Lisa S. Parker

Managing Incidental Findings in Human Subjects Research: Analysis and Recommendations

No consensus yet exists on how to handle incidental findings (IFs) in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are findings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed.

Managing Incidental Findings and Research Results in Genomic Research Involving Biobanks and Archived Data Sets

Biobanks and archived data sets collecting samples and data have become crucial engines of genetic and genomic research. Unresolved, however, is what responsibilities biobanks should shoulder to manage incidental findings and individual research results of potential health, reproductive, or personal importance to individual contributors (using “biobank” here to refer both to collections of samples and collections of data). This article reports recommendations from a 2-year project funded by the National Institutes of Health. We analyze the responsibilities involved in managing the return of incidental findings and individual research results in a biobank research system (primary research or collection sites, the biobank itself, and secondary research sites). We suggest that biobanks shoulder significant responsibility for seeing that the biobank research system addresses the return question explicitly. When reidentification of individual contributors is possible, the biobank should work to enable the biobank research system to discharge four core responsibilities to (1) clarify the criteria for evaluating findings and the roster of returnable findings, (2) analyze a particular finding in relation to this, (3) reidentify the individual contributor, and (4) recontact the contributor to offer the finding. We suggest that findings that are analytically valid, reveal an established and substantial risk of a serious health condition, and are clinically actionable should generally be offered to consenting contributors. This article specifies 10 concrete recommendations, addressing new biobanks as well as those already in existence.Genet Med 2012:14(4):361–384

The Future of Incidental Findings: Should They Be Viewed as Benefits?:

This paper argues against considering incidental findings (IFs) as potential benefits of research when assessing the social value of proposed research, determining the appropriateness of a studys risk/benefit ratio, and identifying and disclosing the risks and benefits of participation during informed consent. The possibility of generating IFs should be disclosed during informed consent as neither a risk nor benefit, but as a possible outcome collateral to participation. Whether specific IFs will be disclosed when identified is a separate question whose answer is material to determining whether IFs constitute a risk or a potential indirect benefit of participation. Finally, three types of IF should be distinguished and treated differently during informed consent: those that will be routinely generated (e.g., results of testing to determine study eligibility), those that can reasonably be characterized in terms of their nature and frequency of generation (e.g., misattributed parentage), and those of unpredictable nature and frequency that can be characterized only in general terms. Research protocols should provide a rationale for sharing or not sharing IFs of these three types with participants. Regulatory review of such plans should not, however, be confused with regarding IFs as potential benefits when assessing the studys risk/benefit ratio or merit.

The Precision Medicine Initiative's All of Us Research Program: an agenda for research on its ethical, legal, and social issues

The Precision Medicine Initiative (PMI) is an innovative approach to developing a new model of health care that takes into account individual differences in people’s genes, environments, and lifestyles. A cornerstone of the initiative is the PMI All of Us Research Program (formerly known as PMI-Cohort Program) which will create a cohort of 1 million volunteers who will contribute their health data and biospecimens to a centralized national database to support precision medicine research. The PMI All of US Research Program is the largest longitudinal study in the history of the United States. The designers of the Program anticipated and addressed some of the ethical, legal, and social issues (ELSI) associated with the initiative. To date, however, there is no plan to call for research regarding ELSI associated with the Program-PMI All of Us program. Based on analysis of National Institutes of Health (NIH) funding announcements for the PMI All of Us program, we have identified three ELSI themes: cohort diversity and health disparities, participant engagement, and privacy and security. We review All of Us Research Program plans to address these issues and then identify additional ELSI within each domain that warrant ongoing investigation as the All of Us Research Program develops. We conclude that PMIs All of Us Research Program represents a significant opportunity and obligation to identify, analyze, and respond to ELSI, and we call on the PMI to initiate a research program capable of taking on these challenges.Genet Med advance online publication 01 December 2016

Ethical concerns in the research and treatment of complex disease

Research on and treatment of complex diseases raise familiar ethical issues concerning informed consent, privacy, confidentially, insurability, employability and social stigma. Consideration of the family as the unit of study, or point of medical intervention, presents some additional twists to these common ethical concerns. In addition, complex diseases present particular ethical challenges because different social and political incentives accompany placing emphasis on either the genetic or the environmental components of the diseases (e.g. in allocating research funds or ascribing responsibility for illness).

Prenatal whole‐exome sequencing: parental attitudes

The aim of this study was to survey the opinions of expectant parents regarding prenatal whole‐exome sequencing.

