Reshaping consent so we might improve participant choice (III) – How is the research participant’s understanding currently checked and how might we improve this process?
Research Article
Hugh Davies, Simon E Kolstoe, Anthony Lockett
Research Ethics, 24 February 2024
Open Access
Abstract
Valid consent requires the potential research participant understands the information provided. We examined current practice in 50 proposed Clinical Trials of Investigational Medicinal Products to determine how this understanding is checked. The majority of the proposals (n = 44) indicated confirmation of understanding would take place during an interactive conversation between the researcher and potential participant, containing questions to assess and establish understanding. Yet up until now, research design and review have not focused upon this, concentrating more on written material. We propose ways this interactive conversation can be documented, and the process of checking understanding improved.

Practical approaches for supporting informed consent in neonatal clinical trials
Mini Review
Susan H. Wootton, Matthew Rysavy, Peter Davis, Marta Thio, Mar Romero-Lopez, Lindsay F. Holzapfel, Tamara Thrasher, Jaleesa D. Wade, Louise Owen
Acta Paediatrica, 22 February 2024
Abstract
The survival and health of preterm and critically ill infants have markedly improved over the past 50  years, supported by well-conducted neonatal research. However, newborn research is difficult to undertake for many reasons, and obtaining informed consent for research in this population presents several unique ethical and logistical challenges. In this article, we explore methods to facilitate the consent process, including the role of checklists to support meaningful informed consent for neonatal clinical trials.
Conclusion
The authors provide practical guidance on the design and implementation of an effective consent checklist tailored for use in neonatal clinical research.

Editor’s note: Acta Paediatrica is a peer-reviewed monthly journal published on behalf of the Foundation Acta Paediatrica based at the Karolinska Institute in Sweden.

The Donation of Human Biological Material for Brain Organoid Research: The Problems of Consciousness and Consent
Masanori Kataoka, Christopher Gyngell, Julian Savulescu, Tsutomu Sawa
Science and Engineering Ethics, 5 February 2024
Abstract
Human brain organoids are three-dimensional masses of tissues derived from human stem cells that partially recapitulate the characteristics of the human brain. They have promising applications in many fields, from basic research to applied medicine. However, ethical concerns have been raised regarding the use of human brain organoids. These concerns primarily relate to the possibility that brain organoids may become conscious in the future. This possibility is associated with uncertainties about whether and in what sense brain organoids could have consciousness and what the moral significance of that would be. These uncertainties raise further concerns regarding consent from stem cell donors who may not be sufficiently informed to provide valid consent to the use of their donated cells in human brain organoid research. Furthermore, the possibility of harm to the brain organoids raises question about the scope of the donor’s autonomy in consenting to research involving these entities. Donor consent does not establish the reasonableness of the risk and harms to the organoids, which ethical oversight must ensure by establishing some measures to mitigate them. To address these concerns, we provide three proposals for the consent procedure for human brain organoid research. First, it is vital to obtain project-specific consent rather than broad consent. Second, donors should be assured that appropriate measures will be taken to protect human brain organoids during research. Lastly, these assurances should be fulfilled through the implementation of precautionary measures. These proposals aim to enhance the ethical framework surrounding human brain organoid research.

Blockchain-Based Dynamic Consent and its Applications for Patient-Centric Research and Health Information Sharing: Protocol for an Integrative Review
Wendy M Charles, Mark B van der Waal, Joost Flach, Arno Bisschop, Raymond X van der Waal, Hadil Es-Sbai, Christopher J McLeod
JMIR Research Protocols, 5 February 2024
Abstract
Background
Blockchain has been proposed as a critical technology to facilitate more patient-centric research and health information sharing. For instance, it can be applied to coordinate and document dynamic informed consent, a procedure that allows individuals to continuously review and renew their consent to the collection, use, or sharing of their private health information. Such has been suggested to facilitate ethical, compliant longitudinal research, and patient engagement. However, blockchain-based dynamic consent is a relatively new concept, and it is not yet clear how well the suggested implementations will work in practice. Efforts to critically evaluate implementations in health research contexts are limited.
Objective
The objective of this protocol is to guide the identification and critical appraisal of implementations of blockchain-based dynamic consent in health research contexts, thereby facilitating the development of best practices for future research, innovation, and implementation.
Methods
The protocol describes methods for an integrative review to allow evaluation of a broad range of quantitative and qualitative research designs. The PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) framework guided the review’s structure and nature of reporting findings. We developed search strategies and syntax with the help of an academic librarian. Multiple databases were selected to identify pertinent academic literature (CINAHL, Embase, Ovid MEDLINE, PubMed, Scopus, and Web of Science) and gray literature (Electronic Theses Online Service, ProQuest Dissertations and Theses, Open Access Theses and Dissertations, and Google Scholar) for a comprehensive picture of the field’s progress. Eligibility criteria were defined based on PROSPERO (International Prospective Register of Systematic Reviews) requirements and a criteria framework for technology readiness. A total of 2 reviewers will independently review and extract data, while a third reviewer will adjudicate discrepancies. Quality appraisal of articles and discussed implementations will proceed based on the validated Mixed Method Appraisal Tool, and themes will be identified through thematic data synthesis.
Results
Literature searches were conducted, and after duplicates were removed, 492 articles were eligible for screening. Title and abstract screening allowed the removal of 312 articles, leaving 180 eligible articles for full-text review against inclusion criteria and confirming a sufficient body of literature for project feasibility. Results will synthesize the quality of evidence on blockchain-based dynamic consent for patient-centric research and health information sharing, covering effectiveness, efficiency, satisfaction, regulatory compliance, and methods of managing identity.
Conclusions
The review will provide a comprehensive picture of the progress of emerging blockchain-based dynamic consent technologies and the rigor with which implementations are approached. Resulting insights are expected to inform best practices for future research, innovation, and implementation to benefit patient-centric research and health information sharing.

