Genetic Counseling Practice in Next Generation Sequencing Research: Implications for the Ethical Oversight of the Informed Consent Process

The potential for next generation sequencing research (NGS) to generate individual genetic results could have implications for the informed consent process and the provision of genetic counseling. We undertook a content analysis of informed consent templates and guidelines produced by Canadian institutional review boards, purposively sampling documents used by researchers to obtain consent from participants in genetics studies. Our goal was to examine the extent to which the informed consent documents addressed genetic counseling and the return of individual genetic results. Our analysis reveals that the majority of informed consent documents did not mention genetic counseling while several did not mention the return of results. We found differences in the ways in which documents addressed availability of counseling, eligibility criteria for referral to a genetic counselor, genetic counselor involvement, provision of services to family members of participants and incidental findings. From an ethical standpoint, consent documents should provide appropriate information so that participants may make an informed decision about their participation in research. The need to ensure adequate counseling for study populations in an NGS research context will necessarily involve adapting values that underlie care in genetic counseling practice. If the interests of research participants are to be truly promoted, the drafting and review of informed consent documents should give proper due to genetic counseling.     

Interest and Beliefs About BRCA Genetic Counseling Among At-Risk Latinas in New York City

Background: Latinas are less likely to use genetic services (counseling and testing) for hereditary breast and/or ovarian cancer risk compared to other ethnic groups. Meanwhile, little is known about barriers to genetic counseling among Latinas at increased risk of inherited breast cancer. Methods: A two-phase pilot study was conducted to examine interest, barriers and beliefs about BRCA genetic counseling among at-risk Latinas in New York City and explore the potential for developing a culturally-tailored narrative educational tool for use in future studies. Phase 1 included quantitative telephone interviews (N = 15) with bilingual participants with a personal diagnosis at a young age and/or family history of breast and/or ovarian cancer. Quantitative results informed development of a narrative prototype educational presentation viewed by a subset of participants (N = 10) in Phase 2 focus groups. Results: Despite barriers, including lack of awareness/knowledge, concerns related to learning cancer risks of family members, and concerns about cost/health insurance, participants reported positive attitudes, beliefs and interest in learning about BRCA genetic counseling. Further, significant increases in knowledge were demonstrated from pre-post presentation (p = 0.04). Conclusion: There is an unmet need to educate at-risk Latinas about BRCA genetic counseling. Culturally-tailored educational materials including narratives may increase knowledge about BRCA genetic counseling among this underserved group. The effectiveness of these approaches should be tested in future research with larger samples.     

Collecting Informed Consent with Juvenile Justice Populations: Issues and Implications for Research

Researchers must provide participants with opportunities to make informed decisions about whether to participate in research studies. Investigators conducting research with youth in the juvenile justice system face unique ethical, legal, and practical challenges to obtaining informed consent. Juvenile justice researchers must navigate multiple legal and ethical standards for collecting informed consent, take into account youths’ dual vulnerabilities as children and prisoners, and overcome practical limitations to obtaining parental/guardian permission. Given the challenges and complexity of obtaining standard informed consent of youth in juvenile justice facilities, this paper provides suggestions for overcoming obstacles to recruiting these youth for research participation. It offers guidance for fostering the enrollment of juvenile justice youth in research studies using procedures that comply with ethical and legal standards for research with this dually vulnerable population. Copyright © 2013 John Wiley & Sons, Ltd.     

An Ethical Exploration of Barriers to Research on Controlled Drugs

We examine the ethical, social, and regulatory barriers that may hinder research on therapeutic potential of certain controversial controlled substances like marijuana, heroin, or ketamine. Hazards for individuals and society and potential adverse effects on communities may be good reasons for limiting access and justify careful monitoring of these substances. Overly strict regulations, fear of legal consequences, stigma associated with abuse and populations using illicit drugs, and lack of funding may, however, limit research on their considerable therapeutic potential. We review the surprisingly sparse literature and address the particular ethical concerns pertinent to research with illicit and addictive substances, such as undue inducement, informed consent, therapeutic misconception, and risk to participants, researchers, and institutions. We consider the perspectives of key research stakeholders and explore whether they may be infected with bias. We conclude by proposing an empirical research agenda to provide an evidentiary basis for ethical reasoning.     

