In keeping with this phased research approach, in the spring of 2006 we launched the Multiplex Initiative, a pre-clinical phase research project with two overarching aims. The first aim was to gain information from a population-based sample of adults (i.e., a sampling frame with a known denominator) about who, when offered genetic susceptibility testing for common health conditions, would be interested in being tested and to explore behavioral responses to test results among those who opted for testing. Specific questions that are being addressed through the Multiplex Initiative include examining whether there are social and psychological differences between those who opt to be tested versus those who decline testing, whether individuals who opt for such testing are able to accurately interpret their test results, whether these individuals' interpretation of their test results is associated with positive or negative emotions or changes in their perceptions about their personal risk for health conditions, and whether receiving their results lead them to seek other personal risk information, either through conversations with health care providers or other means (e.g., family history and behavioral risk assessments). Answering the questions posed above required us to develop at test battery, a standardized approach for offering the test that enabled informed decision-making and provided feedback in a form that could ultimately be applied in a public health setting.
Initial planning for the Multiplex Initiative involved a year's worth of working group meetings with a trans-disciplinary team of scientists who advised us on “best practices” for the prototype test development, methods for obtaining informed decision-making and research consent, and risk feedback approaches. One outcome of this process was the development and deployment of a multiplex genetic susceptibility test prototype for 15 genetic polymorphisms associated with increased risk for eight common health conditions. The health conditions were carefully selected, with consideration given to evaluating the primary prevention potential of genetic susceptibility testing for these conditions. Thus, we selected health conditions (type 2 diabetes, lung, colon, and skin cancer; heart disease, hypercholesterolemia, high blood pressure, and osteoporosis) that are adult-onset and “preventable” – meaning that there are widely accepted prevention recommendations for reducing individual risk for these conditions. Our study subjects are healthy adults ages 25−40 who are all members of the Health Alliance Plan and the Henry Ford Medical Group (both of which are part of a large non-profit health care organization). We decided to conduct this research with an insured population to address our concerns that study participants receiving risk feedback have ready access to prevention services and to enable assessment of patterns of health care use.
Study participants can review in-depth information regarding the testing via a secure Web portal (http://multiplex.nih.gov
). Those who opt for testing receive additional study-related information during their clinic visit for blood collection. Tested individuals receive their results, along with a report explaining the meaning of their results, in the mail about six months after blood collection. They then receive a telephone call from a research educator who further explains their results and answers any questions the participant may have. Study participants are re-contacted three months after receiving their test results for a follow-up telephone survey.
The Multiplex Initiative represents a modest first step, but will answer basic questions related to comparisons of individuals who do and do not opt for genetic susceptibility testing. This initiative also will provide the first population-based insight into who is most likely to be among the early adopters of genetic susceptibility testing. Since we are surveying and offering testing to a large and diverse sample of individuals, many of whom will not seek testing, we will have a good deal of information on which we can compare those who do and do not get tested. Additionally, the Web interface will enable us to evaluate an individual's responses to information about genetic susceptibility in real time. This will provide insight into the elements of the information presented that most and least influenced individual's decisions to undergo genetic susceptibility testing. The telephone conversations between participants and research educators to discuss their test results also will lend insight into what individuals perceive to be the take-home messages from their test feedback. For example, are they able to understand caveats about the substantial and greater importance of their behaviors above that of their genotypes as contributors to health conditions? Lastly, our considered choice of shorter- over longer-term behavioral outcomes enables us to gain insight into best practices for conveying to individuals the limits and uncertainties of personalized genetic susceptibility test feedback for common health conditions. At this early stage, it is critical to gain insight into the immediate consequences of genetic susceptibility feedback (both positive and negative) on participants' perception of their own personal risk. This can be measured by observing the participants' actions taken after multiplex testing for example their seeking a more complete picture of their personal disease risk (e.g., completion of family history tools, completing behavioral self-assessments, or engaging in conversations with health care providers and other family members).
Recruitment for the Multiplex Initiative began early in 2007. We have approached over 4000 individuals to date, with the goal of accruing 500 who receive the multiplex genetic test. Currently, we have completed over 2000 baseline surveys designed to gather information on how these individuals seek out health information, their beliefs about the role of genetics and behavior in the cause of common health conditions, and their perceptions about their own health. Although recruitment is still underway, preliminary results indicate that, for most, their participation in the Multiplex Initiative is their first experience with clinical research. The majority of individuals who have completed the baseline survey are high school graduates, married, self-report being in excellent or good health, and are relatively familiar with their family's health history. To date, 44% of participants are male and 30% are African-American, which is roughly proportional to the patient population from which the sample was drawn. So far, over 500 individuals have visited the study's Web site to consider testing; to date, about 300 have decided to undergo testing.
The Multiplex Initiative is still in its recruitment phase, so we cannot yet report outcomes. Initial observations by the research educators who have reviewed test feedback reports with the first 50 participants indicate that recipients are not reporting high anxiety about their test results. However, we do not yet have the nuanced understanding of participants' responses that ultimately will be gained from the detailed information we are collecting at each step in the project. We have amassed a comprehensive data set that will enable us to investigate which factors may discriminate the 1500 or more individuals who never logged onto the Web site to consider testing from the 500 who did and, in turn, from the even smaller group that requested testing. Accordingly, we believe that the results of the Multiplex Initiative will provide us with an initial step towards understanding whether healthy individuals use genetic susceptibility testing in ways that could benefit their health.