Genetic Counselors’ Views and Experiences with the Clinical Integration of Genome Sequencing

In recent years, new sequencing technologies known as next generation sequencing (NGS) have provided scientists the ability to rapidly sequence all known coding as well as non-coding sequences in the human genome. As the two emerging approaches, whole exome (WES) and whole genome (WGS) sequencing, have started to be integrated in the clinical arena, we sought to survey health care professionals who are likely to be involved in the implementation process now and/or in the future (e.g., genetic counselors, geneticists and nurse practitioners). Two hundred twenty-one genetic counselors— one third of whom currently offer WES/WGS—participated in an anonymous online survey. The aims of the survey were first, to identify barriers to the implementation of WES/WGS, as perceived by survey participants; second, to provide the first systematic report of current practices regarding the integration of WES/WGS in clinic and/or research across the US and Canada and to illuminate the roles and challenges of genetic counselors participating in this process; and third to evaluate the impact of WES/WGS on patient care. Our results showed that genetic counseling practices with respect to WES/WGS are consistent with the criteria set forth in the ACMG 2012 policy statement, which highlights indications for testing, reporting, and pre/post test considerations. Our respondents described challenges related to offering WES/WGS, which included billing issues, the duration and content of the consent process, result interpretation and disclosure of incidental findings and variants of unknown significance. In addition, respondents indicated that specialty area (i.e., prenatal and cancer), lack of clinical utility of WES/WGS and concerns about interpretation of test results were factors that prevented them from offering this technology to patients. Finally, study participants identified the aspects of their professional training which have been most beneficial in aiding with the integration of WES/WGS into the clinical setting (molecular/clinical genetics, counseling and bioethics) and suggested that counseling aids (to assist them when explaining aspects of these tests to patients) and webinars focused on WES/WGS (for genetic counselors and other health care professionals) would be useful educational tools. Future research should permit us to further enhance our knowledge of pitfalls and benefits associated with the introduction of these powerful technologies in patient care and to further explore the roles and opportunities for genetic counselors in this rapidly evolving field.     

Traditional Roles in a Non-Traditional Setting: Genetic Counseling in Precision Oncology

Next generation sequencing technology is increasingly utilized in oncology with the goal of targeting therapeutics to improve response and reduce side effects. Interpretation of tumor mutations requires sequencing of paired germline DNA, raising questions about incidental germline findings. We describe our experiences as part of a research team implementing a protocol for whole genome sequencing (WGS) of tumors and paired germline DNA known as the Michigan Oncology Sequencing project (MI-ONCOSEQ) that includes options for receiving incidental germline findings. Genetic counselors (GCs) discuss options for return of results with patients during the informed consent process and document family histories. GCs also review germline findings and actively participate in the multi-disciplinary Precision Medicine Tumor Board (PMTB), providing clinical context for interpretation of germline results and making recommendations about disclosure of germline findings. GCs have encountered ethical and counseling challenges with participants, described here. Although GCs have not been traditionally involved in molecular testing of tumors, our experiences with MI-ONCOSEQ demonstrate that GCs have important applicable skills to contribute to multi-disciplinary care teams implementing precision oncology. Broader use of WGS in oncology treatment decision making and American College of Medical Genetics and Genomics (ACMG) recommendations for active interrogation of germline tissue in tumor-normal dyads suggests that GCs will have future opportunities in this area outside of research settings.     

Impact of Genomic Counseling on Informed Decision-Making among ostensibly Healthy Individuals Seeking Personal Genome Sequencing: the HealthSeq Project

Personal genome sequencing is increasingly utilized by healthy individuals for predispositional screening and other applications. However, little is known about the impact of ‘genomic counseling’ on informed decision-making in this context. Our primary aim was to compare measures of participants’ informed decision-making before and after genomic counseling in the HealthSeq project, a longitudinal cohort study of individuals receiving personal results from whole genome sequencing (WGS). Our secondary aims were to assess the impact of the counseling on WGS knowledge and concerns, and to explore participants’ satisfaction with the counseling. Questionnaires were administered to participants (n = 35) before and after their pre-test genomic counseling appointment. Informed decision-making was measured using the Decisional Conflict Scale (DCS) and the Satisfaction with Decision Scale (SDS). DCS scores decreased after genomic counseling (mean: 11.34 before vs. 5.94 after; z = ?4.34, p < 0.001, r = 0.52), and SDS scores increased (mean: 27.91 vs. 29.06 respectively; z = 2.91, p = 0.004, r = 0.35). Satisfaction with counseling was high (mean (SD) = 26.91 (2.68), on a scale where 6 = low and 30 = high satisfaction). HealthSeq participants felt that their decision regarding receiving personal results from WGS was more informed after genomic counseling. Further research comparing the impact of different genomic counseling models is needed.     