Large,Prospective Analysis of the Reasons Patients Do Not Pursue <Emphasis Type="Italic">BRCA</Emphasis> Genetic Testing Following Genetic Counseling

Genetic counseling (GC) and genetic testing (GT) identifies high-risk individuals who benefit from enhanced medical management. Not all individuals undergo GT following GC and understanding the reasons why can impact clinical efficiency, reduce GT costs through appropriate identification of high-risk individuals, and demonstrate the value of pre-GT GC. A collaborative project sponsored by the Michigan Department of Health and Human Services prospectively collects anonymous data on BRCA-related GC visits performed by providers in Michigan, including demographics, patient/family cancer history, GT results, and reasons for declining GT. From 2008 to 2012, 10,726 patients underwent GC; 3476 (32.4%) did not pursue GT. Primary reasons included: not the best test candidate (28.1%), not clinically indicated (23.3%), and insurance/out of pocket cost concerns (13.6%). Patient disinterest was the primary reason for declining in 17.1%. Insurance/out of pocket cost concerns were the primary reason for not testing in 13.4% of untested individuals with private insurance. Among untested individuals with breast and/or ovarian cancer, 22.5% reported insurance/out of pocket cost concerns as the primary reason for not testing and 6.6% failed to meet Medicare criteria. In a five-year time period, nearly one-third of patients who underwent BRCA GC did not pursue GT. GT was not indicated in almost half of patients. Insurance/out of pocket cost concerns continue to be barriers.     

Reasons for Declining Preconception Expanded Carrier Screening Using Genome Sequencing

Genomic carrier screening can identify more disease-associated variants than existing carrier screening methodologies, but its utility from patients’ perspective is not yet established. A randomized controlled trial for preconception genomic carrier screening provided an opportunity to understand patients’ decisions about whether to accept or decline testing. We administered a survey to potential genomic carrier screening recipients who declined participation (N = 240) to evaluate their reasons for doing so. Two thirds of women declined participation. We identified major themes describing reasons these individuals declined to participate; the most common were time limitation, lack of interest, not wanting to know the information, and potential cause of worry or anxiety. Most women eligible for genomic carrier screening indicated that their reasons for opting out were due to logistical issues rather than opposing the rationale for testing. As expanded carrier screening and genomic sequencing become a more routine part of clinical care, it is anticipated there will be variable uptake from individuals for this testing. Thus, the advancement of clinical carrier screening from single genes, to expanded screening panels, to an exome- or genome-wide platform, will require approaches that respect individual choice to receive genetic testing for reproductive risk assessment.     

A Comparison of Enrollees Versus Non-enrollees in a Patient/Family HCV Psychoeducation Study

Despite the seriousness of Hepatitis C (HCV), many patients do not receive treatment. One promising means of addressing these issues for medically ill patients is through participation in support group services. This study examined individual-, treatment- and system-level factors associated with enrolling in a support group intervention (psychoeducation) for persons with HCV. A total of 235 research participants were recruited as part of a NIAAA-funded randomized clinical trial for patients with HCV and their family members, with 172 (73.2 %) agreeing to enroll in the psychoeducation trial and 63 (26.8 %) declining. Factors leading to enrollment indicated that individuals without employment, with certain personality structures (low cooperativeness and self-directedness), and traveling greater distance to their group were more likely to agree to participate. Populations being seen in public settings demonstrate a desire for additional support and education, but at the same time these potential participants are faced with challenges to following through and enrolling in the desired services.     

