Informed consent and community engagement in open field research: lessons for gene drive science
Debate                                      
Jerome Amir Singh
BMC Medical Ethics, 27 July 2019; 20(54) 
Open Access
Abstract
Background
The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene drive constructs to reduce or suppress mosquito populations to levels that do not support disease transmission. Despite this prospect, social resistance to genetically modified organisms remains high. Gene drive open field research thus raises important questions regarding what is owed to those who may not consent to such research, or those could be affected by the proposed research, but whose consent is not solicited. The precise circumstances under which informed consent must be obtained, and from whom, requires careful consideration. Furthermore, appropriate engagement processes should be central to any introduction of genetically modified mosquitos in proposed target settings.
Discussion
In this work, international guidance documents on informed consent and engagement are reviewed and applied to the genetically modified mosquito research context. Five analogous research endeavours that involve area-wide / open field experiments are reviewed. The approach of each in respect to the solicitation of individual informed consent and community engagement are highlighted.
Conclusions
While the solicitation of individual informed consent in host settings of gene drive field trials may not be possible or feasible in some instances, local community and stakeholder engagement will be key to building trust towards the proposed conduct of such research. In this regard, the approaches taken by investigators and sponsors of political science field research and weather modification field research should be avoided. Rather, proponents of gene drive field research should look to the Eliminate Dengue field trials, cluster randomised trials, and pragmatic clinical trials for guidance regarding how the solicitation of individual informed consent of host communities ought to be managed, and how these communities ought to be engaged.

Consent and Autonomy in the Genomics Era
Rachel Horton, Anneke Lucassen
Current Genetic Medicine Reports, 2 May 2019; 7(2) pp 85–91
Abstract
Purpose of Review
Genomic tests offer increased opportunity for diagnosis, but their outputs are often uncertain and complex; results may need to be revised and/or may not be relevant until some future time. We discuss the challenges that this presents for consent and autonomy.
Recent Findings
Popular discourse around genomic testing tends to be strongly deterministic and optimistic, yet many findings from genomic tests are uncertain or unclear. Clinical conversations need to anticipate and potentially challenge unrealistic expectations of what a genomic test can deliver in order to enhance autonomy and ensure that consent to genomic testing is valid.
Summary
We conclude that ‘fully informed’ consent is often not possible in the context of genomic testing, but that an open-ended approach is appropriate. We consider that such broad consent can only work if located within systems or organisations that are trustworthy and that have measures in place to ensure that such open-ended agreements are not abused. We suggest that a relational concept of autonomy has benefits in encouraging focus on the networks and relationships that allow decision making to flourish.

Consent and Autonomy in the Genomics Era
Review
Rachel Horton, Anneke Lucassen
Current Genetic Medicine Reports, 2 May 2019; Cancer Genomics, pp 1–7
Abstract
Purpose of Review
Genomic tests offer increased opportunity for diagnosis, but their outputs are often uncertain and complex; results may need to be revised and/or may not be relevant until some future time. We discuss the challenges that this presents for consent and autonomy.
Recent Findings
Popular discourse around genomic testing tends to be strongly deterministic and optimistic, yet many findings from genomic tests are uncertain or unclear. Clinical conversations need to anticipate and potentially challenge unrealistic expectations of what a genomic test can deliver in order to enhance autonomy and ensure that consent to genomic testing is valid.
Summary
We conclude that ‘fully informed’ consent is often not possible in the context of genomic testing, but that an open-ended approach is appropriate. We consider that such broad consent can only work if located within systems or organisations that are trustworthy and that have measures in place to ensure that such open-ended agreements are not abused. We suggest that a relational concept of autonomy has benefits in encouraging focus on the networks and relationships that allow decision making to flourish.

NGS-Based genetic testing for heritable cardiovascular diseases. Specific requirements for obtaining informed consent
JörgSchmidtke, KathrinWittkowski, RalfGlaubitz
Molecular and Cellular Probes, 3 May 2019
Abstract
Clinical genetic testing in cardiovascular genetic medicine has undergone rapid changes. Next generation sequencing allows simultaneous testing of all genes associated with any cardiovascular phenotype, and molecular genetic testing for multiple genes has become the standard of practice for cardiovascular medicine. While technical and clinical advantages of multigenic approaches are evident, informed consent procedures have become more complex and challenging to the physician ordering such a test, particularly due to the increased potential for unsolicited findings. Based on the EuroGentest “Guidelines for diagnostic next-generation sequencing” we here propose a set of disease-specific requirements for obtaining informed consent for NGS-based genetic testing in a cardiogenetic clinic. We can show that it is often not feasible to obtain informed consent for every detail and suggest, in such cases, to reach general consent beforehand and discuss specific implications of unsolicited findings after the test results are available.