Personalized and longitudinal electronic informed consent in clinical trials: How to move the needle?
Evelien De Sutter, Liese Barbier, Pascal Borry, David Geerts, John P.A. Ioannidis, Isabelle Huys
Digital Health, 23 January 2024
Abstract
Changes in the clinical trials landscape have been driven by advancements in digital technology. The use of electronic informed consent to inform research participants and to obtain their consent electronically has the potential to improve participant–researcher interactions over time, facilitate clinical trial participation, and increase efficiency in clinical trial conduct. A personalized electronic informed consent platform that enables long-term interactions with the research team could function as a tool to empower participant engagement in clinical trials. However, significant challenges persist impeding successful and widespread implementation. This Perspective provides insights into the opportunities and challenges for the implementation of electronic informed consent in clinical trials. It sets out key recommendations to promote the implementation of this innovative approach to the informed consent process, including the creation of uniform electronic informed consent platforms at regional and national level.

Participant comprehension and acceptability of enhanced versus text-only electronic informed consent: an innovative qualitative pilot study
Research
Amy Corneli, Summer Starling, Yujung Choi, Jurgis Vosylius, Leanne Madre, Andrew Mackinnon & Pamela Tenaerts
Pilot and Feasibility Studies, 17 January 2024
Open Access
Abstract
Background
The use of electronic informed consent (eIC) in decentralized trials offers a pragmatic approach to enrolling participants across multiple geographic areas.
Methods
Using a randomized, cross-over study design, we conducted a qualitative descriptive evaluation of two eIC approaches—text-only eIC and enhanced eIC—in a mock hypertension Phase III clinical trial. We assessed participant comprehension and acceptability (usability, satisfaction, and eIC preference).
Results
A total of 24 individuals with hypertension participated in the study: 12 reviewed the text-only eIC first, followed by the enhanced eIC, and 12 reviewed the enhanced eIC first, followed by the text-only eIC. The study population was diverse in gender, age, race, and geographic location. We found no descriptive differences in participant comprehension and satisfaction between the two eIC approaches. However, more participants preferred the enhanced eIC, and participants indicated that the digital elements were personable and made them feel more informed, engaged, comfortable, and prepared to participate in clinical research.
Conclusions
Our findings suggest that enhancing the eIC process with digital elements may have beneficial outcomes among potential participants beyond comprehension and satisfaction.