Facilitators and Barriers to Engagement in Home Visitation

Abstract

Given previous findings indicating a positive association between home visitation participation rates and family outcomes, the present study explored reasons for and barriers to engagement in the first six months of these parenting programs. Social support, psychoeducation, and tangible assistance emerged as consistent themes across informants as reasons for participation. Perceived invasiveness of the assessments, maternal concerns about being reported to child protective services, and mismatches between maternal needs and home visitor attributes emerged as recurrent themes regarding barriers to participation. Results of these qualitative analyses converge with previous quantitative research regarding factors associated with home visitation delivery and suggest new areas in need of further inquiry by researchers and practitioners to increase engagement.     

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.     

Factors Influencing Clinical Follow-Up for Individuals with a Personal History of Breast and/or Ovarian Cancer and Previous Uninformative <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> Testing

Genetic testing for inherited cancer risk has recently improved through the advent of multi-gene panels and the addition of deletion and duplication analysis of the BRCA genes. The primary aim of this study was to determine which factors influence the intent of individuals with a personal history of breast and/or ovarian cancer and negative or uncertain BRCA1 and BRCA2 testing to return to a hereditary cancer program for additional genetic risk assessment, counseling, and testing. Surveys were sent to 1197 individuals and 257 were returned. Of those participants who were planning to return to clinic, most cited having family members who could benefit from the test result as the primary motivation to return. Many participants who were not planning to return to clinic cited the cost of testing as a barrier to return. Cost of testing and concerns about insurance coverage were the most commonly cited barriers for the group of participants who were undecided about returning to clinic. Results from this study may be used to guide re-contact efforts by clinicians to increase patient uptake to return to clinic for up-to-date genetic risk assessment, counseling, and testing.     

Re-evaluating the therapeutic misconception: response to Miller and Joffe

Responding to the paper by Miller and Joffe, we review the development of the concept of therapeutic misconception (TM). Our concerns about TM's impact on informed consent do not derive from the belief that research subjects have poorer outcomes than persons receiving ordinary clinical care. Rather, we believe that subjects with TM cannot give an adequate informed consent to research participation, which harms their dignitary interests and their abilities to make meaningful decisions. Ironically, Miller and Joffe's approach ends up largely embracing the very position that they inaccurately attribute to us: the belief that, with some exceptions, it is only the prospect of poorer outcomes that should motivate efforts to dispel TM. In the absence of empirical studies on the steps required to dispel TM and the impact of such procedures on subject recruitment, it is premature to surrender to the belief that TM must be widely tolerated in clinical research.     

Development and Pilot Testing of a Decision Aid for Genomic Research Participants Notified of Clinically Actionable Research Findings for Cancer Risk

Germline genomic testing is increasingly used in research to identify genetic causes of disease, including cancer. However, there is evidence that individuals who are notified of clinically actionable research findings have difficulty making informed decisions regarding uptake of genetic counseling for these findings. This study aimed to produce and pilot test a decision aid to assist participants in genomic research studies who are notified of clinically actionable research findings to make informed choices regarding uptake of genetic counseling. Development was guided by published literature, the International Patient Decision Aid Standards, and the expertise of a steering committee of clinicians, researchers, and consumers. Decision aid acceptability was assessed by self-report questionnaire. All 19 participants stated that the decision aid was easy to read, clearly presented, increased their understanding of the implications of taking up research findings, and would be helpful in decision-making. While low to moderate levels of distress/worry were reported after reading the booklet, a majority of participants also reported feeling reassured. All participants would recommend the booklet to others considering uptake of clinically actionable research findings. Results indicate the decision aid is acceptable to the target audience, with potential as a useful decision support tool for genomic research participants.     

The Risks,Benefits, and Ethics of Trauma-Focused Research Participation

With the rising interest in the field of trauma research, many Institutional Review Boards, policymakers, parents, and others grapple with the impact of trauma-research participation on research participants' well-being. Do individuals who participate in trauma-focused research risk experiencing lasting negative effects from participation? What are the potential benefits that may be gleaned from participation in this work? How can trauma research studies be designed ethically, minimizing the risk to participants? The following review seeks to answer these questions. This review indicates that most studies in this area have found that only a minority of participants experience distress when participating in trauma-focused research. Furthermore, these negative feelings tend to dissipate quickly over time, with the majority of participants self-appraising their participation as positive, rewarding, and beneficial to society. Design characteristics that may serve to minimize participants' risk of experiencing distress are discussed, as well as implications for public policy and future research.     

