Informed Consent for Potential Recipients of Pig Kidney Xenotransplantation in the United States
Luz A. Padilla. Daniel Hurst, Kathryn Maxwell, Kennan Gawlowicz Wayne Paris, David Cleveland, David K.C. Cooper
Transplantation, 27 April 2022
Abstract
Clinical trials of kidney xenotransplantation are being considered in the United States. Before this novel procedure can take place, investigators will have to obtain approval from the institutional review board. The consent form that will be used for such a trial and that will receive approval from the institutional review board will be complex. Informed consent—the process by which a research participant provides his/her permission to participate in a clinical trial—is a staple of the research process and most commonly is in the form of a physical document. In the case of a novel procedure with uncertain benefits and risks and a participant population in acute need of a transplant, the consent process is crucial. These complexities may raise several ethical considerations for the initial pig kidney xenotransplantation recipients in the United States that will require adaptations of the required elements of the informed consent process by the US Department of Human and Health Services. The ethical issues include (1) a subject’s ability to withdraw from the trial, (2) restrictions on their reproductive rights, and (3) the possibility of the need for quarantine if there is a perceived risk of xenozoonosis. This article aims to discuss ethical considerations that may challenge the general required elements of the informed consent form stipulated by the 45 Code of Federal Regulations 46 of the US Department of Health and Human Services and to suggest recommendations for deliberation.

Improving Consent and Response in Longitudinal Studies of Aging: Proceedings of a Workshop
Brian Harris-Kojetin
Improving Consent and Response in Longitudinal Studies of Aging: A Workshop, 25 March 2022
National Academies of Sciences, Engineering, and Medicine; Division of Behavioral and Social Sciences and Education; Committee on National Statistics
Excerpt
This Proceedings of a Workshop summarizes the presentations and discussions at the Workshop on Improving Consent and Response in Longitudinal Studies of Aging, which was held virtually and live-streamed on September 27-28, 2021. The workshop was convened by the Committee on National Statistics of the National Academies of Science, Engineering, and Medicine to assist the National Institute on Aging (NIA) with its methodological research agenda and inform the different longitudinal survey programs sponsored by NIA about practices and research to improve response and consent in other survey programs. The workshop was structured to bring together scientists and researchers from multiple disciplines and countries to share their research and insights on how to improve response and consent in large, representative longitudinal studies on aging.

Experimenting with modifications to consent forms in comparative effectiveness research: understanding the impact of language about financial implications and key information
Research
Nyiramugisha K. Niyibizi, Candace D. Speight, Gabriel Najarro, Andrea R. Mitchell, Ofer Sadan, Yi-An Ko, Neal W. Dickert
BMC Medical Ethics, 27 March 2022; 23(34)
Open Access
Abstract
Background
Informed consent forms are intended to facilitate research enrollment decisions. However, the technical language in institutional templates can be unfamiliar and confusing for decision-makers. Standardized language describing financial implications of participation, namely compensation for injury and costs of care associated with participating, can be complex and could be a deterrent for potential participants. This standardized language may also be misleading in the context of comparative effectiveness trials of standard care interventions, in which costs and risk of injury associated with participating may not differ from regular medical care. In addition, the revised U.S. Common Rule contains a new requirement to present key information upfront; the impact of how this requirement is operationalized on comprehension and likelihood of enrollment for a given study is unknown.
Methods
Two online surveys assessed the impact of (1) changes to compensation for injury language (standard vs. tailored language form) and (2) changes to the key information page (using the tailored compensation language form with standard key information vs. modified key information vs. modified key information plus financial information) on both likelihood of enrollment in and understanding of a hypothetical comparative effectiveness trial.
Results
Likelihood of enrolling was not observed to be different between the standard and tailored language forms in Study 1 (73 vs. 75%; p = 0.6); however, the tailored language group had a higher frequency of understanding the compensation for injury process specific to the trial (25 vs. 51%; p < 0.0001). Modifications to the key information sheet in Study 2 did not affect likelihood of enrolling (88 vs. 85 vs. 85%; p = 0.6); however, understanding of randomization differed by form (44 vs. 59 vs. 46%; p = 0.002).
Conclusions
These findings suggest that refining consent forms to clarify key information and tailoring compensation for injury language to the nature of the study, especially in the context of comparative effectiveness trials, may help to improve study comprehension but may not impact enrollment.

