Julianne M. O'Daniel

Survey of US public attitudes toward pharmacogenetic testing.

To assess public attitudes and interest in pharmacogenetic (PGx) testing, we conducted a random-digit-dial telephone survey of US adults, achieving a response rate of 42% (n=1139). Most respondents expressed interest in PGx testing to predict mild or serious side effects (73±3.29 and 85±2.91%, respectively), guide dosing (91%) and assist with drug selection (92%). Younger individuals (aged 18–34 years) were more likely to be interested in PGx testing to predict serious side effects (vs aged 55+ years), as well as Whites, those with a college degree, and who had experienced side effects from medications. However, most respondents (78±3.14%) were not likely to have a PGx test if there was a risk that their DNA sample or test result could be shared without their permission. Given differences in interest among some groups, providers should clearly discuss the purpose of testing, alternative testing options (if available) and policies to protect patient privacy and confidentiality.

Public Perspectives on Returning Genetics and Genomics Research Results

Background: The debate about returning research results has revealed different perspectives among researchers, participants and advisory groups with participants generally interested in obtaining their results. Given this preference, policies regarding return of individual research results may affect whether a potential subject chooses to participate in a study. Public attitudes, particularly those of African-Americans, toward this issue have been understudied. Methods: In 2008–2009, we convened 10 focus groups in Durham, N.C. to explore attitudes about returning research results and how different policies might influence their likelihood to participate in genetic/genomic studies. Transcripts were complimented by a short anonymous survey. Of 100 participants, 73% were female and 76% African-American with a median age of 40–49 years. Results: Although there was general interest in obtaining genetics research results, particularly individual results, discussants recognized many potential complexities. The option to obtain research results (individual or summary) was clearly valued and lack thereof was potentially a deterrent for genetic/genomic research enrollment. Conclusions: Providing the option to learn research results may help strengthen relationships between investigators and participants and thereby serve as a positive influencing factor for minority communities. Consideration of the broader implications of returning research results is warranted. Engaging diverse publics is essential to gain a balance between the interests and burdens of participants and investigators.

Public Perspectives About Pharmacogenetic Testing and Managing Ancillary Findings

AIMS Pharmacogenetic (PGx) tests are intended to improve therapeutic outcomes through predicting a patients likelihood to respond to or experience an adverse effect from a specific treatment. In addition, PGx testing may also generate ancillary, or incidental, disease information unrelated to the purpose for which the test was ordered. To assess public attitudes toward PGx testing, ancillary disease risk information and related clinical issues, we conducted a series of focus groups. RESULTS Forty-five individuals recruited from Durham, NC, participated in four focus groups. Overall, participants were enthusiastic about PGx testing, though expressed concerns about privacy, confidentiality, and psychological harms associated with ancillary information. Focus group participants believed that physicians had a responsibility to disclose ancillary risk information, but were concerned about managing and coping with unexpected disease risk information. CONCLUSION We find that participants welcomed the integration of PGx testing into therapeutic decision-making. Public concerns about PGx testing and ancillary information specifically centered on personal implications of learning such additional information, suggesting that patient-provider discussion of the benefits and risks of testing will be necessary until public familiarity with these tests increases.

Whole-genome and whole-exome sequencing in hereditary cancer: impact on genetic testing and counseling.

AbstractThe incorporation of whole-genome and whole-exome sequencing into clinical practice will undoubtedly change the way genetic counselors and other clinicians approach genetic testing. Enabling the analysis of essentially all human genes in one comprehensive test, this new technology can result in reduced testing cost and time to diagnosis. Another consequence of this broad scope, however, is the increased amount, complexity, and variety of results a clinician may need to discuss with a patient. The purpose of this article is to review the technology and outline some of the benefits and challenges of whole-genome and whole-exome sequencing in hereditary cancer practice.

Public perspectives regarding data-sharing practices in genomics research

Background: Genomics research data are often widely shared through a variety of mechanisms including publication, meetings and online databases. Re-identification of research participants from sequence data has been shown possible, raising concerns of participants’ privacy. Methods: In 2008–09, we convened 10 focus groups in Durham, N.C. to explore attitudes about how genomic research data were shared amongst the research community, communication of these practices to participants and how different policies might influence participants’ likelihood to consent to a genetic/genomic study. Focus groups were audio-recorded and transcripts were complemented by a short anonymous survey. Of 100 participants, 73% were female and 76% African-American, with a median age of 40–49 years. Results: Overall, we found that discussants expressed concerns about privacy and confidentially of data shared through online databases. Although discussants recognized the benefits of data-sharing, they believed it was important to inform research participants of a study’s data-sharing plans during the informed consent process. Discussants were significantly more likely to participate in a study that planned to deposit data in a restricted access online database compared to an open access database (p < 0.00001). Conclusions: The combination of the potential loss of privacy with concerns about data access and identity of the research sponsor warrants disclosure about a study’s data-sharing plans during the informed consent process.