Time Costs for Genetic Counseling in Preconception Carrier Screening with Genome Sequencing

Advances in technology and the promise of personalized health care are driving greater use of genome sequencing (GS) for a variety of clinical scenarios. As health systems consider adopting GS, they need to understand the impact of GS on the organization and cost of care. While research has documented a dramatic decrease in the cost of sequencing and interpreting GS, few studies have examined how GS impacts genetic counseling workloads. This study examined the time needed to provide genetic counseling for GS in the context of preconception carrier screening. Genetic counselors prospectively reported on the time spent in the results disclosure process with 107 study participants who were part of the NextGen study. We found that the median time for results disclosure was 64 min (ranged from 5 to 229 min). Preparation work was the most time-consuming activity. Qualitative data from journal entries, debrief interviews with genetic counselors, and detailed case conference notes provided information on factors influencing time for results disclosure and implications for practice. Results suggest that expanded carrier screening could require significant increases in genetic counseling time, unless we are able to generate new resources to reduce preparation work or develop other strategies such as the creation of new models to deliver this type of service.     

“My Plate is Full”: Reasons for Declining a Genetic Evaluation of Hearing Loss

The aim of this study was to obtain patient and parent perspectives on genetic evaluation of hearing loss, in order to identify motivators, expectations, and barriers. Three focus groups were conducted following a semi-structured discussion guide, led by an independent moderator. Participants were hearing parents of children with permanent hearing loss or deaf adults. Qualitative content analysis was used to develop a codebook and identify major themes and subthemes. Participant views were compared to national guidelines. The 28 participants comprised 23 parents representing 21 unique families and 5 deaf adults. 13/21 families and 0/5 adults reported comorbidities, 4/21 families and 3/5 adults had a positive family history, and 12/21 families versus 0/5 adults had utilized genetics services. A common theme among adults and parents was a curiosity as to the cause of hearing loss. Parents were motivated to detect comorbidities and optimize care for hearing loss. Some parents felt overwhelmed by the hearing loss and unprepared to pursue early genetic evaluation as recommended in guidelines. Several reported positive experiences following genetics consultation, while others reported unease and unmet expectations. Notably, both parents and adults expressed ambivalence regarding the desire for genetic knowledge. Financial concerns and difficulties obtaining a referral were cited as extrinsic barriers. For parents of children with hearing loss, both the presence of comorbidities and a positive family history were drivers of genetics consultation and/or genetic testing. We identified educational opportunities for both patients and providers that would improve informed decision-making and increase access to genetic services. Consideration of the patient/family perspective and their decision-making processes, along with flexibility in the approach to genetics evaluation and its timing, will optimize both the development and implementation of guidelines.     

Conducting Health Disparities Research with Criminal Justice Populations: Examining Research,Ethics, and Participation

This study explored the challenges of informed consent and understanding of the research process among Black and Latino men under community supervision (e.g., parole and/or probation). Between February and October 2012, we conducted cognitive face-to-face interviews using open-ended questions on the significant areas of research participation (i.e., the informed consent process, confidentiality, compensation, what is meant by human subject and clinical trials) among 259 men aged 35 to 67 under community supervision in Bronx, New York. Content analysis of the open-ended questions revealed limited knowledge concerning the understanding of research participation. The study participants appeared to generally understand concepts such as compensation after research participation and confidentiality. Participants demonstrated a lack of understanding of certain aspects of the research process—informed consent, human subject, Institutional Review Board, and clinical trials. These findings are informative to researchers conducting studies with criminal justice populations and Institutional Review Boards reviewing research studies.