were likely inaccurate in some way. Informed my results were analyzed in a CLIA lab, and were accurate, only to be told that there wasn't time to sufficiently answer my questions. Insurance declined any use of genetic counselor without additional testing and family history even though I already had raw data. • They said they'd keep it, but didn't feel it was of worth. . . I feel it is a good thing to keep in case you come up with a mystery problem in the future. It helps narrow down potential illness.
Doctor interested, learned from patient, patient-driven care (16/57, 29%) • He found the data interesting but it did not impact my treatment.
• She did not know much about it, but believes DNA analysis is the future.
• Desire to investigate further.
• They learned something.
• The medical practitioner learned something of use to my care, and, the medical practitioner appeared to gain a better understanding of why DTC testing is so useful. • He was interested. Also we were sort of amazed that it foretold many illnesses that I now suffer. Such as an prediction of diabetes, heart problems and arthritis and a possible link to prostate cancer in my future. • She scanned the results for my medical records. We discussed some of my concerns. It was the first time she had ever seen a DNA report.
• Modified type of medication prescribed to fit genomic profile.
• Checked to make sure it was okay to take supplements due to homozygous for MTHFR. Dr said it was and is okay. What I learned about this and other SNPs from Promethease and 23andMe helped explain a lot about my own medical history as well as the past medical history of deceased relatives. It's so interesting. • The most immediate outcome was that it made me realize that the aching in my legs was actually myopathy and a reaction to the statin I was prescribed. We agreed to stop taking the statin and I got better. Consistent with prior literature, approximately 30% of consumers in this study report sharing their raw DNA interpretation results with medical professionals (Darst et al., 2014;van der Wouden et al., 2016). The majority of those who reported sharing with medical professionals shared with a primary care provider (PCP). Responses from PCPs were mixed with approximately 23% lacking interest in the results or dismissing the information. Similar findings related to PCP responses have been reported in other surveys of DTC consumers (van der Wouden et al., 2016). Prior research has demonstrated that PCPs feel they lack the requisite knowledge about DTC testing and feel ill-prepared and challenged to support patients, which may underlie some of the responses noted by consumers (Brett, Metcalfe, Amor, & Halliday, 2012;Carroll et al., 2016;Mainous, Johnson, Chirina, & Baker, 2013;. Additional research on PCP responses when raw DNA interpretation results are shared by patients is warranted.
In this study, over 20% of consumers shared DNA interpretation results with more than one medical professional. The outcomes of sharing with medical professionals reflected, in part, the variation in knowledge and attitudes toward DTC testing across professional disciplines and disease contexts. As such, future studies examining the downstream implications of DNA interpretation on the healthcare system should consider the various professional disciplines that may be impacted, given the likelihood that consumers will share with multiple providers.
Overall, consumers were overwhelmingly happy with their decision to use third-party raw DNA interpretation services. Moreover, 81% reported being very satisfied or satisfied with the interpretation results they received. Yet, consumers also consistently reported challenges with report interpretation irrespective of satisfaction. These challenges are noteworthy and varied across companies to some extent in the open-ended responses provided by consumers. As such, qualitative responses highlight an area of concern with results interpretation and communication that are not Neuro-ophthalmologist • He was intrigued that I found my own LHON mitochondrial mutation by exploring my raw data. He did related testing and was able to figure out why my eyesight had gotten so bad. This disease had been misdiagnosed in relatives for generations as MS or other things. The outcome has been very helpful since now we have access to the correct kind of doctor, testing, information, patient resources, online support group, research studies, etc., since I found my 11778 mutation. It is passed from a mother to all children so this has been very important information for my three children and other maternal relatives. Any doctors I had tried to discuss my genetic results with prior to that, including primary care, ophthalmologist, and geneticist were dismissive and not familiar enough with the testing.

Oncologist
• Not enough information on certain SNP variations to make clinical decisions yet.
Pain therapist • Not much, I feel they don't know what to do with the results yet. But the more people do this, the [sooner doctors] will pay attention.
Multiple practitioners (more than one of those listed above) = 20/96, 21% reflected in the quantitative ratings alone. Not surprising, those who were more highly educated were also less satisfied with the raw DNA information, which may suggest either that their information needs were not met, or that they understood the limitations of the interpretation after receiving the reports thus resulting in lower satisfaction. Additional studies should examine the clarity, informativeness, and comprehension of the interpretation reports communicated by various third-party companies. A strength of this study is the inclusion of quantitative and qualitative analyses pertaining to study outcomes of interest. There are, however, several limitations to this study that should be noted. This study recruited participants via social media through paid advertisements (Facebook/ Twitter) and posts on relevant discussion threads (Reddit) and may favor attracting consumers who had more favorable experiences or are high information seekers who may be likely to use more than one third-party service and share results with multiple health professionals. As such, generalizability of findings may be limited to some extent by the potential selection bias in sampling.

MD, GC
In addition, openended responses were not required of all study participants on the survey and thus likely understate the context and detail of the outcomes of sharing with medical • I feel there is a lot of good information but I'm still feeling overwhelmed and a bit unclear about some of how some of the tools work and how they would help me. • Some of the services could improve their reporting clarity but the core services are helpful. • It's a bit hard to follow and some things contradict other things (e.g., One gene shows I should have brown eyes, another shows I should have blue. I actually have blue.) • While they gave me a lot of good information, there was so much of it because of the number of variants I had, and it was presented in a way that was not easily accessible for even a well-educated layperson. I ended up paying a dietitian to look at the raw data and write up a report for me, which she did for a reasonable fee. I then sat down with one of her colleagues and discussed what it meant for me in real life.
Neither 14% • Better tools needed. • More confused than ever.
• The interface is a bit unfriendly and difficult to use. • I haven't been able to use it for answers.
• I don't understand the information.
• Difficult to understand everything.
• Still don't completely understand some of the information.
• They provided lots of information but it was beyond me to organize and interpret it myself.
• I think interfaces could be a little better, make it easier for the user.
• It's a lot like astrology for the most part. I worry that most laypeople are going to be overinterpreting this stuff. Nevertheless, extremely enjoyable to explore. • Too much complex info & terms, not enough general explanation for the layman.
Unsatisfied or very unsatisfied 5% • I am frustrated that the raw DNA data is incomplete and politically filtered.
• It was not a complete report.
• Still a lot of technical data that is hard to decipher.
• Much of it is very limited and scattershot.
practitioners. Additional efforts are needed to examine the utility and impact of sharing DTC testing results with these professionals.
In sum, consumers are overwhelmingly satisfied with their decision to use third-party raw DNA interpretation services, in spite of the challenges with understanding interpretation results. Future efforts to ascertain consumer comprehension of interpretation results and subsequent interactions with medical professionals will facilitate a better understanding of the downstream implications of these online services.