Using Direct-to-Consumer Genetic Testing Results in Alzheimer’s Disease Clinical Trial Recruitment

Abstract

The apolipoprotein E (APOE) gene is the best described genetic risk factor for Alzheimer’s disease (AD). Carriage of one or two copies of the ε4 allele of APOE indicates increased risk for AD. Given that APOE ε4 carriage is associated with preclinical AD in older populations, APOE genotype can be used to enrich preclinical AD trials. Other trials are underway that exclusively enroll specific APOE genotypes. In 2017, the Food and Drug Administration granted 23andMe permission to market 10 disease-risk genetic tests direct-to-consumers (DTC), including APOE. With DTC genetic testing available to the public, participants may enter studies with personal knowledge of their APOE genotype. Researchers could use this personal knowledge to pre-enrich preclinical AD trials, were participants willing to share this knowledge with investigators. Little is known, however, about potential study participants’ willingness to disclose their personal genetic information gained though DTC testing. Improved understanding of participant attitudes could instruct intervention to improve trial recruitment, including recruitment of underserved populations. We sought to quantify the relationship between participant characteristics and whether a participant has used DTC genetic testing. We hypothesized that non-White participants would be less likely to have used DTC testing than their non-Hispanic White counterparts. We also sought to assess the relationship between participants’ use or non-use of DTC genetic services and their willingness to use DTC results to be matched to clinical studies. Finally, we sought to assess differences in reasons for reluctance to share genetic results, comparing DTC users and non-users. Links to a survey were emailed to 2,306 members of the University of California, Irvine Consent-to-Contact (C2C) Registry who were at least 50 years of age or older. The age restriction for this analysis was implemented to reflect inclusion criteria for AD trials. In total, 1,313 valid responses were recorded. Branching logic was used to examine participants’ awareness and previous use of DTC services, willingness to learn their APOE status, and willingness to share genetic information with researchers. Specific questions queried participants’ desires for researchers to use genetic test results to match them to studies and reasons for reluctance to permit this. Survey responses were linked to demographic information available in the C2C Registry. We used logistic regression models to assess the relationship between previous use of DTC testing and race/ethnicity, as well as the relationship between previous use of DTC testing and willingness to use the results of DTC testing for invitation to clinical studies. We also used a logistic regression model to assess the relationship between previous use of DTC testing and reasons for reluctance to share genetic results. Participant age, years of education, and sex were adjusted for in all models as potential confounding variables. In addition, race/ethnicity and APOE carrier status were adjusted for in the latter two models. Most survey participants were aware of DTC genetic testing (N=1,016, 77.44%), while few had used such a test prior to the survey (N=91, 6.93%). Among those undergoing testing, 27 (29.67%) identified themselves as APOE ε4 carriers. Most participants who knew their APOE status from DTC tests were willing to share those results in their C2C Registry profile (N=77, 84.61%). Participants who identified as American Indian/Alaska Native (OR 0.13; 95% CI 0.01, 2.93) or Asian (OR 0.08; 95% CI 0.01, 0.71) were less likely to be users of DTC genetic tests, compared to non-Hispanic Whites. Participants who had used DTC genetic tests were more likely to be willing to include their APOE status in their registry profile, compared to non-users (OR 1.28; 95% CI0.11, 14.68). DTC users who were APOE ε4 carriers were more likely to be willing to include their APOE status than DTC users who were non-carriers (OR 3.45; 95% CI0.37, 32.34). Finally, out of the 37 participants who indicated they would be unwilling to share their APOE genotyping results in the registry, most were concerned about implications to their insurance (N=16; 43.24%) and implications to their healthcare (N=13; 35.14%). Previous DTC users are more willing to share their results for clinical trial matching, compared to non-users. This may indicate that hypothetical responses about willingness to share genetic information with investigators may be underestimates. Alternatively, those most willing to share their results may also be those most likely to use DTC testing.

Mary M. Ryan

Assistant Professor
mary [dot] ryan [at] wisc [dot] edu

My research interests include group sequential design and clinical trials, with applications in Alzheimer’s Disease biomarker discovery, as well as pragmatic and cluster randomized trials.