Heart and Blood Diseases

Symptoms and General Pathology

All Conditions

Nutritional and Metabolic Diseases

Neoplasms

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Musculoskeletal Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Eye Diseases

Immune System Diseases

Digestive System Diseases

Myocardial Infarction

Infarction

Obesity

Breast Neoplasms

Diabetes Mellitus

Diabetes Mellitus, Type 2

Osteoarthritis

Prostatic Neoplasms

Lung Neoplasms

Atrial Fibrillation

Graves Disease

Celiac Disease

Arrhythmias, Cardiac

Heart Diseases

Ischemia

Necrosis

Coronary Artery Disease

Myocardial Ischemia

Vascular Diseases

Gastrointestinal Diseases

Intestinal Diseases

Syndrome

Malabsorption Syndromes

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Exophthalmos

Orbital Diseases

Goiter

Thyroid Diseases

Hyperthyroidism

Autoimmune Diseases

Those who will receive predictive genetic risk assessments

The patients in the intervention group will obtain genetic risk assessments based on genome-wide association studies.

SNP analysis

Kristina Tiedje, Ph.D.

Clayton T. Cowl, M.D.

Barbara A. Koenig, Ph.D.

This proof-of-principle clinical trial at Mayo Clinic studies 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.

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.

Predictive Genetic Risk Assessment Trial

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

Mayo Clinic

We will use a prospective, observational cohort design, we will invite a sample of individuals who have indicated willingness to be re-contacted for future studies (from existing protocols involving cancer survivors and their unaffected relatives employing mixed methods -qualitative interviews coupled with validated measures - to assess: the proportion of participants experiencing psychological distress from Whole genome/exome sequencing (WGS/WES) results.

We will also recruit an additional group of participants from the general public (with or without a cancer history) who have not had their genomes or exomes sequenced to participate in focus groups to inform us about their perceptions of the hypothetical utility of learning of incidental results from their genome or exomes. For our sampling purposes, this group of participants is referred to as the 'focus group participants (sample #3-hypothetical group)

A week before the participants return to the clinic to learn of their results, the RSA will call each participant to complete the Hospital Anxiety \& Depression Scale (HADS), revised Impact of Events Scale (IES-R), \& a questionnaire about their health behaviors, to establish baseline distress levels \& health behaviors. A week later, participants will return to the Clinical Genetics Service to review their results with the genetics provider \& discuss resultant therapeutic \& management recommendations for the participants \& their relatives. A week later, the RSA will call each participant to complete the HADS, IES-R again, to establish the safety of receiving these results. Participants will also be asked to complete the revised Multidimensional Impact of Cancer Risk Assessment (MICRA) measure. The RSA will also invite participants to complete an in-depth telephone interview.

qualitative interviews

Mark Robson, MD

This study uses new methods called "genome sequencing" that allow the investigators to study part or all of a person's genome. The genome is the collection of all of a person's genes. Genes carry the instructions that our bodies need to develop and function. Genes are passed on from one generation to the next. Genome sequencing can study all of a person's genome (whole genome sequencing) or just parts of their genome (whole exome sequencing). In the study, the investigators refer to all these research methods as 'genome sequencing'. Genome sequencing typically shows a large number of gene changes, known as "variants." Some (but not all) of these genetic variants may be linked to increased risks of diseases other than cancer.

The purpose of this study is to learn what kinds of genetic variants the patient wants to learn about from their genome.

Participants will be recruited from cohorts of patients whose DNA samples are being examined with WGS/WES as part of efforts to identify novel cancer susceptibility alleles. Participants will be derived from the following protocols: 09-068 and 96-051.

A Safety Study Assessing the Effects of Receiving Genome Sequencing Results

Personal Genomics: A Safety Study Assessing the Effects of Receiving Genome Sequencing Results

of receiving incidentally identified disease risk results from whole genome/exome sequencing. Safety is defined as no more than 20% of participants experiencing clinically meaningful levels of distress at 1 week follow-up, as measured by the Hospital Anxiety \& Depression Scale (HADS; score \> or = to 8 on the anxiety sub-scale). Patients will be considered evaluable for the primary outcome if they are not distressed at baseline and have completed the 1 week follow-up assessment.

Memorial Sloan Kettering Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Predictive Genetic Risk Assessment Trial	NCT00782366	Colon Cancer Lung Cancer Atrial Fibrilla... Diabetes Type 2 Obesity Breast Cancer Graves Disease Osteoarthritis Celiac Disease Myocardial Infa... Prostate Cancer	SNP analysis	18 Years - 65 Years	Mayo Clinic
A Safety Study Assessing the Effects of Receiving Genome Sequencing Results	NCT01692223	History of Canc...	qualitative int...	18 Years -	Memorial Sloan Kettering Cancer Center
Predictive Genetic Risk Assessment Trial	NCT00782366	Colon Cancer Lung Cancer Atrial Fibrilla... Diabetes Type 2 Obesity Breast Cancer Graves Disease Osteoarthritis Celiac Disease Myocardial Infa... Prostate Cancer	SNP analysis	18 Years - 65 Years	Mayo Clinic

Spots Global Cancer Trial Database for personal genomics