Ethical tensions in the informed consent process for randomized clinical trials in emergency obstetric and newborn care in low and middle-income countries
Debate
Dan K. Kaye, Gershom Chongwe, Nelson K. Sewankambo
BMC Medical Ethics, 27 April 2019; 20(27)
Abstract
Background
There is unanimous agreement regarding the need to ethically conduct research for improving therapy for patients admitted to hospital with acute conditions, including in emergency obstetric care. We present a conceptual analysis of ethical tensions inherent in the informed consent process for randomized clinical trials for emergency obstetric care and suggest ways in which these could be mitigated.
Discussion
A valid consenting process, leading to an informed consent, is a cornerstone of this aspect necessary for preservation and maintenance of respect for autonomy and dignity. In emergency obstetric care research, obtaining informed consent can be problematic, leading to ethical tension between different moral considerations. Potential participants may be vulnerable due to severity of disease, powerlessness or impaired decisional capacity. Time for the consent process is limited, and some interventions have a narrow therapeutic window. These factors create ethical tension in allowing potentially beneficial research while avoiding potential harms and maintaining respect for dignity, human rights, justice and autonomy of the participants.
Conclusion
Informed consent in emergency obstetric care in low- and middle-income countries poses numerous ethical challenges. Allowing research on vulnerable populations while maintaining respect for participant dignity and autonomy, protecting participants from potential harms and promoting justice underlie the ethical tensions in the research in emergency obstetric and newborn care. Those involved in research conduct or oversight have a duty of fair inclusion, to avoid denying participants the right to participate and to any potential research benefits.

Reporting of ethical approval and informed consent in clinical research published in leading nursing journals: a bibliometric analysis
Wu, Y, Howarth, ML, Zhou, C and Cong, W
BMC Medical Ethics, 10 May 2019
Abstract
Background
Ethical considerations play a prominent role in the protection of protect human subjects in clinical research. To date the disclosure of ethical protection in clinical research published in the international nursing journals has not been explored. Our research objective was to investigate the reporting of ethical approval and informed consent in clinical research published in leading international nursing journals.
Methods
We used a research based on bibliometric analysis. All clinical research published in the five leading international nursing journals from the SCI Journal Citation Reports (2017 version) between 2015 and 2017 were retrieved to evaluate for evidence of ethical review.
Results
A total of 2041 citations have been identified from the contents of all the five leading nursing journals that were published between 2015 and 2017. Out of these, 1284 clinical studies have been included in the text to extract the data of ethical review. From these, a total of 87.5% of prospective clinical studies mentioned informed consent. Only 52.9% of those reported that written informed consent had been obtained;3.6% reported oral consent, and 6.8% used other ways such as online consent or completion and return of data collection (such as surveys) to denote assent. Notably, 36.2% of those did not describe the method used to obtain informed consent and merely described that “consent was obtained from participants or participants agreed to join in the research”. Furthermore, whilst 93.7% of clinical studies mentioned ethical approval; 92.5% of those stated the name of ethical committee and interestingly, only 37.1% of those mentioned the ethical approval reference. The rates of reporting ethical approval were different between different study type, country, and whether mentioning financial support (all P<0.05). In addition, positive statistically significant correlations were found between reporting informed consent, reporting written informed consent, reporting ethical approval, naming of ethical committee, and reporting ethical approval reference number in the five leading international nursing journals (all P<0.01).
Conclusion
The reporting of ethics in leading international nursing journals demonstrates progress but improvement of the transparency and the standard of ethical reporting in nursing clinical research is required.

Comprehension and recall from the informed consent process by phase I healthy volunteers before dose administration
Research Article
Rami Tadros, Gillian E Caughey, Sally Johns, Sepehr Shakib
Clinical Trials, 28 February 2019; 16(3)
Abstract
Aims/Background
A fundamental part of all clinical trials is informed consent, reflecting the respect for the volunteer’s autonomy. Research participation is voluntary; therefore, certain aspects of the proposed study must be disclosed so that volunteers can make an informed decision. In this study, we aimed to examine the level of comprehension and recall of healthy volunteers from the informed consent process.
Methods
The study was carried out at a single phase I clinical trials unit. A questionnaire was administered to each volunteer to assess recall of important aspects of the study at the day-1 visit following the informed consent process. The questionnaire contained seven questions regarding study objectives, route, frequency and type of drug administration, adverse effects, number of subjects previously exposed and remuneration. One point was awarded for each correct answer.
Results
A total of 266 volunteers were administered the questionnaire. The mean total score (±standard deviation) for all volunteers was 4.5 ± 1.1 points out of 7, with a range of 0.8–6.7. For all 10 studies, 91% of volunteers responded correctly when answering about the route of administration, and 90% were able to accurately state the correct payment amount. Only 7% were able to repeat the aims of the study correctly.
Conclusion
The poor performance of our study volunteers raises concerns about recall of information prior to study drug administration. This has implications for the volunteer’s safety and ability to provide true informed consent. Interventions to improve recall prior to dosing should be undertaken.

