Diana Harris

Stakeholders’ Opinions on the Implementation of Pediatric Whole Exome Sequencing: Implications for Informed Consent

Advances in whole genome and whole exome sequencing (WGS/WES) technologies have led to increased availability in clinical settings. Currently, there are few guidelines relating to the process and content of informed consent for WGS/WES, nor to which results should be returned to families. To address this gap, we conducted focus groups to assess the views of professionals, parents, and adolescents for the future implementation of WES. The discussions assessed understanding of the risks and benefits of WES, preferences for the informed consent discussion, process for return of results, and the decision-making role of the pediatric patient. Professional focus group participants included bioethicists, physicians, laboratory directors, and genetic counselors. Parent focus groups included individuals with children who could be offered sequencing due to a potential genetic cause of the child’s condition. On-line discussion groups were conducted with adolescents aged 13–17 who had a possible genetic disorder. We identified discrepancies between professionals and patient groups regarding the process and content of informed consent, preference for return of results, and the role of the child in decision-making. Professional groups were concerned with the uncertainty regarding professional obligations, changing interpretation in genomic medicine, and practical concerns of returning results over time. Parent and adolescent groups focused on patient choice and personal utility of sequencing results. Each group expressed different views on the role of the child in decision-making and return of results. These discrepancies represent potential barriers to informed consent and a challenge for genetic counselors regarding the involvement of pediatric patients in decision-making and return of results discussions.

Measuring Children's Decision-Making Involvement Regarding Chronic Illness Management

OBJECTIVES To develop a measure of decision-making involvement in children and adolescents with cystic fibrosis, diabetes, and asthma. METHODS Parent-child dyads completed the Decision-Making Involvement Scale (DMIS) and measures of locus of control and family communication. DMIS items were subjected to exploratory and confirmatory factor analysis (CFA). Temporal stability and construct validity were assessed. RESULTS The parent form was reduced to 20 items representing five factors. CFA showed that the five factors were an acceptable fit to the parent- and child-report data. Internal consistency values ranged from 0.71 to 0.91. Temporal stability was supported by moderate-substantial intraclass correlation coefficients. DMIS subscales were associated with child age, child locus of control, and family communication. CONCLUSIONS The DMIS can be used to inform our understanding of the transition to greater independence for illness management. Additional research is needed to examine outcomes of decision-making involvement, including treatment adherence and responsibility.

The Decision Making Control Instrument to Assess Voluntary Consent

Background. The decision to participate in a research intervention or to undergo medical treatment should be both informed and voluntary. Objective. The aim of the present study was to develop an instrument to measure the perceived voluntariness of parents making decisions for their seriously ill children. Methods. A total of 219 parents completed questionnaires within 10 days of making such a decision at a large, urban tertiary care hospital for children. Parents were presented with an experimental form of the Decision Making Control Instrument (DMCI), a measure of the perception of voluntariness. Data obtained from the 28-item form were analyzed using a combination of both exploratory and confirmatory factor analytic techniques. Results. The 28 items were reduced to 9 items representing 3 oblique dimensions: Self-Control, Absence of Control, and Others’ Control. The hypothesis that the 3-factor covariance structure of our model was consistent with that of the data was supported. Internal consistency for the scale as a whole was high (0.83); internal consistency for the subscales ranged from 0.68 to 0.87. DMCI scores were associated with measures of affect, trust, and decision self-efficacy, supporting the construct validity of the new instrument. Conclusion. The DMCI is an important new tool that can be used to inform our understanding of the voluntariness of treatment and research decisions in medical settings.

Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing

Purpose:The risks, benefits, and utilities of multiplex panels for breast cancer susceptibility are unknown, and new counseling and informed consent models are needed. We sought to obtain patient feedback and early outcome data with a novel tiered-binned model for multiplex testing.Methods:BRCA1/2-negative and untested patients completed pre- and posttest counseling and surveys evaluating testing experiences and cognitive and affective responses to multiplex testing.Results:Of 73 patients, 49 (67%) completed pretest counseling. BRCA1/2-negative patients were more likely to proceed with multiplex testing (86%) than those untested for BRCA1/2 (43%; P < 0.01). Many patients declining testing reported concern for uncertainty and distress. Most patients would not change anything about their pre- (76%) or posttest (89%) counseling sessions. Thirty-three patients (72%) were classified as making an informed choice, including 81% of those who proceeded with multiplex testing. Knowledge increased significantly. Anxiety, depression, uncertainty, and cancer worry did not significantly increase with multiplex testing.Conclusion:Some patients, particularly those without prior BRCA1/2 testing, decline multiplex testing. Most patients who proceeded with testing did not experience negative psychological responses, but larger studies are needed. The tiered-binned approach is an innovative genetic counseling and informed consent model for further study in the era of multiplex testing.Genet Med 18 1, 25–33.

Family care giving for patients at life's end: report from the cultural variations study (CVAS).

OBJECTIVE To investigate differences between African American and White family caregivers in self-reported health, use of social support and external resources, and emotional and financial strain in the context of their care of a family member with advanced cancer. METHODS Sixty-nine patient-designated family caregivers of patients with advanced lung or colon cancer interviewed between December 1999 and July 2001. RESULTS Most African American and White family caregivers were able to identify someone else who was helping them in the care of their family member. Few caregivers used outside resources (e.g., home-based medical care, meal delivery, pastoral care, outside social support visitor) to assist in the support and care of the patient. At baseline, White caregivers were more likely to agree that caregiving caused work adjustments, (p=.28, p=.02) and emotional difficulties (p=.32, p=.008) and that caregiving had been completely overwhelming (p=.19, p=.12) than were African American caregivers. At follow-up, among family caregivers of patients who had died, 44% reported having to quit work to provide personal care for the patient. Twenty-five percent of family caregivers reported using most or all of the familys saving in caring for the patient. SIGNIFICANCE OF RESULTS Caregivers of patients at end of life experience substantial emotional and financial difficulties related to caregiving. Family caregiving is a private undertaking with little use of outside resources to mitigate the burden.

Utilizing Remote Real-Time Videoconferencing to Expand Access to Cancer Genetic Services in Community Practices: A Multicenter Feasibility Study

Background Videoconferencing has been used to expand medical services to low-access populations and could increase access to genetic services at community sites where in-person visits with genetic providers are not available. Objective To evaluate the feasibility of, patient feedback of, and cognitive and affective responses to remote two-way videoconferencing (RVC) telegenetic services at multiple sociodemographically diverse community practices without access to genetic providers. Methods Patients at 3 community sites in 2 US states outside the host center completed RVC pretest (visit 1, V1) and post-test (visit 2, V2) genetic counseling for cancer susceptibility. Surveys evaluated patient experiences, knowledge, satisfaction with telegenetic and cancer genetics services, anxiety, depression, and cancer worry. Results A total of 82 out of 100 (82.0%) approached patients consented to RVC services. A total of 61 out of 82 patients (74%) completed pretest counseling and 41 out of 61 (67%) proceeded with testing and post-test counseling. A total of 4 out of 41 (10%) mutation carriers were identified: BRCA2, MSH2, and PMS2. Patients reported many advantages (eg, lower travel burden and convenience) and few disadvantages to RVC telegenetic services. Most patients reported feeling comfortable with the video camera—post-V1: 52/57 (91%); post-V2: 39/41 (95%)—and that their privacy was respected—post-V1: 56/57 (98%); post-V2: 40/41 (98%); however, some reported concerns that RVC might increase the risk of a confidentiality breach of their health information—post-V1: 14/57 (25%); post-V2: 12/41 (29%). While the majority of patients reported having no trouble seeing or hearing the genetic counselor—post-V1: 47/57 (82%); post-V2: 39/41 (95%)—51 out of 98 (52%) patients reported technical difficulties. Nonetheless, all patients reported being satisfied with genetic services. Compared to baseline, knowledge increased significantly after pretest counseling (+1.11 mean score, P=.005); satisfaction with telegenetic (+1.74 mean score, P=.02) and genetic services (+2.22 mean score, P=.001) increased after post-test counseling. General anxiety and depression decreased after pretest (-0.97 mean anxiety score, P=.003; -0.37 mean depression score, P=.046) and post-test counseling (-1.13 mean anxiety score, P=.003; -0.75 mean depression score, P=.01); state anxiety and cancer-specific worry did not significantly increase. Conclusions Remote videoconferencing telegenetic services are feasible, identify genetic carriers in community practices, and are associated with high patient satisfaction and favorable cognitive and affective outcomes, suggesting an innovative delivery model for further study to improve access to genetic providers and services. Potential barriers to dissemination include technology costs, unclear billing and reimbursement, and state requirements for provider licensure.

