Testing a deliberative democracy method with citizens of African ancestry to weigh pros and cons of targeted screening for hereditary breast and ovarian cancer risk.

Background: Democratic deliberation (DD), a strategy to foster co-learning among researchers and communities, could be applied to gain informed public input on health policies relating to genomic translation. Purpose: We evaluated the quality of DD for gaining informed community perspectives regarding targeting communities of African Ancestry (AAn) for Hereditary Breast and Ovarian Cancer (HBOC) screening in Georgia. Methods: We audiotaped a 2.5 day conference conducted via zoom in March 2021 to examine indicators of deliberation quality based on three principles: (1) inclusivity (diverse viewpoints based on participants' demographics, cancer history, and civic engagement), (2) consideration of factual information (balanced and unbiased expert testimonies, participant perceived helpfulness), and (3) deliberation (speaking opportunities, adoption of a societal perspective on the issue, reasoned justification of ideas, and participant satisfaction). Results: We recruited 24 participants who reflected the diversity of views and life experiences of citizens of AAn living in Georgia. The expert testimony development process we undertook for creating balanced factual information was endorsed by experts' feedback. Deliberation process evaluation showed that while participation varied (average number of statements = 24, range: 3-62), all participants contributed. Participants were able to apply expert information and take a societal perspective to deliberate on the pros and cons of targeting individuals of AAn for HBOC screening in Georgia. Conclusions: The rigorous process of public engagement using deliberative democracy approach can successfully engage a citizenry with diverse and well-informed views, do so in a relatively short time frame and yield perspectives based on high quality discussion.

Adolescent and parent perspectives on genomic sequencing to inform cancer care.

Next-generation sequencing offers opportunities for targeted cancer therapies and may identify pathogenic germline variants. Adolescents' perception of testing is not well understood. We surveyed 16 adolescents and 59 parents regarding motivations, attitudes, and knowledge related to paired tumor/germline sequencing. Participants generally had a good objective understanding of germline genetics and cancer risk, with parents scoring higher than adolescents. Nearly all participants were motivated by a desire to help other patients and to treat their child/themselves. Most adolescents reported involvement in the decision to enroll in the study. Study findings suggest important similarities and differences between parent and adolescent views.

Huntington's Disease Community Perspectives on Desired Characteristics of Disease Modifying Therapies.

Background: Promising disease modifying therapies for Huntington's disease are now entering pivotal trials, raising questions of what patients and families consider successful outcomes. Consistent with an ongoing movement to incorporate patient preferences into the development of new therapies, we conducted a pilot study to assess Huntington's disease community views on emerging DMTs to assist in planning large-scale studies of patient preferences. Methods: Semi-structured interviews were conducted with members of the Huntington's community (manifest disease, at-risk, and family/caregivers). Participants were asked which symptoms they believed should be targeted with novel treatments, as well as potential benefits and tradeoffs of delaying symptom onset versus prolonging late-stage disease. Results: Participants (N = 14) emphasized the need for treatments improving cognitive and/or behavioral symptoms. Many wanted treatments that delayed symptom onset up to 5-10 years, though some considered shorter delays acceptable due to potential value in advancing research to help future generations. Concern regarding potential for prolonging later-stage disease was variable, with some participants uncertain if they would want a treatment that delayed onset but prolonged later-stage disease. Others stated that any delay in onset would be desirable, regardless of potential prolongation of later stage disease. Discussion: This study demonstrates a breadth of opinions among the Huntington's disease community surrounding both the benefits and complex tradeoffs that might occur with disease modifying treatments. These preliminary findings will inform future large-scale studies of attitudes toward disease modifying treatments, which may ultimately guide the design and outcome measure selection for clinical trials. Highlights: In-depth interviews with the Huntington's disease community were used to explore patient and family preferences regarding potential disease modifying therapies. Many wanted symptom delay of 5-10 years, though some considered shorter delays acceptable for altruistic reasons. Opinions on trade-offs varied, suggesting larger preference studies are needed to inform trial design.

Patient Preferences Regarding Informed Consent Models for Participation in a Learning Health Care System for Oncology.

