Evaluation of self-mediated alternatives for risk testing education and return of results (eSMARTER) study: A randomized study of methods for returning APOE and pTau-217 results

INTRODUCTION: Disclosing Alzheimer's disease (AD) genetic and biomarker information is becoming increasingly common but often resource-intensive, requiring a clinician to return results. As results become relevant for clinical care and more people want to learn their results, scalable approaches to disclosure are needed. Here, we describe the design of a decentralized, randomized, non-inferiority clinical trial (eSMARTER) to evaluate self-directed scalable digital methods for returning APOE and plasma pTau-217 results. METHODS: Participants (n ≈ 600) aged 60–80 years are randomized to receive their apolipoprotein E (APOE) and pTau-217 results via either a clinician-mediated telehealth videoconference (usual care) or a self-mediated eHealth platform. The primary hypothesis is that self-mediated APOE disclosure will result in non-inferior outcomes compared to clinician-mediated disclosure. The three primary outcomes are changes in anxiety, AD-related knowledge, and disease-specific distress. For the three primary analyses, we will apply non-inferiority tests to examine if self-mediated disclosure provides equivalent or improved outcomes compared to usual care. Our secondary hypothesis is that learning APOE and pTau-217 results will affect participants’ mood, self-perception of disease risk, and quality of life. We hypothesize participants who learn results indicating more risk will report increased, but not clinically significant psychological distress and increased disease risk. We hypothesize there will not be changes in quality of life. We will examine change scores of the validated mood, self-perception of disease risk, and quality of life measures from pre- to post-disclosure. RESULTS: Data collection is ongoing. Results will allow for non-inferiority comparisons between clinician- and self-mediated disclosure of APOE results and initial characterization of the impact of learning pTau-217 results. DISCUSSION: The eSMARTER Study represents an important step towards meeting expected increases in demand for learning AD genetic and biomarker information. The digital platforms developed for this study will be made available to support clinicians and investigators returning genetic and/or biomarker results. Highlights: Novel, scalable design for self-mediated disclosure of APOE and pTau-217. Non-inferiority trial examining self-mediated versus clinician-mediated disclosure. All materials, methods, data, and samples will be shared publicly.