Changing interpretations, stable genes: responsibilities of patients, professionals, and policy makers in the clinical interpretation of complex genetic information

Except in rare mutation-inducing events, the primary sequence of an individuals somatic genome is static; however, the interpretations or risk predictions based on complex genetic tests now being introduced into the marketplace are rapidly changing. The reality of changing interpretations for stable test results creates questions for everyone involved in genetic testing including individuals, clinicians, laboratories, professional organizations, and regulators. Individuals should be aware that their relationship with laboratories providing genetic testing may be different from their relationship with their physician, especially in direct-to-consumer testing. Moreover, individuals may need to take the initiative to revisit their genetic test results periodically. Clinicians will need to learn how to read and interpret the results of complex genetic tests, remember that interpretations change over time, and understand when to refer patients to specialists and ask for second opinions and reinterpretation of genetic information. Testing laboratories should understand that they may be replacing the clinician as the direct contact for patients, and may have responsibility to inform clients of changes in test interpretation. At minimum, laboratories should make clear what their policies are regarding reinterpretation and allow tested individuals to seek outside interpretations of their genetic test results. Professional organizations and regulators have the responsibility to develop guidelines for clinicians, laboratories, and the general public. In the future, the interpretation of genetic tests may be relatively stable; until that time, the changing interpretation of static genetic test results will create an important set of professional and ethical challenges.

Advancing Pharmacogenomics Education in the Core PharmD Curriculum through Student Personal Genomic Testing

Objective. To develop, implement, and evaluate “Test2Learn” a program to enhance pharmacogenomics education through the use of personal genomic testing (PGT) and real genetic data. Design. One hundred twenty-two second-year doctor of pharmacy (PharmD) students in a required course were offered PGT as part of a larger program approach to teach pharmacogenomics within a robust ethical framework. The program added novel learning objectives, lecture materials, analysis tools, and exercises using individual-level and population-level genetic data. Outcomes were assessed with objective measures and pre/post survey instruments. Assessment. One hundred students (82%) underwent PGT. Knowledge significantly improved on multiple assessments. Genotyped students reported a greater increase in confidence in understanding test results by the end of the course. Similarly, undergoing PGT improved student’s self-perceived ability to empathize with patients compared to those not genotyped. Most students (71%) reported feeling PGT was an important part of the course, and 60% reported they had a better understanding of pharmacogenomics specifically because of the opportunity. Conclusion. Implementation of PGT in the core pharmacy curriculum was feasible, well-received, and enhanced student learning of pharmacogenomics.

Early intervention in pregnant women with elevated anxiety and depressive symptoms: efficacy of a cognitive-behavioral group program.

To examine whether a cognitive-behavioral group program among pregnant women with elevated levels of anxiety or depression may reduce anxious and depressive symptoms and has a positive impact on risk factors for anxiety disorders and depression. A total of 753 participants were recruited. After completion of the clinical standardized interview, 160 participants were randomized to an intervention group or a control condition. Psychometric assessments took place at T1 (preintervention), T2 (antenatal follow-up), and T3 (3 months postpartum). Analyses included women who took part in all 3 assessments (intervention group, N = 21; control group, N = 53). The subjective program evaluation by the participants was highly positive, but with the exception of a short-term effect on the quality of an intimate partnership (F1/67 = 4.056; P < .05], intervention effects on anxiety or depressive symptoms were not found. However, there was an intervention effect 3 months postpartum for participants with high depressive symptoms at T1 (Edinburgh Postnatal Depression Scale score of ≥10) (F1/69 = 5.410; P < .05). The results argue against a general efficacy of a cognitive-behavioral group program for pregnant women with rather low levels of anxiety and depression. For women with higher depressive symptoms during pregnancy, a cognitive-behavioral group program may have a positive impact on the course of depressive symptoms during the postpartum period.

Mutating concepts, evolving disciplines: Genetics, medicine, and society

Acknowledgements. 1. Introduction L.S. Parker, R.A. Ankeny. Part One: Historical Reflections on Core Concepts. 2. The Classical Gene: Its Nature and Its Legacy G.E. Allen. 3. Dissolving Dominance D. Allchin. 4. Flies, Genes, and Brains: Oskar Vogt, Nicolai Timofeeff-Resovsky, and the Origin of the Concepts of Penetrance and Expressivity M.D. Laubichler, S. Sarkar. 5. From Reproductive Responsibility to Reproductive Autonomy D. Paul. Part Two: Perspectives from the Philosophy of Science. 6. Understanding Genetic Causation and Its Implications for Ethical Issues Concerning Medical Genetics F. Gifford. 7. Reduction Reconceptualized: Cystic Fibrosis as a Paradigm Case for Molecular Medicine R.A. Ankeny. 8. Scylla and Charibdis: Adaptationism, Reductionism, and the Fallacy of Equating Race with Disease J.L. Graves Jr. 9. Behavior as Affliction: Common Frameworks of Behavior Genetics and Its Rivals H.E. Longino. Part Three: Explorations of Ethical, Social, and Legal Consequences. 10. The Morality of Prenatal Testing and Selective Abortion: Clarifying the Expressivist Objection L. Carlson. 11. Meliorism at the Millennium: Positive Molecular Eugenics and the Promise of Progress without Excess A. Silvers. 12. Personal Identity and the Moral Appraisal of Prenatal Therapy D. Wasserman. 13. Conceptual and Moral Problems of Genetic and Non-Genetic Preventive Interventions 14. Unraveling the Codes: The Dialectic between Knowledge of the Moral Person and Knowledge of the Genetic Person in Criminal Law J.H. Robinson, R.M.Berry. Notes on Contributors. Index.