Consent complexities, Ebola, and the fine line between collaboration and exploitation in research conducted during public health emergencies [KEYNOTE]
Nouvet, Elysée
PREA Conference. Ethics and Humanitarian Research: Generating Evidence Ethically. The Fawcett Event Center, The Ohio State University, Columbus, Ohio, March 25-26, 2019. Presentation. Session 9. Keynote 3.
Abstract
Background
There is significant and growing scholarship attending to the experiences and motivations of clinical Tx trial participants in Low and Middle Income Countries (LMICs). A smaller and newer body of research is emerging around perceptions and experiences of research conducted during public health emergencies. This presentation is based on one such Research on Research (RoR) study, the R2HC-funded qualitative study “Perceptions and moral experiences of research conducted during the 2014-16 West Africa Ebola outbreak.”
Objective
This presentation takes West Africans’ first-hand accounts of decisions to support or enroll in EVD research as a point of departure for troubling normative parameters and markers of “consent to research”.
Methodology
Content for this presentation is based on team-based analysis of semi-structured interviews (N=99) with West African EVD study participants, members of research ethics boards, researchers, trial staff, and community leaders.
Findings
Our interviews revealed diverse motivations and aspirations or participating or supporting trials, as well as some frustrations around limited options for engagement and impact. A number of researchers with whom we spoke experienced their decisions to “collaborate” on trials as coerced. Others – participants and community leaders – evidently embraced opportunities to enroll in and/or support trials, but simultaneously connected their voluntariness to conviction of their participation’s impact on lives, to understandings of collective ownership over bio-samples, and/or to hopes for new political subjectivities. Mismatch between consent to trials (where consent includes both enrollment in or collaboration with) and the loaded significances of that consent for many with whom we spoke indicate a need for more localized and critical attention to the logics and significances of consent to research in particular humanitarian emergencies.
Conclusion
Upholding ideals of free and informed consent to research in contexts such as ETCs, where those approached for research are sick, distressed, and quarantined, is never going to be easy. What our research flags is that the complexities of consent during the West Africa EVD epidemic extended beyond the walls of the ETC and beyond infected patients. This in turn supports broadening what normally gets included in discussion of and strategies to uphold consent and voluntariness in humanitarian heath emergency research.

When Is It Ethical for Physician-Investigators to Seek Consent From Their Own Patients?
Stephanie R. Morain, Steven Joffe, Emily A. Largent
The American Journal of Bioethics, 17 April 2019; 19(4) pp 11-18
Abstract
Classic statements of research ethics advise against permitting physician-investigators to obtain consent for research participation from patients with whom they have preexisting treatment relationships. Reluctance about “dual-role” consent reflects the view that distinct normative commitments govern physician–patient and investigator–participant relationships, and that blurring the research–care boundary could lead to ethical transgressions. However, several features of contemporary research demand reconsideration of the ethics of dual-role consent. Here, we examine three arguments advanced against dual-role consent: that it creates role conflict for the physician-investigator; that it can compromise the voluntariness of the patient-participant’s consent; and that it promotes therapeutic misconceptions. Although these concerns have merit in some circumstances, they are not dispositive in all cases. Rather, their force—and the ethical acceptability of dual-role consent—varies with features of the particular study. As research participation more closely approximates usual care, it becomes increasingly acceptable, or even preferable, for physicians to seek consent for research from their own patients. It is time for a more nuanced approach to dual-role consent.