PURPOSE: The expansion of learning health care systems (LHSs) promises to bolster research and quality improvement endeavors. Stewards of patient data have a duty to respect the preferences of the patients from whom, and for whom, these data are being collected and consolidated. METHODS: We conducted democratic deliberations with a diverse sample of 217 patients treated at 4 sites to assess views about LHSs, using the example of CancerLinQ, a real-world LHS, to stimulate discussion. In small group discussions, participants deliberated about different policies for how to provide information and to seek consent regarding the inclusion of patient data. These discussions were recorded, transcribed, and de-identified for thematic analysis. RESULTS: Of participants, 67% were female, 61% were non-Hispanic Whites, and the mean age was 60 years. Patients' opinions about sharing their data illuminated 2 spectra: trust/distrust and individualism/collectivism. Positions on these spectra influenced the weight placed on 3 priorities: promoting societal altruism, ensuring respect for persons, and protecting themselves. In turn, consideration of these priorities seemed to inform preferences regarding patient choices and system transparency. Most advocated for a policy whereby patients would receive notification and have the opportunity to opt out of including their medical records in the LHS. Participants reasoned that such a policy would balance personal protections and societal welfare. CONCLUSION: System transparency and patient choice are vital if patients are to feel respected and to trust LHS endeavors. Those responsible for LHS implementation should ensure that all patients receive an explanation of their options, together with standardized, understandable, comprehensive materials.

Patient and Provider Perspectives Regarding Enrollment in Head and Neck Cancer Research.

OBJECTIVE: The advent of precision oncology complicates how clinicians and participants understand how clinical care and research interface. Here we examine how key stakeholders perceive the utility of, and evaluate the decision to participate in, genomic sequencing head and neck cancer research. The goal of this study was to highlight unique considerations for our community as this type of research proliferates across the country. STUDY DESIGN: Prospective multimethod qualitative and quantitative embedded ethics protocol. SETTING: Single-institution National Cancer Institute-designated academic cancer center. SUBJECTS AND METHODS: Multimethod study using paired surveys and semistructured interviews among patients and providers involved in a prospective precision head and neck oncology sequencing protocol (116 survey patient-participants, response rate 82%) with 18 interviewees. RESULTS: Participants were generally enthusiastic about enrollment in research, both to help future patients and as a way of giving back to the community. They described reliance on information from and trust in their cancer doctor regarding the decision to participate in research, but paradoxically there was discordance in how doctors and patients reported their respective influence in the decision-making process. Clinicians also stressed the importance in separating clinical and research-informed consent processes, although patients did not describe this tension. CONCLUSION: As we enter an era of increasing personalized medicine and targeted therapies, the relationship between clinicians, scientists, and patients plays a larger role in how we individualize and contextualize cancer research. Our data are another step toward the ultimate goal of respecting and protecting patients as participants in head and neck translational oncology.

What Clinical Ethics Can Learn From Decision Science.

Many components of decision science are relevant to clinical ethics practice. Decision science encourages thoughtful definition of options, clarification of information needs, and acknowledgement of the heterogeneity of people's experiences and underlying values. Attention to decision-making processes reminds participants in consultations that how decisions are made and how information is provided can change a choice. Decision science also helps reveal affective forecasting errors (errors in predictions about how one will feel in a future situation) that happen when people consider possible future health states and suggests strategies for correcting these and other kinds of biases. Implementation of decision science innovations is not always feasible or appropriate in ethics consultations, but their uses increase the likelihood that an ethics consultation process will generate choices congruent with patients' and families' values.

Effect of Public Deliberation on Patient Attitudes Regarding Consent and Data Use in a Learning Health Care System for Oncology.