“Not Tied Up Neatly with a Bow”: Professionals’ Challenging Cases in Informed Consent for Genomic Sequencing

As the use of genomic technology has expanded in research and clinical settings, issues surrounding informed consent for genome and exome sequencing have surfaced. Despite the importance of informed consent, little is known about the specific challenges that professionals encounter when consenting patients or research participants for genomic sequencing. We interviewed 29 genetic counselors and research coordinators with considerable experience obtaining informed consent for genomic sequencing to understand their experiences and perspectives. As part of this interview, 24 interviewees discussed an informed consent case they found particularly memorable or challenging. We analyzed these case examples to determine the primary issue or challenge represented by each case. Challenges fell into two domains: participant understanding, and facilitating decisions about testing or research participation. Challenges related to participant understanding included varying levels of general and genomic literacy, difficulty managing participant expectations, and contextual factors that impeded participant understanding. Challenges related to facilitating decision-making included complicated family dynamics such as disagreement or coercion, situations in which it was unclear whether sequencing research would be a good use of participant time or resources, and situations in which the professional experienced disagreement or discomfort with participant decisions. The issues highlighted in these case examples are instructive in preparing genetics professionals to obtain informed consent for genomic sequencing.     

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.     

Genomic Counseling in the Newborn Period: Experiences and Views of Genetic Counselors

As newborn screening (NBS) technology expands, genetic counselors will become more involved in counseling for NBS results, including those potentially generated from whole exome sequencing (WES) and eventually whole genome sequencing (WGS). Members of the National Society of Genetic Counselors (NSGC) responded to an online survey (n?=?208) regarding genomic counseling in the context of NBS. The majority of participants (82.1 %) did not feel prepared to counsel for WGS results from NBS. Counselors with previous WES/WGS counseling experience felt more prepared (p?=?0.005) to counsel for WGS results from NBS than those without WES/WGS experience. Overall, counselors expressed ethical and practical concerns regarding WGS in NBS, as well as a need for additional training regarding this application of the technology before it is implemented. Based on the results of this study, genetic counselors voice caution to the larger genetics community regarding expansion of NBS to incorporate genomic sequencing and advocate for additional education prior to initiating WGS into NBS.     

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.     

Clinical and Counseling Experiences of Early Adopters of Whole Exome Sequencing

Currently, there are limited data regarding the practice of genetic counseling for whole exome sequencing (WES). Improved understanding of how genetic counselors and other providers are educating, counseling, and communicating results may identify practice trends, and patient or provider needs. Between April 2013 and December 2014, we surveyed providers who ordered WES testing from GeneDx, a CLIA-certified laboratory. Forty-nine respondents completed the survey; 41 % of participants reported board certification in genetic counseling. Pre-test and post-test counseling was completed in all but one case each. Pre-test counseling lasted less than 1 h for 53 % of cases and 1 to 2 h for 43 %. Topics discussed with all patients included consent for testing, and incidental findings; other topics were variable. In contrast to pre-test counseling, 59 % reported post-test counseling lasting 1 to 2 h and 33 % less than an hour; post-testing counseling was significantly longer in cases with a definitive diagnosis than those without (p?=?0.0129). The survey findings indicate some variability regarding the amount of time spent on counseling and the topics discussed during pre-test counseling. Additional exploration, patient and provider educational resources, and potentially more specific guidelines regarding counseling for WES may be warranted.     

Assessing the Ethics of Medical Research in Emergency Settings: How Do International Regulations Work in Practice?