Obtaining Informed Consent for Research Studies
Book Chapter
Lynne M. Bianchi
Research during Medical Residency, 2022 [Taylor & Francis]
Abstract
This chapter describes how to communicate the information included in our institutional review board-approved consent form in an effective and appropriate manner to optimize comprehension and minimize undue influence and coercion. Effective communication involves more than simply reading the form to someone. Informed consent requires that potential participants are given the required information and sufficient time to decide whether they wish to join a study. The informed consent document and conversations include discussion of the voluntary nature of participation, the study purpose, methods, duration, risks, benefits, confidentiality of records, contact information for questions or concerns. Whether investigator- or participant-initiated withdrawal, if there are treatments, protocols, or follow-up appointments required to protect the well-being of the participant upon study withdrawal, those are explained in the consent form and reviewed during informed consent conversations. A parent or legally authorized representative grants the consent for the individual to participate.

Evaluating models of consent in changing health research environments
Scientific Contribution
Svenja Wiertz, Joachim Boldt
Medicine, Health Care and Philosophy, 14 March 2022
Open Access
Abstract
While Specific Informed Consent has been the established standard for obtaining consent for medical research for many years, it does not appear suitable for large-scale biobank and health data research. Thus, alternative forms of consent have been suggested, based on a variety of ethical background assumptions. This article identifies five main ethical perspectives at stake. Even though Tiered Consent, Dynamic Consent and Meta Consent are designed to the demands of the self-determination perspective as well as the perspective of research as a public good, they are still also criticized from both perspectives. In addition, criticisms based on concerns of justice, participation and democratic deliberation, and relational concerns have been levelled at each of the models. As all of these perspectives have valid points to make, the task at hand lies in balancing these ethical perspectives. What constitutes an adequate balancing depends on contextual factors. These factors include digital infrastructure and digital literacy, data safety regulation, good scientific and clinical practice, transparent debates on ethically relevant features of research, social inequalities, anti-discrimination laws and practices, trust in health care institutions and recognition of patient preferences, and consensus on unethical research. We argue that the role of context in determining acceptable models of consent puts the ethical importance of models of consent into perspective. Since altering contextual factors can help to live up to the ethical concerns at stake in debates about models of consent, opting for such a shift of focus comes without ethical loss.

Four reasons why too many informed consents to clinical research are invalid: a critical analysis of current practices
Communication
Anne Wisgalla, Joerg Hasford
BMJ Open – Ethics, 4 March 2022
Open Access
Abstract
Objective
Informed consent (IC) is a central ethical and legal requirement for clinical research that aims to protect the autonomy of participants. To enable an autonomous decision and valid consent, adequate understanding must be ensured. However, a considerable proportion of participants do not understand the relevant aspects about participation in research, for example, approximately 45% could not name at least one risk. As such, the inadequate understanding of IC has been known for several decades, and it still constitutes a severe problem for the ethical conduct of research. Through delineating the most pressing deficits of current IC procedures that lead to insufficient understanding, we aim to encourage the discussion among stakeholders, for example, clinical researchers, and to provide the grounds for practical solutions.
Main arguments
(1) IC documents are too long to be read completely, thus, make it very difficult for potential participants to identify the material facts about the trial. (2) The low readability of the IC documents disadvantages persons with limited literacy. (3) The therapeutic misconception frequently prevents participants to realise that the primary purpose of clinical research is to benefit future patients. (4) Excessive risk disclosures, insufficient information about expected benefits and framing effects compromise a rational risk/benefit assessment.
Conclusion
Due to these deficits, practices of IC in clinical research too often preclude adequate understanding of prospective participants, thus, invalidating IC. The gap between the well-specified ethical norm to enable IC and its insufficient translation into practice can no longer be accepted, as participant rights and the public trust in responsible research are at stake. Hence, immediate action is needed to address the prevailing deficits.

Streamlined versus traditional consent for low-risk comparative effectiveness trials: a randomized experimental study to measure patients’ and public attitudes
Research Article
Nancy E Kass, Ruth R Faden, Stephanie R Morain, Kristina Hallez, Rebecca A Stametz, Amanda R Milo, Deserae Clarke
Journal of Comparative Effectiveness Research, 3 March 2022
Abstract
Aim
Streamlining consent for low-risk comparative effectiveness research (CER) could facilitate research, while safeguarding patients’ rights.
Materials & methods
2618 adults were randomized to one of seven consent approaches (six streamlined and one traditional) for a hypothetical, low-risk CER study. A survey measured understanding, voluntariness, and feelings of respect.
Results
Participants in all arms had a high understanding of the trial and positive attitudes toward the consent interaction. Highest satisfaction was with a streamlined approach showing a video before the medical appointment. Participants in streamlined were more likely to mistakenly think a signature was required.
Conclusion
Streamlined consent was no less acceptable than traditional, signed consent. Streamlined and traditional approaches achieved similar levels of understanding, voluntariness and a feeling that the doctor–patient interaction was respectful.