PURPOSE: We sought to generate informed and considered opinions regarding acceptable secondary uses of deidentified health information and consent models for oncology learning health care systems. METHODS: Day-long democratic deliberation sessions included 217 patients with cancer at four geographically and sociodemographically diverse sites. Patients completed three surveys (at baseline, immediately after deliberation, and 1-month follow-up). RESULTS: Participants were 67.3% female, 21.7% black, and 6.0% Hispanic. The most notable changes in perceptions after deliberation related to use of deidentified medical-record data by insurance companies. After discussion, 72.3% of participants felt comfortable if the purpose was to make sure patients receive recommended care (v 79.5% at baseline; P = .03); 24.9% felt comfortable if the purpose was to determine eligibility for coverage or reimbursement (v 50.9% at baseline; P < .001). The most notable change about secondary research use related to believing it was important that doctors ask patients at least once whether researchers can use deidentified medical-records data for future research. The proportion endorsing high importance decreased from baseline (82.2%) to 68.7% immediately after discussion (P < .001), and remained decreased at 73.1% (P = .01) at follow-up. At follow-up, non-Hispanic whites were more likely to consider it highly important to be able to conduct medical research with deidentified electronic health records (96.8% v 87.7%; P = .01) and less likely to consider it highly important for doctors to get a patient's permission each time deidentified medical record information is used for research (23.2% v 51.6%; P < .001). CONCLUSION: This research confirms that most patients wish to be asked before deidentified medical records are used for research. Policies designed to realize the potential benefits of learning health care systems can, and should be, grounded in informed and considered public opinion.

Interpretations of the Term "Actionable" when Discussing Genetic Test Results: What you Mean Is Not What I Heard.

In genomic medicine, the familiarity and inexactness of the term "actionable" can lead to multiple interpretations and mistaken beliefs about realistic treatment options. As part of a larger study focusing on public attitudes toward policies for the return of secondary genomic results, we looked at how members of the lay public interpret the term "medically actionable" in the context of genetic testing. We also surveyed a convenience sample of oncologists as part of a separate study and asked them to define the term "medically actionable." After being provided with a definition of the term, 21 out of 60 (35%) layperson respondents wrote an additional action not specified in the provided definition (12 mentioned "cure" and 9 mentioned environment or behavioral change) and 17 (28%) indicated "something can be done" with no action specified. In contrast, 52 surveyed oncologists did not mention environment, behavioral change, or cure. Based on our findings, we propose that rather than using the term "actionable" alone, providers should also say "what they mean" to reduce miscommunication and confusion that could negatively impact medical decision-making. Lastly, to guide clinicians during patient- provider discussion about genetic test results, we provide examples of phrasing to facilitate clearer communication and understanding of the term "actionable."

Next-generation sequencing in precision oncology: Patient understanding and expectations.

BACKGROUND: Implementation of precision oncology interventions poses several challenges to informed consent and patient education. This study assessed cancer patients' understanding, expectations, and outcomes regarding participation in research examining the impact of matched tumor and germline sequencing on their clinical care. METHODS: A total of 297 patients (mean age: 59 years; 50% female; 96% white) with refractory, metastatic cancer were surveyed, including 217 who completed surveys both before and after undergoing integrated whole exome and transcriptome sequencing as part of a larger clinical research study. RESULTS: At baseline, the vast majority of patients expected to receive several potential direct benefits from study participation, including written reports of sequencing findings (88%), greater understanding of the causes of their cancer (74%), and participation in clinical trials for which sequencing results would make them eligible (84%). In most cases, these benefits were not realized by study completion. Despite explanations from study personnel to the contrary, most participants (67%-76%) presumed that incidental germline sequencing findings relevant to noncancerous health conditions (eg, diabetes) would automatically be disclosed to them. Patients reported low levels of concern about study risks at baseline and low levels of regret about study participation at follow-up. CONCLUSIONS: Findings suggest that cancer patients participating in precision oncology intervention research have largely unfulfilled expectations of direct benefits related to their study participation. Increased focus on patient education to supplement the informed consent process may help manage patients' expectations regarding the extent and likelihood of benefits received as a result of undergoing genomic sequencing.

Knowledge regarding and patterns of genetic testing in patients newly diagnosed with breast cancer participating in the iCanDecide trial.