Ethical tensions in the informed consent process for randomized clinical trials in emergency obstetric and newborn care in low and middle-income countries
Dan K. Kaye, Gershom Chongwe, Nelson K. Sewankambo
BMC Medical Ethics, 27 April 2019; (20)27
Abstract
Background
There is unanimous agreement regarding the need to ethically conduct research for improving therapy for patients admitted to hospital with acute conditions, including in emergency obstetric care. We present a conceptual analysis of ethical tensions inherent in the informed consent process for randomized clinical trials for emergency obstetric care and suggest ways in which these could be mitigated.
Discussion
A valid consenting process, leading to an informed consent, is a cornerstone of this aspect necessary for preservation and maintenance of respect for autonomy and dignity. In emergency obstetric care research, obtaining informed consent can be problematic, leading to ethical tension between different moral considerations. Potential participants may be vulnerable due to severity of disease, powerlessness or impaired decisional capacity. Time for the consent process is limited, and some interventions have a narrow therapeutic window. These factors create ethical tension in allowing potentially beneficial research while avoiding potential harms and maintaining respect for dignity, human rights, justice and autonomy of the participants.
Conclusion
Informed consent in emergency obstetric care in low- and middle-income countries poses numerous ethical challenges. Allowing research on vulnerable populations while maintaining respect for participant dignity and autonomy, protecting participants from potential harms and promoting justice underlie the ethical tensions in the research in emergency obstetric and newborn care. Those involved in research conduct or oversight have a duty of fair inclusion, to avoid denying participants the right to participate and to any potential research benefits.

Editor’s note: The authors mentions sub-Sharan Africa as an example of the LMICs they are referring to in this article.

Informed Consent in IBD Trials: Where We Are and Where We Need to Go
Michael Kurin, Jeffry Katz, Eric Kodish, Bret Lashner
Inflammatory Bowel Diseases, 16 April 2019
Abstract
Patient enrollment is increasingly recognized as a major limiting factor to inflammatory bowel disease (IBD) clinical trial completion. Many IBD trials will fail to enroll enough patients to adequately power their study. This has led to a renewed multifaceted effort to encourage more patients to enroll in clinical trials. Although this is of clear importance, it is also important to ensure that all efforts to enroll patients in clinical trials do not compromise the quality and validity of the patient’s/study participant’s informed consent. Informed consent has 4 components: disclosure, voluntariness, understanding, and capacity. The application of informed consent to IBD clinical trials for biologic agents has not been previously studied. Yet the nature of clinical trials for biologics in IBD creates certain challenges to properly fulfilling the requirements of informed consent in the recruitment process that should be examined. In the following commentary, the components of informed consent are reviewed, challenges to their fulfillment in IBD trials are reviewed, and practical advice is offered.

Will Shorter Informed Consent Forms with Visual Aids Improve Understanding of the Document in Adult and Elderly Populations of Clinical Trials?
Bloswick, Agata, Skowron, Agnieszka
Ethics & Medicine, Spring 2019; 35(1) pp 43-44
Abstract
The informed consent form (ICF) is a critical document for ensuring patients are properly informed about participation in clinical trials, yet there are no regulations that govern the length and format of the document, for the texts reach an average length of 18 pages. The aim of the present study is to conduct a readability assessment, comparing a standard version ICF of 18 pages and a modified (shortened to 11 pages and illustrated) version ICF, using the methodology for the approval of patient information leaflets for marketed medications mandated in Poland and assessing two age groups—adults aged 18-65 and elderly >65. Ten adult and 10 elderly participants were included in the study.

The long and short versions of the ICF resulted in different reading speeds in the adult group; the long version was read 75% faster than the short one on a words-per-minute basis, suggesting a less-thorough reading of the longer text. The difference in information retention, measured by a follow-up questionnaire, was over 20% better recall of risks, procedures, and benefits by the adult group readers of the short ICF.

In the elderly group of participants, the retention and understanding of the documents was significantly lower overall (50% fewer correct answers in comparison to the adult group). In contrast to the adult group, the words-per-minute reading speed for the shorter version was 50% greater than for the longer. The elderly readers appeared to have reviewed the longer document more thoroughly while skipping the tabularized elements of the shortened document that were intended to simplify key information. A detailed analysis shows that the documents with visual aids were less effective for the elderly than plain text.

Based on the information retention observed in this study, significant improvements in readability and design are needed for informed consent forms to fulfill their intended purpose.

Informed Consent in Biomedical Research
Fida K.Dankar, MartonGergely, SamarDankar
Computational and Structural Biotechnology Journal, 25 March 2019
Abstract
Informed consent is the result of tumultuous events in both the clinical and research arenas over the last 100 years. Throughout this time, the notion of informed consent has shifted tremendously, both due to advances in medicine, as well as the type of data being gathered. As such, informed consent has misaligned with the goals of medical research. It is becoming more and more vital to address this chasm, and begin building new frameworks to link this disconnect. Thus, we address three goals in this paper. First, we discuss the history of informed consent and unify the varying definitions of the term. Second, we evaluate the current research on the topic, classify them into themes, and attend to the problems therein. Lastly, we employ these themes of informed consent research mentioned previously to provide guidance and insight for future research in the arena.