Informed consent and ethical re-use of African genomic data

Rapid advances in human genomic research are increasing the availability of genomic data for secondary analysis. Particularly in the case of vulnerable African populations, ethics and informed consent processes need to be transparent-both to ensure participant protection, as well as to share skills and to evolve best practice for informed consent from a shared knowledge base. An open dialogue between all stakeholders can facilitate this.     

Informed consent and collaborative research: perspectives from the developing world

Introduction: Informed consent has been recognized as an important component of research protocols and procedures of disclosure and consent in collaborative research have been criticized, as they may not be in keeping with cultural norms of developing countries. This study, which is part of a larger project funded by the United States National Bioethics Advisory Commission, explores the opinions of developing country researchers regarding informed consent in collaborative research. Methods: A survey of developing country researchers, involved in human subject research, was conducted by distributing a questionnaire with 169 questions, which included questions relating to informed consent. In addition, six focus group discussions, eight in-depth interviews and 78 responses to open-ended questions in the questionnaire provided qualitative data. Results: 203 surveys were considered complete and were included in the analysis. Written consent was not used by nearly 40% of the researchers in their most recent studies. A large proportion of respondents recommended that human subject regulations should allow more flexibility in ways of documenting informed consent. 84% of researchers agreed that a mechanism to measure understanding should be incorporated in research studies as part of the process of informed consent. Discussion: This paper is an empirical step in highlighting the ethical issues concerning disclosure. Health researchers in developing countries are well aware of the importance of consent in health research, and equally value the significance of educating human subjects regarding study protocols and associated risks and benefits. However, respondents emphasize the need for modifying ethical regulations in collaborative research.     

Informed consent and nudging

In order to avoid patient abuse, under normal situations before performing a medical intervention on a patient, a physician must obtain informed consent from that patient, where to give genuine informed consent a patient must be competent, understand her condition, her options and their expected risks and benefits, and must expressly consent to one of those options. However, many patients refrain from the option that their physician believes to be best, and many physicians worry that their patients make irrational healthcare decisions, hindering their ability to provide efficient healthcare for their patients. Some philosophers have proposed a solution to this problem: they advocate that physicians nudge their patients to steer them towards their physician's preferred option. A nudge is any influence designed to predictably alter a person's behavior without limiting their options or giving them reasons to act. Proponents of nudging contend that nudges are consistent with obtaining informed consent. Here I argue that nudging is incompatible with genuine informed consent, as it violates a physician's obligation to tell their patients the truth, the whole truth, and nothing but the truth during adequate disclosure.     

Informed consent and public health

During the past 25 years, medical ethics has concentrated largely on clinical medicine and the treatment of individual patients. This focus permits a view of medical provision as a (quasi-) consumer good, whose distribution can be or should be contingent on individual choice. The approach cannot be extended to public health provision. Public health provision, including measures for limiting the spread of infectious diseases, is a public good and can be provided for some only if provided for many. The provision or non-provision of public goods cannot be contingent on individual informed consent, so must be in some respects compulsory. An adequate ethics of public health needs to set aside debates about informed consent and to consider the permissible limits of just compulsion for various types of public good. It will therefore gain more from engaging with work in political philosophy than with individualistic work in ethics.     

Informed consent: time for more transparency

Informed consent is not only for documenting a patient's acceptance of enrolling in a clinical trial. It currently is the patient's and, we propose, should also be the public's main source of information regarding the reasons for the planned study, what is known in the field about the proposed trial, and what to expect as far as efficacy and harm. Informed consent is not currently part of the clinical trial registries. For purposes of full disclosure to the patients and the public, the informed consent should be part of the required documents for such registries.     

Informed consent to tissue donation: policies and practice

Nearly 10 years ago, the tissue industry’s informed consent practices with donor families in the United States were criticized. In response, the industry, along with the Inspector General of the Department of Health and Human Services, suggested elements to be included in the informed consent process. This study examines which of these elements were present in the informed consent documents of 45 (78%) of the nation’s 58 Organ Procurement Organizations (OPOs). Some elements, such as involvement of for-profit companies, were present in almost all. Others, such as labeling tissue as a gift from donor families, never were. The authors conclude that the time is ripe for reexamination of the informed consent process with an eye to meaningful consent that promotes the benefits of tissue transplantation and at the same time protects the rights and interests of donor families; can be realistically implemented; and, maintains the trust of the American public.     