BACKGROUND: The current study reports rates of knowledge regarding the probability of a BRCA1 and/or S pathogenic variant and genetic testing in patients with breast cancer, collected as part of a randomized controlled trial of a tailored, comprehensive, and interactive decision tool (iCanDecide). METHODS: A total of 537 patients newly diagnosed with early-stage breast cancer were enrolled at the time of their first visit in 22 surgical practices, and were surveyed 5 weeks (496 patients; Response Rate [RR], 92%) after enrollment after treatment decision making. Primary outcomes included knowledge regarding the probability of carrying a BRCA1 and/or BRCA2 pathogenic variant and genetic testing after diagnosis. RESULTS: Overall knowledge regarding the probability of having a BRCA1 and/or BRCA2 pathogenic variant was low (29.8%). Significantly more patients in the intervention group compared with the control group had knowledge regarding the probability of a BRCA1 and/or BRCA2 pathogenic variant (35.8% vs 24.4%; P <.006). In multivariable logistic regression, the intervention arm remained significantly associated with knowledge regarding the probability of having a BRCA1 and/or BRCA2 pathogenic variant (odds ratio, 1.79; 95% confidence interval, 1.18-2.70). CONCLUSIONS: The results of the current study suggest that although knowledge concerning the probability of having a BRCA1 and/or BRCA2 pathogenic variant remains low in this patient population, the interactive decision tool improved rates compared with a static Web site. As interest in genetic testing continues to rise, so will the need to integrate tools into the treatment decision process to improve informed decision making.

Encouraging Participation And Transparency In Biobank Research.

Medical biobanks often struggle to obtain sustainable funding. Commercialization of specimens is one solution, but disclosure of commercial interests to potential contributors can be dissuasive. Recent revisions to the federal human subjects research regulations will soon mandate such commercialization disclosure in some circumstances, which raises questions about implications for practice. In this nationally representative, probability-based survey sample of the US adult population, we found that 67 percent of participants agreed that clear notification of potential commercialization of biospecimens is warranted, but only 23 percent were comfortable with such use. Sixty-two percent believed that profits should be used only to support future research, and 41 percent supported sharing profits with the public. We also considered other factors related to disclosure in our analysis and argue for a "disclosure plus" standard: informing potential contributors that their biospecimens might be accessed by commercial organizations and explaining how profits would be used to both enhance transparency and facilitate contributors' altruistic motivations.

Oncologists' Use of Genomic Sequencing Data to Inform Clinical Management.

PURPOSE: To determine whether oncologists intended to change treatment as a result of tumor sequencing, and subsequently, whether patients experienced an alteration of clinical management or derived clinical benefit. PATIENTS AND METHODS: A prospective survey of oncologists referring adult patients with rare, advanced, or refractory cancer to the Michigan Oncology Sequencing program was conducted from June 2014 to March 2015 to assess the use of and intent to disclose sequencing findings. Oncologists' responses were compared with the referred patients' self-reported survey responses, and a content analysis of disclosure documented in the medical record was performed. Medical records were reviewed retrospectively to determine if clinical management was informed or changed by sequencing results. RESULTS: Oncologists (response rate, 93%) referring 112 consecutive patients were surveyed. Medical records of patients were reviewed for changes in clinical management on the basis of sequencing findings. Oncologists intended to change the treatment of 22% of patients (n = 24) on the basis of sequencing findings. Of these patients, 37.5% (n = 9) had an actual change in clinical management. Thirty-four patients with postsequencing survey data reported that a results disclosure discussion did not occur, despite documentation of disclosure by the physician in the medical record. CONCLUSIONS: Findings demonstrate that many oncologists view next-generation sequencing results to be potentially valuable in directing subsequent therapy for their patients; however, barriers in communicating results to patients and implementing them in clinical management remain.

Family History Collection Practices: National Survey of Pediatric Primary Care Providers.

While family history (FH) collection is a core responsibility of pediatric primary care providers (PCPs), few details about this practice are known. We surveyed a random national sample of 1200 pediatricians and family medicine physicians about FH collection practices. A total of 86% of respondents (n = 289 pediatricians; n = 152 family medicine physicians) indicated that they collect a FH "always" or "most of the time" with 77% reporting collection at the first visit, regardless of whether it is a health maintenance or problem-focused visit. Less than half ask about relatives other than parents, siblings, or grandparents (36.3%). Among respondents, 42% routinely update the FH at every health maintenance visit while 6% updated FH at every visit. Pediatric PCPs use a variety of methods to collect a FH that is limited in scope and variably updated. Our results suggest that interventions are needed to help pediatric PCPs collect a systematic, efficient, and updated FH.