Different ethical principles conflict in research conducted in emergency research. Clinical care and its development should be based on research. Patients in critical clinical condition are in the greatest need of better medicines. The critical condition of the patient and the absence of a patient representative at the critical time period make it difficult and sometimes impossible to request an informed consent before the beginning of the trial. In an emergency, care decisions must be made in a short period of time, and the more time is wasted, the more the risk of death or severe tissue damage and incapacity increases. Consent requests take time, and so the time period before treatment might put the patient’s life in jeopardy. Not requesting consent before a trial is also contradictory. A person should not be forced to participate in a trial against his or her will. Due to the dark history of medical research previously, international declarations and conventions have set up ethical principles for medical research. They emphasize the autonomy of the research participant—or his or her legal representative—to give a free and informed consent prior to the initiation of research. In the case of a critical emergency, the unconscious state of the patient, the emotional stress of family members or the lack of time to start life-sustaining measures may often restrict the possibilities of communicating with the patient or his/her representative. Therefore, written informed consent is difficult to achieve, and its voluntariness in emergency situations is, at best, open to question. The mortality of patients is high without clinical interventions in emergency research. Random selection of patients is difficult and requires extra work from personnel in the emergency rooms. Recruitment, information and asking for consent may also take time, postpone the initiation of treatment and increase the risk of death and irreversible tissue and organ damage, and therefore be risky for the patient. It is therefore essential that the health care professionals recruiting suitable research participants are well motivated and well trained. Medical research in an emergency setting should always be regarded as an exceptional situation requiring special provisions. Only such research should be done as cannot be done in other conditions. An independent body must approve the research protocol and the ways in which the consent of the participant or proxy are to be sought. In addition, the trial must be expected to result in direct and significant benefit for the research participants. If research without prior consent is not approved, the development of emergency care is threatened. On the other hand, if prior consent is not required, a person could be recruited into a clinical trial against his or her will. Doing good and avoiding harm, and respecting the autonomy of the patient are in conflict in the context of emergency medical research. To develop better medicines for patients experiencing acute medical emergencies, research into such conditions should be allowed. Research participants should have the possibility to participate or refuse to participate in research that may benefit them and other patients. The risk of irreversible damage occurring as the consequence of time delays for seeking consent is unacceptable. A prior wish about participation in clinical trials should be respected, if known. The conditions under which medical research in emergencies can be considered acceptable can be determined and agreed upon nationally and internationally. An earlier version of this paper was presented at The 7th International Conference on Bioethics on “The Ethics of Research in Emergency Medicine”, held on June 2, 2006, Warsaw, Poland.     

Participant protection with the use of records: ethical issues and recommendations

This article explores the ethical concerns and protections that may be required when individually identifiable data originally collected solely for clinical or administrative purposes are used in research or evaluation. It asks the following broad question with respect to the interim policy developed by the Substance Abuse and Mental Health Services Administration (SAMHSA) to protect the rights and welfare of participants in its programs: For those programs and projects not classified as research, are the protections and system for review adequate? Background information on SAMHSA's interim policy is provided, along with issues and questions related to the use of clinical and administrative records in research and evaluation. The article concludes with recommendations for modifying the existing participant protection guidelines, based on the preceding discussion of issues and questions.     

Characteristics of adult day care participants who enter a nursing home

The authors sought to determine the characteristics of individuals enrolled in adult day care who are most likely to enter a nursing home. The status of 201 adult day care participants was assessed at baseline and at least 3 years after baseline evaluation. Risk factors for nursing home entry were identified on the basis of staff and family caregiver reports, participant testing, chart review, and physician evaluations. Cox regression analyses of baseline data such as medical diagnoses, affect, and demographic information were used to identify risk factors for institutionalization. Multivariate Cox regression analysis identified depressed affect of the care recipient as an important predictor of institutionalization; other predictors were low frequency of socializing with relatives and friends, higher number of psychiatric diagnoses, and increased age. The findings highlight the importance of socialization and suggest that a focus on successful and reinforcing socialization should be an important component of adult day care programming. The results also suggest that addressing patient mental health variables may be important in delaying institutionalization in this population.     

Research Participants’ Preferences for Hypothetical Secondary Results from Genomic Research

Secondary or incidental results can be identified in genomic research that increasingly uses whole exome/genome sequencing. Understanding research participants’ preferences for secondary results and what influences these decisions is important for patient education, counseling, and consent, and for the development of policies regarding return of secondary results. Two hundred nineteen research participants enrolled in genomic studies were surveyed regarding hypothetical preferences for specific types of secondary results, and these preferences were correlated with demographic information and psychosocial data. The majority of research participants (73%) indicated a preference to learn about all results offered, with no clear pattern regarding which results were not desired by the remaining participants. Participants who reported greater interest in genetic privacy were less likely to indicate a preference to learn all results, as were individuals who self-identified as Jewish. Although most research participants preferred to receive all secondary results offered, a significant subset preferred to exclude some results, suggesting that an all-or-none policy would not be ideal for all participants. The correlations between preferences to receive secondary results, religious identification, and privacy concerns demonstrate the need for culturally sensitive counseling and educational materials accessible to all education levels to allow participants to make the best choices for themselves.     

