Trial Information

Proof-of-Principle Trial of Communication to Patients Receiving Predictive Genetic Risk Assessment

The prospect of personalized medicine is under heated debate at the Mayo Clinic and it is of
interest across the world. A point of contention is the provision of individual genetic
risk assessment to healthy patients, especially information predicting risk of common
diseases like diabetes, cancer, or heart disease. While scientific debate continues,
personal genetic testing is currently offered to the public by commercial firms using a
"direct-to-consumer" (DTC) approach. At present, the number of private companies offering
such services is growing (i.e. 23 and me, deCode genetics, etc.). Although many
professionals hope that genetic risk information will prove to be valuable in the near
future, there is little understanding of how this kind of predictive risk assessment will be
interpreted and perceived by patients and their doctors. Due to the great attention given to
predictive genetic testing in the popular press, one expects that patients will soon demand
this testing as part of standard clinical practice. Yet, there is currently no effective
regulatory oversight to guide clinicians and policy makers about how to incorporate results
from predictive genetic testing into routine clinical use. In fact, no appropriate clinical
trials assessing the impact of this type of testing have been completed. Indeed, a recent
commentary in the New England Journal of Medicine recommended that all such testing be
conducted in the context of a clinical trial.

How to protect human subjects during the early stages of development of a new technology is
a classic dilemma in translational research. For that reason, we have developed a
"proof-of-principle" clinical trial at Mayo Clinic to study how patients and their
physicians understand and utilize predictive genetic risk assessment. A critical goal of
this clinical trial is to understand how individual patients and their doctors perceive and
respond to genetic risk information that is largely uncertain.

Our pilot study seeks to answer three fundamental questions: How will physicians deal with
the uncertainty provided by the new technology of predictive genetic risk assessment? What
hopes do patients have regarding the significance of predictive genetic testing? And how do
they interpret their results? This proof-of-principle study will investigate the impact of
direct-to-consumer, predictive genetic testing provided and sponsored by Navigenics, Inc., a
private company advertising predictive genetic testing for common diseases or conditions.
This study will allow Mayo Clinic to be proactive in researching the dynamics of this
potential innovation in health care. The proof-of-principle study described herein is
designed to collect preliminary data that will inform the development of a larger clinical
trial and provide data for an application for federal funding.

Our study will be in collaboration with Navigenics, the industry sponsor of this project.
Navigenics will use a high density, genome microarray for determining the gene variants-,
and published disease-association studies, to calculate the relative risk of each patient
for a few targeted common diseases. High density microarrays are genome chips that allow
the assessment of one million single nucleotide polymorphisms (SNPs) at relatively low cost.
The combination of particular SNPs are presumed to influence the risk of developing certain
common diseases as shown from genome-wide association studies published in peer-reviewed
scientific and medical literature. Navigenics will use these population-based association
studies (studies that produce odds ratios for developing a disease given a certain SNP) to
estimate the relative of an individual patient developing a disease, an approach that is
used by most direct-to-consumer genetic testing companies. They claim that their testing has
a role in preventive medicine in order to "Help people live healthier lives." Our study
will allow us to examine how patients and doctors respond to and utilize Navigenics' risk
assessments derived from microarray technology and published genome-wide association
studies.

The role of information delivery to patients by physicians, genetic counselors or other
health care professionals using predictive genetic risk assessment is unclear. Its
acceptance by patients and health care professionals has also not been studied. Therefore,
this study seeks to compare the perception of genetic risk estimations obtained from
Navigenics' testing with the relative risk estimations obtained through a family history,
the current Mayo standard of care.

Our study design includes two phases to be conducted over 18 months. The first phase is a
"pre-pilot" study that will take place in 2008. In phase one, we will conduct structured
interviews with 20 Executive Health (EH) Program patients who have obtained their disease
risk assessments for common diseases or who have obtained a family history. In phase 2, we
will conduct a quantitative phone survey with 150 EH patients randomized into two arms
(genetic testing and standard of care). We will also conduct follow up qualitative
interviews with 20 patients in phase 2. The study is anticipated to be completed in mid
2009.