Burden or benefit? Effects of providing education about and the option to request additional genomic findings from diagnostic exome sequencing: A randomized controlled trial.

OBJECTIVE: Many people prefer to learn secondary or "additional" findings from genomic sequencing, including findings with limited medical actionability. Research has investigated preferences for and effects of learning such findings, but not psychosocial and behavioral effects of receiving education about them and the option to request them, which could be burdensome or beneficial (e.g., causing choice overload or satisfying strong preferences, respectively). METHODS: 335 adults with suspected genetic disorders who had diagnostic exome sequencing in a research study and were randomized to receive either diagnostic findings only (DF; n = 171) or diagnostic findings plus education about additional genomic findings and the option to request them (DF + EAF; n = 164). Assessments occurred after enrollment (Time 1), after return of diagnostic results and-for DF + EAF-the education under investigation (Time 2), and three and six months later (Times 3, 4). RESULTS: Time 2 test-related distress, test-related uncertainty, and generalized anxiety were lower in the DF + EAF group (ps = 0.025-0.043). There were no other differences. CONCLUSIONS: Findings show limited benefits and no harms of providing education about and the option to learn additional findings with limited medical actionability. PRACTICE IMPLICATIONS: Findings can inform recommendations for returning additional findings from genomic sequencing (e.g., to research participants or after commercial testing).

Factors influencing NCGENES research participants' requests for non-medically actionable secondary findings.

PURPOSE: Genomic sequencing can reveal variants with limited to no medical actionability. Previous research has assessed individuals' intentions to learn this information, but few report the decisions they made and why. METHODS: The North Carolina Clinical Genomic Evaluation by Next Generation Exome Sequencing (NCGENES) project evaluated adult patients randomized to learn up to six types of non-medically actionable secondary findings (NMASF). We previously found that most participants intended to request NMASF and intentions were strongly predicted by anticipated regret. Here we examine discrepancies between intentions and decisions to request NMASF, hypothesizing that anticipated regret would predict requests but that this association would be mediated by participants' intentions. RESULTS: Of the 76% who expressed intentions to learn results, only 42% made one or more requests. Overall, only 32% of the 155 eligible participants requested NMASF. Analyses support a plausible causal link between anticipated regret, intentions, and requests. CONCLUSIONS: The discordance between participants' expressed intentions and their actions provides insight into factors that influence patients' preferences for genomic information that has little to no actionability. These findings have implications for the timing and methods of eliciting preferences for NMASF and suggest that decisions to learn this information have cognitive and emotional components.

The who, what, and why of research participants' intentions to request a broad range of secondary findings in a diagnostic genomic sequencing study.

PURPOSE: In a diagnostic exome sequencing study (the North Carolina Clinical Genomic Evaluation by Next-Generation Exome Sequencing project, NCGENES), we investigated adult patients' intentions to request six categories of secondary findings (SFs) with low or no medical actionability and correlates of their intentions. METHODS: At enrollment, eligible participants (n = 152) completed measures assessing their sociodemographic, clinical, and literacy-related characteristics. Prior to and during an in-person diagnostic result disclosure visit, they received education about categories of SFs they could request. Immediately after receiving education at the visit, participants completed measures of intention to learn SFs, interest in each category, and anticipated regret for learning and not learning each category. RESULTS: Seventy-eight percent of participants intended to learn at least some SFs. Logistic regressions examined their intention to learn any or all of these findings (versus none) and interest in each of the six individual categories (yes/no). Results revealed little association between intentions and sociodemographic, clinical, or literacy-related factors. Across outcomes, participants who anticipated regret for learning SFs reported weaker intention to learn them (odds ratios (ORs) from 0.47 to 0.71), and participants who anticipated regret for not learning these findings reported stronger intention to learn them (OR 1.61-2.22). CONCLUSION: Intentions to request SFs with low or no medical actionability may be strongly influenced by participants' desire to avoid regret.

Development and Validation of a Genomic Knowledge Scale to Advance Informed Decision Making Research in Genomic Sequencing.

BACKGROUND: This study evaluated the psychometric properties of a new, comprehensive measure of knowledge about genomic sequencing, the University of North Carolina Genomic Knowledge Scale (UNC-GKS). METHODS: The UNC-GKS assesses knowledge in four domains thought to be critical for informed decision making about genomic sequencing. The scale was validated using classical test theory and item response theory in 286 adult patients and 132 parents of pediatric patients undergoing diagnostic whole exome sequencing (WES) in the NCGENES study. RESULTS: The UNC-GKS assessed a single underlying construct (genomic knowledge) with good internal reliability (Cronbach's alpha = 0.90). Scores were most informative (able to discriminate between individuals with different levels of genomic knowledge) at one standard deviation above the scale mean or lower, a range that included most participants. Convergent validity was supported by associations with health literacy and numeracy (rs=0.41-0.46). The scale functioned well across subgroups differing in sex, race/ethnicity, education, and English proficiency. DISCUSSION: Findings supported the promise of the UNC-GKS as a valid and reliable measure of genomic knowledge among people facing complex decisions about WES and comparable sequencing methods. It is neither disease- nor population-specific, and it functioned well across important subgroups, making it usable in diverse populations.

Understanding self-management behaviors in symptomatic adults with uncertain etiology using an illness perceptions framework.