Informed consent and community engagement in genomic research [PhD THESIS]
Ogunrin, O. A.
University of Liverpool, 2019
Abstract
The introduction of genomic research to, and emergence of biobanks in, sub-Saharan African countries raise ethical issues that require urgent attention. Firstly, there are concerns about whether individuals and communities would agree to participate in this type of research especially considering how communitarianism may affect their decision-making process. Secondly, there are controversies over whether the informed consent process as it is applied to other biomedical researches would be appropriate for genomic research in sub-Saharan Africa. And thirdly, the components of engagement of culturally distinct communities in genomic research are not yet clarified… There was consensus between the adult research participants and the biomedical researchers on the appropriateness of blanket consent type for genomic research but the community leaders, health workers and the youths prefer either reconsenting or delegated consent…

Post-Hong Kong: Human Genome Editing’s Brave New World [VIDEO; 1:33:17]
Wednesday, March 27, 2019 2:00 pm – 3:30 pm; CSIS Headquarters, 2nd Floor
Summary
A firestorm followed Professor He Jiankui’s disturbing announcement last fall in Hong Kong that he had made heritable genetic changes in human embryos that resulted in the birth of twin girls. Critics pointed to the lack of oversight and transparency, the inadequacy of the informed consent process, the lack of a compelling medical rationale, potential unknown future harms to the edited babies, and the lack of a clear consensus about the actual use of new, powerful gene editing technologies. This historic incident has stirred an intense debate over both the promise of these technologies to cure devastating diseases, such as Huntington’s Disease, and alarm over the idea that these same technologies might be used to create “designer babies.” The U.S. National Academy of Sciences and National Academy of Medicine, together with other international academies, have led vital international discussions over next steps.

On Wednesday, March 27, 2:00-3:30 pm, the National Academy of Medicine and the CSIS Commission on Strengthening America’s Health Security [hosted] a conversation on the unfolding debate as to whether human germline genome editing should be permitted, the types of applications which might be appropriate, the standards and criteria that should be followed, and what regulatory or governance framework is needed.

Editor’s Note: In the context of the hour long broadcast by CSIS an audience question related to informed consent and relating to this digest was posed. It was answered by Jeffrey Kahn; Andreas C. Dracopoulos Director, Johns Hopkins Berman Institute of Bioethics, an excerpt of which has been transcribed below. Readers can find this exchange at around 1:20:45 in the broadcast. 

Excerpt
Q – audience member:
Can you talk about some of the therapies that [Editas Medicine] is developing and walk through the informed consent process that would happen in, say for example, childhood blindness? How does that work?

 
A – Jeffrey Kahn; Andreas C. Dracopoulos Director, Johns Hopkins Berman Institute of Bioethics:
I served on the recombinant DNA advisory committee, the so called RAC as Victor mentioned, when the drug that became the Spark Therapeutics drug for treatment of genetic inherited forms of blindness was being considered in its early phase. So that’s the body that reviews gene transfer, so called gene therapy, research in humans. You must get approval from that body advisory to the NIH before you can go forward.

What was really interesting about that particular story which was and is for children, was that the parents of those children, first of all there are no other treatments, there are no alternatives, it was very promising in animal studies and so this is the first time in humans it is being offered. They showed a video I remember very clearly of a child walking through a maze, which was how they set up and assess levels of vision before and after one eye being treated. It was remarkable to watch this child stumble into the obstacles in the before film and then navigate it very easily after.

The question wasn’t so much about whether it should go forward as a clinical trial but whether parents should be permitted to give consent to having both eyes of their children injected at the same time. So the question was, do we know enough about this very novel first in human use of a therapy to say we’re willing to let you risk your child’s vision, because we don’t know the long term effects of this and whether the child’s restored vision would last or plummet and go away after a few weeks.

And the parents said let us make the decision about preserving whatever vision our child may have. The sooner you treat these kids the more vision you preserve it turns out.

What I learned from that was that is not consent in the sense that we really wish for.  There aren’t good alternatives and these parents are willing to do anything for their children to preserve or restore their vision, understandably.

Consent doesn’t work in the way that I think we hope it will in some of these first in human devastating diseases, no other therapy, contexts. People will do anything effectively, so it’s an insufficient tool for doing the ethics work that I think your question implies. I don’t have a good alternative but in lived experience it’s really challenging.

Principles of Regenerative Medicine (Third Edition)
Edited by: Anthony Atala, Robert Lanza, … Robert Nerem
Elsevier, 2019
Chapter 76 – Ethical considerations, RM Green ; Pages 1331-1343
Abstract
Because human stem cells have potential for human development and because they are potent biologic agents, research or clinical translation using them raises many ethical questions. Here I explore eight leading questions: (1) Is it necessary to use human embryos? (2) Is it morally permissible to destroy a human embryo? (3) May one benefit from others’ destruction of embryos? (4) May we create an embryo to destroy it? (5) May we clone human embryos? (6) May we use human stem cells to create chimeras? (7) May we genetically modify human embryos? (8) Are there special considerations governing the use of stem cells in clinical research and clinical applications?