Getting the Most out of Consent: Patient-Centered Consent for an Acute Stroke Trial
Article
Neal W. Dickert, Kathleen Metz ,S. Iris Deeds, Michael J. Linke, Andrea R. Mitchell, Candace D. Speight, Opeolu M. Adeoye
Ethics & Human Research, 26 February 2022
Abstract
Informed consent for clinical trials in acute stroke is characterized by challenges related to urgency, cognitive impairment, and geographical separation. Context-appropriate approaches are needed for this setting. We conducted a mixed-methods project involving focus groups and interviews as well as collaboration with a patient advisory panel and a central institutional review board (CIRB) to design and implement a patient-driven consent process for a multicenter trial incorporating adaptive randomization. Remote consent was recognized as challenging but acceptable. Adaptive randomization was viewed positively, but significant potential for misunderstanding was appreciated. Collaboration between the patient advisory panel and the CIRB resulted in a shortened, more patient-centered consent form that was approved at all sites with few modifications. An information sheet was developed as a resource for patients and surrogates after enrollment. Collaboration between investigators, patient partners, and a CIRB can facilitate innovation and implementation of patient-centered, context-appropriate consent strategies.

Reshaping the review of consent so we might improve participant choice
Research Article
Hugh Davies
Research Ethics, 15 September 2021
Abstract
Consent is one necessary foundation for ethical research and it’s one of the research ethics committee’s major roles to ensure that the consent process meets acceptable standards. Although on Oxford ‘A’ REC (an NHS Research Ethics Committee based in the UK) we’ve been impressed by the thought and work put into this aspect of research ethics, we’ve continued to have concerns about the suitability and effectiveness of consent processes in supporting decision making, particularly for clinical trials. There’s poor understanding of what people want to help them decide; current processes don’t provide the best grounding for informed consent and there’s inadequate public involvement. We’ve also found a lack of proportionality with researchers failing to adapt consent procedures in proportion to the burdens and consequences of the study. As a result, people are often not best helped to make an informed choice when asked to join a research study. To address these concerns, we considered how we might improve this aspect of research ethics review. Recognising the central importance of the dialogue between the volunteer and researcher, we’ve drawn up a model or flowchart of what we deem good consent practice, proposing consent should be built around four simple steps:

Step 1: Introducing the study and the choices: helping the potential participants get an overview of the proposal and introducing the key issues.

Step 2: Explaining all the details of the study using the detailed Participant Information Sheet.

Step 3: After a gap, if necessary, reviewing and checking understanding.

Step 4: Reaching agreement and recording consent.

These steps, we believe, could help all involved and this article lays out ways we might improve participant choice while complying with accepted principles and current regulations.

Evaluation of a blockchain-based dynamic consent platform (METORY) in a decentralized and multicenter clinical trial using virtual drugs
Ki Young Huh, Seol Ju Moon, Sang-Un Jeong, Min-Ji Kim, Wooseok Yang, Myeonggyu Jeong, Min-Gul Kim, SeungHwan Lee
Clinical and Translational Science, 14 February 2022
Abstract
Blockchain is a novel data architecture characterized by a chronological sequence of blocks in a decentralized manner. We aimed to evaluate the real-world feasibility of a blockchain-based dynamic consent platform (METORY) in a decentralized and multicenter trial. The study consisted of three visits (i.e., screening and 2 follow-up visits) with a 2-week interval. Each subject was required to report the self-measured body temperatures and take a virtual investigational drug by entering the unique drug code on the application. To simulate real-world study settings, two major (i.e., changes in the schedule of body temperature measurement) and three minor protocol amendments (i.e., nonsignificant changes without any changes in the procedures) were set. Overall study completion rates, proportion of consent, and response time to each protocol amendment and adherence were evaluated. A total of 60 subjects (30 in each center) were enrolled in two study centers. All subjects completed the study, and the overall proportion of consent to each protocol amendment was 95.7 ± 13.7% (mean ± SD), with a median response time of 0.2 h. Overall, subjects took 90.8% ± 19.2% of the total drug, whereas compliance with the schedule was 69.1% ± 27.0%. Subjects reported 96.7% ± 4.2% of the total body temperature measurements whereas the adherence to the schedule was 59.0% ± 25.0%, which remarkably decreased after major protocol amendments. In conclusion, we evaluated a blockchain-based dynamic consent platform in real clinical trial settings. The results suggested that major changes should be avoided unless subjects’ proper understanding is warranted.