Comparing Self-Referred and Systematically Recruited Participants in Genetic Susceptibility Testing Research: Implications for Uptake and Responses to Results.

Studies examining whether genetic susceptibility testing for common, complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results. An understudied area that may help reconcile these differential findings involves how testing was initiated. The overall goal of this dissertation was to understand the implications of different sampling strategies by examining self-referred versus systematically recruited populations in genetic susceptibility testing research. Using data from the Risk Evaluation and Education for Alzheimer’s Disease (REVEAL) Study, a series of randomized controlled trials exploring genetic susceptibility testing for Alzheimer’s disease (AD), I compared self-referred and systematically recruited participants in a series of secondary analyses organized into three papers. Paper 1 compared the profiles of self-referred and systematically recruited participants at enrollment, finding demographic differences (e.g., fewer African Americans and greater household incomes in the self-referred cohort), and greater AD worry among self-referred participants. Cohorts did not differ on beliefs about the benefits, risks and limitations of testing, perceptions about susceptibility, severity, causes, or controllability of AD, or self-efficacy about coping, however. Paper 2 examined responses to pretest education, finding self-referred participants more likely to learn that testing was not deterministic. Analyses of test uptake found self-referred participants more likely to retain through the initial steps of the study, but no cohort differences beyond the education phase. Paper 3 examined changes to advance planning and health behaviors after testing, finding that self-referred participants with higher-risk results were more likely than their systematically recruited counterparts to report or plan changes to long-term care insurance, mental activities, diet and exercise. Self-referred participants at increased risk also reported greater uncertainty about testing results. The two groups did not differ in post-test reports of distress or positive experiences, however, or on changes to perceptions of AD susceptibility and concern. Findings suggest that individuals proactively seeking genetic susceptibility testing for common, complex diseases are more likely to follow through with testing and use it to inform behavior changes than those who are approached by others. These results highlight the challenge of generalizing findings derived from research on self-referred populations to the population at-large.PHDHealth Behavior And Health EducationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/94095/1/kdchrist_1.pd

O3‐02‐01: Direct‐To‐Consumer Genetic Testing For Risk Of Alzheimer’S Disease (Ad): The Psychological And Behavioral Impact Of Apoe Genotype Disclosure

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153046/1/alzjjalz201404274.pd

O3‐02‐06: What Is The Long‐Term Emotional And Behavioral Impact Of Genetic Risk Assessment For Alzheimer’S Disease? Findings From The Reveal Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153033/1/alzjjalz201404279.pd

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used