A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing.

Purpose:As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis.Methods:We established a semiquantitative metric to assess five elements of actionability: severity and likelihood of the disease outcome, efficacy and burden of intervention, and knowledge base, with a total score from 0 to 15.Results:The semiquantitative metric was applied to a list of putative actionable conditions, the list of genes recommended by the American College of Medical Genetics and Genomics (ACMG) for return when deleterious variants are discovered as secondary/incidental findings, and a random sample of 1,000 genes. Scores from the list of putative actionable conditions (median = 12) and the ACMG list (median = 11) were both statistically different than the randomly selected genes (median = 7) (P < 0.0001, two-tailed Mann-Whitney test).Conclusion:Gene–disease pairs having a score of 11 or higher represent the top quintile of actionability. The semiquantitative metric effectively assesses clinical actionability, promotes transparency, and may facilitate assessments of clinical actionability by various groups and in diverse contexts.Genet Med 18 5, 467–475.

Factors Influencing Uptake of Pharmacogenetic Testing in a Diverse Patient Population

Background: The successful integration of pharmacogenetic (PGx) testing into clinical care will require attention to patient attitudes. In this study, we aimed to identify the major reasons why patients would or would not consider PGx testing and whether these factors differed by race, socioeconomic and insurance status, and medical history. Methods: We developed and conducted a survey within the adult patient population of the Duke Family Medicine Center. Results: Of 75 completed surveys (65% African-American), 77% indicated they were ‘very likely’ or ‘somewhat likely’ to take a PGx test. Respondents who had experienced a side effect were significantly more likely to indicate they would take a PGx test and expressed greater interest in learning more about testing than those who had not. Drug safety and effectiveness were the major reasons to have PGx testing. Privacy concerns and lack of insurance coverage for testing were the major reasons to decline testing. Conclusions: We found no differences in interest in PGx tests by race or socioeconomic status, but found stronger interest from those with a history of side effects and private insurance. While the overall support of PGx testing is encouraging, greater reassurance of medical privacy and development of educational resources are needed.

Enhancing geneticists’ perspectives of the public through community engagement

Purpose:Given the rapid pace of genetic and genomic research and technology development, public engagement on scientific issues may be mutually beneficial to the research community and the general public. The public may benefit from a greater understanding of concepts and new applications, and researchers can build awareness of public knowledge, perceptions, and potential concerns about genomic research and applications.Methods:We developed and piloted a public engagement program called Genome Diner to facilitate dialog between genetic/genomic researchers (n = 40) and middle school students (n = 76) and their parents (n = 83) from the local community. Program impact was assessed through pre- and post-Diner surveys for each group.Results:After participation in Genome Diner, researchers’ views were positively affected regarding the (adult) public’s level of understanding of genetic concepts, beliefs about relevance of research, and the importance of researcher–community interaction.Conclusion:Through an interactive discussion with students and parents, researchers gained valuable insight into public perspectives about genome research. The engagement format of the Genome Diner program presents a novel method of fostering trust and relationships between the two groups and to inform both the public and the researchers, whose work may depend on public opinion and participation.Genet Med 2012:14(2):243–249

The Potential of a Placebo/Nocebo Effect in Pharmacogenetics

Pharmacogenetic testing holds great promise to improve health outcomes and reduce adverse drug responses through enhanced selection of therapeutic agents. Since drug responses can be manipulated by verbal suggestions, it is of particular interest to understand the potential impact of pharmacogenetic test results on drug response. Placebo and nocebo-like effects may be possible due to the suggestive nature of pharmacogenetic information that a drug will or will not likely lead to improved health outcomes. For example, pharmacogenetic testing could provide further reassurance to patients that a given drug will be effective and/or cause minimal side effects. However, pharmacogenetic information could adversely affect drug response through negative expectations that a drug will be less than optimally effective or cause an adverse response, known as a nocebo-like effect. Therefore, a patient’s perceived value of testing, their understanding of the test results, and the manner in which they are communicated may influence therapeutic outcome. As such, physicians should consider the potential effect of pharmacogenetic test results on therapeutic outcome when communicating results to patients. Studies are needed to investigate the impact of pharmacogenetic information of therapeutic outcome.

CORRIGENDUM: ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing

Genet Med (2013) 15, 565–574 doi:10.1038/gim.2013.73 In the published version of this paper, on page 567, on the 16th line in the last paragraph of the left column, the abbreviation of Expected Pathogenic is incorrect. The correct sentence should read, “For the purposes of these recommendations, variants fitting these descriptions were labeled as Known Pathogenic (KP) and Expected Pathogenic (EP), respectively.