时间定价对亲社会行为的影响

时间定价就是将金钱价格赋予时间之上,用金钱来衡量时间的价值。已有研究表明,时间定价激活时间经济价值最大化的心理定势,使个体更看重时间的经济回报,花更少的时间帮助他人。但是,时间定价对亲社会行为的影响可能并不仅仅局限于时间利他。本研究通过三个实验,除了考察时间定价对时间利他的影响外,还进一步探讨时间定价对金钱利他的影响。结果显示,时间定价不仅影响个体的时间利他行为,也削弱了金钱利他行为。这表明,时间定价所激活的经济效用心理定势不仅仅局限于时间这一种资源的效用。     

When clinical care is like research: the need for review and consent

The prevailing “segregated model” for understanding clinical research sharply separates it from clinical care and subjects it to extensive regulations and guidelines. This approach is based on the fact that clinical research relies on procedures and methods—research biopsies, blinding, randomization, fixed treatment protocols, placebos—that pose risks and burdens to participants in order to collect data that might benefit all patients. Reliance on these methods raises the potential for exploitation and unfairness, and thus points to the need for independent ethical review and more extensive informed consent. In contrast, it is widely assumed that clinical care does not raise these ethical concerns because it is designed to promote the best interests of individual patients. The segregation of clinical research from clinical care has been largely effective at protecting research participants. At the same time, this approach ignores the fact that several aspects of standard clinical care, such as clinician training and scheduling, also pose some risks and burdens to present patients for the benefit of all patients. We argue that recently proposed learning health care systems offer a way to address this concern, and better protect patients, by developing integrated review and consent procedures. Specifically, current approaches base the need for independent ethical review and more extensive informed consent on whether an activity is categorized as clinical research or clinical care. An ethically sounder approach, which could be incorporated into learning health care systems, would be to base the need for independent ethical review and more extensive informed consent on the extent to which an activity poses risks to present patients for the benefit of all patients.     

A comparison of token and tandem schedules of reinforcement on response patterns for adolescents with autism

Token schedules of reinforcement are ubiquitous in clinical settings, yet little research has thoroughly evaluated the effects of token schedules on responding in clinical settings. Basic research has shown token schedules of reinforcement produce lower response rates and larger pre‐ratio pauses compared to tandem schedules. The purpose of the current study was to determine whether the same effects are produced with adolescents with autism or related disorders. We examined response patterns under otherwise identical FR token and FR tandem schedules. Tokens suppressed responding for one participant only under high schedule values and for a second participant under common clinical schedule values; no difference in responding occurred between token and tandem schedules for two participants. These results support the systematic evaluation of token schedules of reinforcement in clinical settings. Additional applied research is needed on token schedules to further our understanding of the underlying mechanisms that contribute to the overall effectiveness of token economies.     

Understanding Adult Participant and Parent Empowerment Prior to Evaluation in the Undiagnosed Diseases Network

The burden of living with an undiagnosed condition is high and includes physical and emotional suffering, frustrations, and uncertainty. For patients and families experiencing these stressors, higher levels of empowerment may be associated with better outcomes. Thus, it is important to understand the experiences of patients with undiagnosed conditions and their families affected by undiagnosed conditions in order to identify strategies for fostering empowerment. In this study, we used the Genetic Counseling Outcome Scale (GCOS-24) to assess levels of empowerment and support group participation in 35 adult participants and 67 parents of child participants in the Undiagnosed Diseases Network (UDN) prior to their UDN in-person evaluation. Our results revealed significantly lower empowerment scores on the GCOS-24 in adult participants compared to parents of child participants [t(100)?=???3.01, p?=?0.003, average difference?=???11.12, 95% CI (??3.78, ??18.46)] and no significant association between support group participation and empowerment scores. The majority of participants (84.3%, 86/102) are not currently participating in any support groups, and participation rates were not significantly different for adult participants and parents of child participants (11.4 vs. 19.7%, respectively, FE p?=?0.40). Open-ended responses provided additional insight into support group participation, the challenges of living with undiagnosed conditions, and positive coping strategies. Future research will evaluate the extent to which empowerment scores change as participation in the UDN unfolds.     

Group interventions for patients with cancer and HIV disease: Part I: Effects on psychosocial and functional outcomes at different phases of illness

Group interventions for individuals facing cancer or HIV disease have drawn considerable attention among researchers and clinicians over the past 20 years. There is growing evidence that group services may be helpful, but which interventions are most effective for participants at which phases in the trajectory of disease has been less clear. Moreover, professionals working in different intervention settings (e.g., primary prevention vs. clinical care) and different disease sites (cancer vs. HIV disease) often have little awareness of relevant advances in other fields. Efforts to integrate findings in the literature may accelerate research and advance the standard of clinical care. The current article, the first in a series of four special reports, critically evaluates the efficacy of group interventions led by professional or trained facilitators for individuals confronted by cancer or HIV, across the spectrum of illness from elevated risk through advanced disease. We examine psychosocial and functional outcomes for different interventions directed toward different patient subgroups, trace common themes, highlight limitations, and offer recommendations for further research.