Public's Views toward Return of Secondary Results in Genomic Sequencing: It's (Almost) All about the Choice.

The therapeutic use of genomic sequencing creates novel and unresolved questions about cost, clinical efficacy, access, and the disclosure of sequencing results. The disclosure of the secondary results of sequencing poses a particularly challenging ethical problem. Experts disagree about which results should be shared and public input - especially important for the creation of disclosure policies - is complicated by the complex nature of genetics. Recognizing the value of deliberative democratic methods for soliciting informed public opinion on matters like these, we recruited participants from a clinical research site for an all-day deliberative democracy (DD) session. Participants were introduced to the clinical and ethical issues associated with genomic sequencing, after which they discussed the tradeoffs and offered their opinions about policies for the return of secondary results. Participants (n = 66; mean age = 57 (SD = 15); 70% female; 76% white) were divided into 10 small groups (5 to 8 participants each) allowing interactive deliberation on policy options for the return of three categories of secondary results: 1) medically actionable results; 2) risks for adult-onset disorders identified in children; and 3) carrier status for autosomal recessive disorders. In our qualitative analysis of the session transcripts, we found that while participants favored choice and had a preference for making information available, they also acknowledged the risks (and benefits) of learning such information. Our research reveals the nuanced reasoning used by members of the public when weighing the pros and cons of receiving genomic information, enriching our understanding of the findings of surveys of attitudes regarding access to secondary results.

Direct-to-Consumer Genetic Testing: User Motivations, Decision Making, and Perceived Utility of Results.

BACKGROUND/AIMS: To describe the interests, decision making, and responses of consumers of direct-to-consumer personal genomic testing (DTC-PGT) services. METHODS: Prior to 2013 regulatory restrictions on DTC-PGT services, 1,648 consumers from 2 leading companies completed Web surveys before and after receiving test results. RESULTS: Prior to testing, DTC-PGT consumers were as interested in ancestry (74% very interested) and trait information (72%) as they were in disease risks (72%). Among disease risks, heart disease (68% very interested), breast cancer (67%), and Alzheimer disease (66%) were of greatest interest prior to testing. Interest in disease risks was associated with female gender and poorer self-reported health (p < 0.01). Many consumers (38%) did not consider the possibility of unwanted information before purchasing services; this group was more likely to be older, male, and less educated (p < 0.05). After receiving results, 59% of respondents said test information would influence management of their health; 2% reported regret about seeking testing and 1% reported harm from results. CONCLUSION: DTC-PGT has attracted controversy because of the health-related information it provides, but nonmedical information is of equal or greater interest to consumers. Although many consumers did not fully consider potential risks prior to testing, DTC-PGT was generally perceived as useful in informing future health decisions.

Effect of Public Deliberation on Attitudes toward Return of Secondary Results in Genomic Sequencing.

The increased use of genomic sequencing in clinical diagnostics and therapeutics makes imperative the development of guidelines and policies about how to handle secondary findings. For reasons both practical and ethical, the creation of these guidelines must take into consideration the informed opinions of the lay public. As part of a larger Clinical Sequencing Exploratory Research (CSER) consortium project, we organized a deliberative democracy (DD) session that engaged 66 participants in dialogue about the benefits and risks associated with the return of secondary findings from clinical genomic sequencing. Participants were educated about the scientific and ethical aspects of the disclosure of secondary findings by experts in medical genetics and bioethics, and then engaged in facilitated discussion of policy options for the disclosure of three types of secondary findings: 1) medically actionable results; 2) adult onset disorders found in children; and 3) carrier status. Participants' opinions were collected via surveys administered one month before, immediately following, and one month after the DD session. Post DD session, participants were significantly more willing to support policies that do not allow access to secondary findings related to adult onset conditions in children (Χ 2 (2, N = 62) = 13.300, p = 0.001) or carrier status (Χ 2 (2, N = 60) = 11.375, p = 0.003). After one month, the level of support for the policy denying access to secondary findings regarding adult-onset conditions remained significantly higher than the pre-DD level, although less than immediately post-DD (Χ 2 (1, N = 60) = 2.465, p = 0.041). Our findings suggest that education and deliberation enhance public appreciation of the scientific and ethical complexities of genome sequencing.

