Designing and Executing a Gene Testing Counseling and Disclosure Process

In our world of clinical trials, disclosure of a person’s genetic susceptibility to major diseases such as Alzheimer’s is not only a potentially life-changing experience for the person and their family, but is also becoming a critical component for the design and development of countless future research trials for many diseases.

Genetic testing and disclosure has become particularly crucial for us because the Alzheimer’s research paradigm is shifting, with scientists now focusing their efforts on identifying high-risk individuals prior to clinical onset of the disease. Our genetic disclosure program is helping us further study the impact of learning about a genetic risk factor for a disease that currently has no treatment or cure. And we have developed a testing and disclosure model that appears to be working effectively in dealing with this complex challenge.

As part of the Alzheimer’s Prevention Initiative (API) Generation Program, we are identifying cognitively healthy individuals ages 60-75 who are at high risk of developing symptoms of Alzheimer’s because of their age and because they carry either one or two copies of the e4 type of the apolipoprotein E (APOE) gene, the major genetic risk factor for late-onset Alzheimer’s disease.

Because our prospective participants are required to learn their APOE genetic test results, we developed the API Genetic Counseling and Disclosure Process (GCDP) to determine the most efficient and effective way to incorporate both genetic counseling and disclosure into the screening process to maximize potential participants’ psychological readiness to receive results prior to disclosure of APOE genotype.

Results from an earlier study, Risk Evaluation and Education for Alzheimer’s Disease (REVEAL), published in The New England Journal of Medicine, showed us that the disclosure of APOE results was generally safe and did not trigger short-term psychological risks. However, there are two important distinctions between REVEAL and the Generation Program:

• Participants in the REVEAL study were younger than those in the Generation Program, thus making them further away from their age of risk, and years away from their chances of developing Alzheimer’s.

• The REVEAL study included a smaller number of people with two copies of the e4 type of the APOE gene.

A traditional genetic counseling and disclosure model consists of multiple in-person visits, including a pre-testing educational counseling session, a testing component which can sometimes be combined with the first visit, and a post-testing counseling refresher and disclosure. However, for the Generation Program, we needed to design a process for counseling and disclosure that could be implemented in the context of our trials and could be adaptable and scalable for implementation across numerous sites in various countries. In addition, they needed to be based on varying local laws and regulations, differing referral sources, and varying degrees of knowledge among participants about their genetic vulnerability.

We use a modified design of the traditional genetic counseling and disclosure model to streamline the screening process, including three main components:

• A pre-disclosure educational video and an educational handout that are typically included in a pre-testing educational counseling session and that inform participants about Alzheimer’s, APOE, and considerations for learning their APOE results. These materials are available to prospective study volunteers prior to deciding whether to participate in the Generation Program.

• APOE testing via a cheek swab to assess a potential participant’s genetic risk for the disease. (Note: some participants have already provided a sample through GeneMatch, a program that matches healthy volunteers to Alzheimer’s prevention studies based in part on their genetic profile, or through direct-to-consumer genetic testing. But if not, a sample is collected as part of the study.)

• A counseling and disclosure visit that is completed remotely using telegenetics or through a local provider. 

To assist in clearly and safely communicating genetic information, a risk-disclosure handout, guided talking points, and genotype-specific summary sheets are used as part of the disclosure process. Participants are also assessed in terms of their level of genetic knowledge, psychological wellbeing, health behaviors, impact of disclosure, and satisfaction with disclosure at multiple time-points following the disclosure session to examine the ongoing impact of learning their APOE results.

Given the number of study sites and the limited availability of genetic counselors, we knew it was not possible to have all potential participants meet face-to-face with counselors to learn their genetic information. Therefore, we incorporated an ancillary sub-study-CONNECT 4 APOE-which utilizes telemedicine to deliver testing results either via telephone or videoconference. Through this effort, we are comparing the tolerability of each method to inform our program and future research efforts with the goal of helping to inform the development of scalable delivery models in the future, as well as insight toward the clinical implementation of APOE genetic testing for Alzheimer’s disease risk assessment.

Many providers and study sites in the U.S. and around the world do not have experience with disclosure of APOE results, so the API GCDP provides an effective method for structuring genetic counseling and disclosure and for facilitating clear and consistent communication of genetic information in global clinical trials. Generation Program study sites have expressed high satisfaction and appreciation for the GCDP. We are gaining valuable information about how to effectively and efficiently disclose genetic information and how to make this process adaptable for studies with varying populations and country involvement. The information we are collecting will allow for ongoing refinement and improvement of the API GCDP for design of genetic disclosure in future studies.

Jessica Langbaum, PhD, is Principal Scientist at Banner Alzheimer’s Institute and Associate Director of the Alzheimer’s Prevention Initiative.