The self-management behaviors of individuals with medical conditions that have an unknown etiology have not been studied. This study assesses the relationship between illness perceptions and various illness self-management behaviors in patients undergoing clinical genomic sequencing to identify a genetic cause for their condition. Hierarchical linear regression, Poisson linear regression, and logistic regression were used to assess the effect of illness perceptions (i.e., perceived consequences, timeline, personal control, treatment control, identity, concern, understanding, emotional impact, and causal beliefs as measured by the Brief Illness Perceptions Questionnaire) on healthcare use, prescription medication use, and doctor recommended supplement use, respectively (n = 200). Analyses revealed that (1) illness identity beliefs were positively associated with healthcare use (ß = 0.20, p = 0.04), (2) both treatment control beliefs (B = 0.03, p = 0.02) and genetic causal beliefs (B = 0.17, p = 0.049) were positively associated with prescription medication use, and (3) both timeline beliefs (OR 1.23, p = 0.02) and emotional impact (OR 1.20, p = 0.02) were positively associated with doctor recommended supplement use. These findings can be used to inform the development of guidelines for treating patients who are seeking a genetic diagnosis for their illness.

Patient hopes for diagnostic genomic sequencing: roles of uncertainty and social status.

For patients with unexplained or undiagnosed conditions, genomic sequencing offers the hope of resolving unanswered questions. With the growth of clinical genomic sequencing, understanding factors that shape patients' hope for information could have important implications for developing patient education guidelines. Based on the goal-directed theory of hope, we investigated illness uncertainty as a form of motivation and subjective social status as a form of perceived resources to predict the amount and kinds of information that adult patients (N=191) and parents of pediatric patients (N=79) hoped to receive from diagnostic sequencing results. Participants were part of a larger longitudinal study on clinical genomic sequencing, but the current study focuses on their hopes for diagnostic sequencing results. Hopes for information were assessed through close-ended and open-ended responses. Findings from mixed methods analyses indicated that although patients and parents hoped to learn multiple kinds of information from diagnostic sequencing results, their hopes appeared to be influenced by their illness uncertainty and perceptions of their social and economic resources. These findings suggest that patients' illness uncertainty and perceived resources could be useful avenues for discussing patient hopes and educating patients about strengths and limitations of genomic sequencing.

How can psychological science inform research about genetic counseling for clinical genomic sequencing?

Next generation genomic sequencing technologies (including whole genome or whole exome sequencing) are being increasingly applied to clinical care. Yet, the breadth and complexity of sequencing information raise questions about how best to communicate and return sequencing information to patients and families in ways that facilitate comprehension and optimal health decisions. Obtaining answers to such questions will require multidisciplinary research. In this paper, we focus on how psychological science research can address questions related to clinical genomic sequencing by explaining emotional, cognitive, and behavioral processes in response to different types of genomic sequencing information (e.g., diagnostic results and incidental findings). We highlight examples of psychological science that can be applied to genetic counseling research to inform the following questions: (1) What factors influence patients' and providers' informational needs for developing an accurate understanding of what genomic sequencing results do and do not mean?; (2) How and by whom should genomic sequencing results be communicated to patients and their family members?; and (3) How do patients and their families respond to uncertainties related to genomic information?

Erratum to: How can psychological science inform research about genetic counseling for clinical genomic sequencing?

Erratum to: J Genet Counsel DOI 10.1007/s10897-014-9804-6. Grant support from the Clinical Sequencing Exploratory Research program of the National Human Genome Research Institute was awarded to James P. Evans, Jonathan S. Berg, and Gail E. Henderson for the NCGENES Study (NIH #U01 HG006487). The authors and publisher regret the omission from the original article.

Influences of spousal support and control on diabetes management through physical activity.

OBJECTIVES: Spouses may be involved in their partner's diabetes management by providing social support to affirm healthy behaviors and social control to modify health behaviors. Yet, investigations of the influence of spousal involvement on daily patient health behaviors are limited. In daily diaries, we investigated how spousal support and control independently and jointly influence patient physical activity and efficacy to engage in physical exercise on a daily basis. METHODS: Older adults (age 55 and older) with Type 2 diabetes and their spouses (N = 70 couples) completed electronic diaries for seven consecutive days that assessed spouse-reported involvement and patient-reported minutes of physical exercise and efficacy to engage in future physical exercise. A subset of patients (N = 53) also wore an activity monitoring device on the wrist that provided a measure of energy expenditure. RESULTS: Multilevel analyses indicated that on a daily basis, spousal support was positively associated with physical activity, whereas spousal control was either unrelated or linked to less physical activity. On days in which spouses provided high levels of both support and control, however, patients felt more efficacious that day about exercising tomorrow and exhibited an increase in energy expenditure on the next day. CONCLUSIONS: Findings suggest that spousal exercise support on its own or in conjunction with spousal exercise control may facilitate daily diabetes management through physical activity.

Spousal support following knee surgery: roles of self-efficacy and perceived emotional responsiveness.

OBJECTIVE: The objective was to investigate self-efficacy to manage recovery from surgery and perceptions of the spouse's emotional responsiveness of adults recovering from knee surgery as mediators of the association between the quality of support from the spouse following surgery and recovery outcomes. RESEARCH METHOD: In-person interviews of married older adults (N = 134) with osteoarthritis of the knee who underwent total knee replacement surgery were conducted at 1 month before surgery, 1 month after surgery, and at 3 months after surgery. MAIN OUTCOME MEASURES: Outcomes were knee limitations and depressive symptoms. RESULTS: Self-efficacy mediated the associations between emotional support and problematic support and improvement in knee limitations as well as between emotional support and improvement in depressive symptoms. Perceptions of the spouse's emotional responsiveness did not mediate associations between support and recovery outcomes. CONCLUSIONS: Findings suggest that emotional support from the spouse can improve recovery outcomes in part by strengthening efficacy beliefs to manage recovery, and problematic support can hinder optimal recovery in part by weakening efficacy beliefs.