Human Subjects Protection: An Event Monitoring Committee for Research Studies of Girls from Breast Cancer Families

PURPOSE Researchers must monitor the safety of research participants, particularly in studies involving children and adolescents. Yet, there is limited guidance for the development and implementation of oversight committees for psychosocial, behavioral intervention, and observational studies. METHODS We implemented a model for an Event Monitoring Committee (EMC) in three related studies recruiting 6- to 19-year-old girls from families with and without breast cancer. RESULTS The EMC model can be valuable for investigators and local institutional review boards when additional oversight is desired. Recommendations are provided and intended to be broadly applicable to a wide range of research activities designed to improve the health of children, adolescents, and families. EMC goals, membership, and procedures for monitoring and assessing risks and benefits should be defined but should also be flexible and tailored to the study design and population. The EMC model also provides an independent comprehensive, study-wide oversight mechanism for multicenter psychosocial, behavioral intervention, and observational studies. CONCLUSIONS An EMC provides an alternative oversight approach where additional independent assessment and oversight of study-related risks are desired, particularly in the setting of vulnerable populations, children and adolescents, or where risks nontraditional to the medical field (i.e., social, emotional, or cultural) are possible.

Abstract P1-11-02: Telemedicine: Expanding access to cancer genetic services to underserved populations

Background: Given the increasing demand for genetic services and limited genetic workforce, many patients do not receive recommended pre- and post-test genetic counseling. Telemedicine has been used to expand specialized medical services to low access populations. The feasibility and outcomes of telemedicine in clinical genetics are not well described. Methods: Patients at 3 community sites without genetic counseling services received real-time pre-test (V1) and post-test (V2) counseling for cancer susceptibility with a genetic counselor (GC) at a center of expertise via community sites’ and host institution’s computers equipped with web cameras and videoconferencing software. Mixed-methods surveys assessed patient knowledge, satisfaction, psychosocial responses and experiences at baseline (BL), post-V1 and post-V2. We used paired T-tests to assess change between time points and linear regressions. Results: Of 100 patients approached, 83% consented to telegenetic services. To date, 57 have completed BL and V1, and 70% proceeded with genetic testing, 31 patients have received results, including 3 carriers (BRCA2, MSH2, PMS2). Patient characteristics did not differ between those who agreed to and declined telegenetics. 4% of sessions were aborted due to technology failures. 30% experienced disconnections but were completed. Nearly all (94%) were satisfied with their telegenetic experience. Knowledge and satisfaction with telegenetic services significantly increased and general anxiety and depression significantly decreased. Event related (state) anxiety did not change significantly. Patients reported several advantages to telegenetics (e.g. decreased travel burden) and few disadvantages (e.g. audio challenges and technical glitches).Conclusions: Telemedicine delivery of cancer genetic services is feasible, identifies genetic mutation carriers, increases knowledge, decreases anxiety and depression and is associated with high satisfaction, suggesting an innovative model for delivery of genetic services for patients and community practices without access to local genetic providers. Citation Format: Linda Patrick-Miller, Diana Harris, Evelyn Stevens, Brian Egleston, Linda Fleisher, Rebbeca Mueller, Amanda Brandt, Jill Stopfer, Susan Domchek, Angela Bradbury. Telemedicine: Expanding access to cancer genetic services to underserved populations [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-11-02.