Societal preferences for the return of incidental findings from clinical genomic sequencing: a discrete-choice experiment

Background:An important challenge with the application of next-generation sequencing technology is the possibility of uncovering incidental genomic findings. A paucity of evidence on personal utility for incidental findings has hindered clinical guidelines. Our objective was to estimate personal utility for complex information derived from incidental genomic findings.Methods:We used a discrete-choice experiment to evaluate participants’ personal utility for the following attributes: disease penetrance, disease treatability, disease severity, carrier status and cost. Study participants were drawn from the Canadian public. We analyzed the data with a mixed logit model.Results:In total, 1200 participants completed our questionnaire (available in English and French). Participants valued receiving information about high-penetrance disorders but expressed disutility for receiving information on low-penetrance disorders. The average willingness to pay was $445 (95% confidence interval [CI] $322–$567) to receive incidental findings in a scenario where clinicians returned information about high-penetrance, medically treatable disorders, but only 66% of participants (95% CI 63%–71%) indicated that they would choose to receive information in that scenario. On average, participants placed an important value ($725, 95% CI $600–$850) on having a choice about what type of findings they would receive, including receipt of information about high-penetrance, treatable disorders or receipt of information about high-penetrance disorders with or without available treatment. The predicted uptake of that scenario was 76% (95% CI 72%–79%).Interpretation:Most participants valued receiving incidental findings, but personal utility depended on the type of finding, and not all participants wanted to receive incidental results, regardless of the potential health implications. These results indicate that to maximize benefit, participant-level preferences should inform the decision about whether to return incidental findings.Clinical genomic sequencing technologies are on the verge of allowing individualized care at reasonable cost.¹ Patients and their families will soon receive information from clinical sequencing that has implications for clinical care, including information on consequences related to disease prognosis, treatment response or hereditary risk for disease.² Clinical sequencing can also generate incidental findings, which are clinically relevant genetic variants for disorders unrelated to the reason for ordering the genetic testing. The decision of whether to provide information about incidental findings is complex because such results will have varying clinical validity (whether the genetic variant causes the disorder) and utility (whether effective medical treatment is available for the disorder).^3,4 For example, although effective medical treatment may be available for some validated incidental findings, other incidental findings may not be validated as causing the disorder, and still others will be validated but not associated with effective treatment options.To address in part the challenges surrounding the return of incidental findings, the American College of Medical Genetics and Genomics published recommendations for reporting incidental findings from clinical sequencing.⁵ The statement lists a minimum of 56 genes that laboratories should examine, with results reported to patients through the managing physician. This list includes genes with high-penetrance mutations (i.e., a high proportion of individuals with the mutation will exhibit clinical symptoms) validated to be associated with disorders for which medical interventions are available.The original version of this statement did not “favour offering the patient a preference” for which results would be returned. The reasoning was that clinicians have a duty to prevent potential harm by telling patients about incidental findings. The working group that developed the recommendations further stated that it is impractical to provide the level of genetic counselling required for informed preference on all potential disorders.⁵ As such, the working group recommended that clinicians discuss with patients the possibility of receiving incidental findings from the list. It was argued that patient autonomy is preserved because patients can decline clinical sequencing if they prefer to not receive information about incidental findings.⁵ However, this rationale has been subject to debate because of its “all-or-none” nature, whereby patients must agree to receive information about incidental findings or clinical sequencing is not provided.^6–9 In April 2014, in response to the ongoing debate, the statement was amended to include an “opt-out” option for patients who do not want to receive information about incidental findings.¹⁰Notwithstanding the ethical debate, there is a lack of quantitative, preference-based economic evidence for the return of incidental genomic findings.⁸ It has been argued⁸ that this gap in evidence hindered development of the working group’s recommendation statement. More generally, evidence on preferences for the return of incidental findings is crucial for health policy, for health systems planning and for informing future lists that may include “many more genes.”⁸ We aimed to generate evidence on the personal utility that study participants from the Canadian public ascribe to the return of incidental genomic findings in the clinical setting. We chose participants from the general public because the public is the largest stakeholder in Canada’s publicly funded health care system.     

Informed consent procedures: responsibilities of researchers in developing countries

We describe the informed consent procedures in a research clinic in Santiago, Chile, and a qualitative study that evaluated these procedures. The recruitment process involves information, counseling and screening of volunteers, and three or four visits to the clinic. The study explored the decision-making process of women participating in contraceptive trials through 36 interviews. Women understood the research as experimentation or progress. The decision to participate was facilitated by the information provided; time to consider it and to discuss it with partners or relatives; and perceived benefits such as quality of care, non-cost provision of methods and medical care. For some women, participation was an opportunity to express altruism. The main obstacles for participation were perceived side effects or risks. The final risk-benefit balance was strongly influenced by women's needs. Women perceived that the consent form benefited the clinic, proving that participants had made a free decision, and benefited the volunteers by warranting their right to free medical care. The most important problem detected was occasional misunderstanding of the information given on the form. We concluded that a full decision-making process enhances women's ability to exercise their right to choose, and assures research institutions that trials are conducted without coercion and that the participants are committed to the study. Researchers have the responsibility of conducting this process.