A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories.

PURPOSE: While the diagnostic success of genomic sequencing expands, the complexity of this testing should not be overlooked. Numerous laboratory processes are required to support the identification, interpretation, and reporting of clinically significant variants. This study aimed to examine the workflow and reporting procedures among US laboratories to highlight shared practices and identify areas in need of standardization. METHODS: Surveys and follow-up interviews were conducted with laboratories offering exome and/or genome sequencing to support a research program or for routine clinical services. The 73-item survey elicited multiple choice and free-text responses that were later clarified with phone interviews. RESULTS: Twenty-one laboratories participated. Practices highly concordant across all groups included consent documentation, multiperson case review, and enabling patient opt-out of incidental or secondary findings analysis. Noted divergence included use of phenotypic data to inform case analysis and interpretation and reporting of case-specific quality metrics and methods. Few laboratory policies detailed procedures for data reanalysis, data sharing, or patient access to data. CONCLUSION: This study provides an overview of practices and policies of experienced exome and genome sequencing laboratories. The results enable broader consideration of which practices are becoming standard approaches, where divergence remains, and areas of development in best practice guidelines that may be helpful.Genet Med advance online publication 03 Novemeber 2016.

How Well Do Customers of Direct-to-Consumer Personal Genomic Testing Services Comprehend Genetic Test Results? Findings from the Impact of Personal Genomics Study.

AIM: To assess customer comprehension of health-related personal genomic testing (PGT) results. METHODS: We presented sample reports of genetic results and examined responses to comprehension questions in 1,030 PGT customers (mean age: 46.7 years; 59.9% female; 79.0% college graduates; 14.9% non-White; 4.7% of Hispanic/Latino ethnicity). Sample reports presented a genetic risk for Alzheimer's disease and type 2 diabetes, carrier screening summary results for >30 conditions, results for phenylketonuria and cystic fibrosis, and drug response results for a statin drug. Logistic regression was used to identify correlates of participant comprehension. RESULTS: Participants exhibited high overall comprehension (mean score: 79.1% correct). The highest comprehension (range: 81.1-97.4% correct) was observed in the statin drug response and carrier screening summary results, and lower comprehension (range: 63.6-74.8% correct) on specific carrier screening results. Higher levels of numeracy, genetic knowledge, and education were significantly associated with greater comprehension. Older age (≥ 60 years) was associated with lower comprehension scores. CONCLUSIONS: Most customers accurately interpreted the health implications of PGT results; however, comprehension varied by demographic characteristics, numeracy and genetic knowledge, and types and format of the genetic information presented. Results suggest a need to tailor the presentation of PGT results by test type and customer characteristics.

Impact of non-welfare interests on willingness to donate to biobanks: an experimental survey.

The ethical debate surrounding biobanks has focused on protecting donors' welfare and privacy. However, little attention has been given to the ethical significance of donor interests that go beyond privacy and welfare (non-welfare interests [NWIs]), such as their concerns about the moral or religious implications of researchers using their donated samples. Using an experimental survey design with 1,276 participants recruited via Amazon Mechanical Turk (MTurk), we studied the potential impact of eight NWI scenarios on people's attitudes toward research studies being performed on samples donated to biobanks by assessing willingness to donate, attitudes toward disclosure of NWIs, impact of timing and format of disclosure (number of NWIs disclosed on a page), and participant factors associated with willingness to donate. Baseline willingness to donate to biobanks prior to any mention of NWIs was comparable with previous studies, at 85% to 89%. Most participants wanted NWI disclosures prior to donation to biobanks, but far fewer favored specific consent. Overall pattern of responses showed that as participants receive more information about NWIs, willingness to donate decreases in a scenario dependent manner. Specifically, NWI concerns about profit seeking research and insurance risk assessment had the strongest impact, even greater than controversial issues such as reproductive research, regardless of political, religious, and most other characteristics of respondents. Based on the results, a schema of NWI types is proposed that could be used for further research and policy discussions.