Stakeholders’ perspectives on clinical trial acceptability and approach to consent within a limited timeframe: a mixed methods study
Original Research
Elizabeth Deja, Chloe Donohue, Malcolm G Semple, Kerry Woolfall
BMJ Open, 2 January 2023
Abstract
Objectives
The Bronchiolitis Endotracheal Surfactant Study (BESS) is a randomised controlled trial to determine the efficacy of endo-tracheal surfactant therapy for critically ill infants with bronchiolitis. To explore acceptability of BESS, including approach to consent within a limited time frame, we explored parent and staff experiences of trial involvement in the first two bronchiolitis seasons to inform subsequent trial conduct
Design
A mixed-method embedded study involving a site staff survey, questionnaires and interviews with parents approached about BESS.
Setting
Fourteen UK paediatric intensive care units.
Participants
Of the 179 parents of children approached to take part in BESS, 75 parents (of 69 children) took part in the embedded study. Of these, 55/69 (78%) completed a questionnaire, and 15/69 (21%) were interviewed. Thirty-eight staff completed a questionnaire.
Results
Parents and staff found the trial acceptable. All constructs of the Adapted Theoretical Framework of Acceptability were met. Parents viewed surfactant as being low risk and hoped their child’s participation would help others in the future. Although parents supported research without prior consent in studies of time critical interventions, they believed there was sufficient time to consider this trial. Parents recommended that prospective informed consent should continue to be sought for BESS. Many felt that the time between the consent process and intervention being administered took too long and should be ‘streamlined’ to avoid delays in administration of trial interventions. Staff described how the training and trial processes worked well, yet patients were missed due to lack of staff to deliver the intervention, particularly at weekends.
Conclusion
Parents and staff supported BESS trial and highlighted aspects of the protocol, which should be refined, including a streamlined informed consent process. Findings will be useful to inform proportionate approaches to consent in future paediatric trials where there is a short timeframe for consent discussions.

Participants’ understanding of informed consent in clinical trials: A systematic review and updated meta-analysis
Chengai Wu, Na Wang, Qianqian Wang, Chao Wang, Zhenjie Wei, Zhimin Wu, Shunan Yu, Xieyuan Jiang
PLOS One, 2 January 2024
Open Access
Abstract
Obtaining written informed consent from participants before enrolment in a study is essential. A previous study showed that only 50% of the participants in clinical trials understood the components of informed consent, and the methods of participants’ understanding of informed consent were controversial. This updated meta-analysis aimed to estimate the proportion of participants in clinical trials who understand the different informed consent components. PubMed, EMBASE, the Cochrane Library, and Scopus were searched till April 2023. Therapeutic misconception, ability to name one risk, knowing that treatments were being compared, and understanding the nature of the study, the purpose of the study, the risks and side-effects, the direct benefits, placebo, randomization, voluntariness, freedom to withdraw, the availability of alternative treatment if withdrawn from the trial, confidentiality, compensation, or comprehension were evaluated. This meta-analysis included 117 studies (155 datasets; 22,118 participants). The understanding of the risks and side-effects was investigated in the largest number of studies (n = 100), whereas comprehension was investigated in the smallest number (n = 11). The highest proportions were 97.5%(95% confidence interval (CI): 97.1–97.9) for confidentiality, 95.9% (95% confidence interval (CI): 95.4–96.4) for compensation, 91.4% (95% CI: 90.7–92.1) for the nature of study, 68.1% (95% CI: 51.6–84.6) for knowing that treatments were being compared, and 67.3% (95% CI: 56.6–78) for voluntary nature of participants. The smallest proportions were the concept of placebo (4.8%, 95%CI: 4.4–5.2) and randomization(39.4%, 95%CI: 38.3–40.4). Our findings suggested that most participants understood the fundamental components of informed consent (study confidentiality, nature, compensation, voluntariness, and freedom to withdraw). The understanding of other components, such as placebo and randomization was less satisfactory.

Testing and Practical Implementation of a User-Friendly Personalized and Long-Term Electronic Informed Consent Prototype in Clinical Research: Mixed Methods Study
Evelien De Sutter, David Geerts, Koen Yskout, Stef Verreydt, Pascal Borry, Liese Barbier, Isabelle Huys
Journal of Medical Internet Research, 19 December 2023
Abstract
Background
Over the years, there has been increasing interest in electronic informed consent (eIC) in clinical research. The user-friendliness of an eIC application and its acceptance by stakeholders plays a central role in achieving successful implementation.
Objective
This study aims to identify insights for the design and implementation of a user-friendly, personalized, and long-term eIC application based on a usability study with (potential) research participants and semistructured interviews with stakeholders on the practical integration of such an application into their daily practice.
Methods
An eIC prototype was evaluated and refined through usability testing among Belgian citizens and iterative redesign. On the basis of a digital literacy questionnaire, a heterogeneous sample of participants was established. Participants needed to complete a series of usability tasks related to personalization and long-term interaction with the research team while using the “think aloud” technique. In addition, usability tests involved completing the System Usability Scale questionnaire and taking part in a semistructured feedback interview. Furthermore, semistructured interviews were conducted with ethics committee members, health care professionals, and pharmaceutical industry representatives active in Belgium and involved in clinical research. Thematic analysis was undertaken using the NVivo software (Lumivero).
Results
In total, 3 iterations of usability tests were conducted with 10 participants each. Each cycle involved some participants who reported having low digital skills. The System Usability Scale scores related to the tasks on personalization and long-term interaction increased after each iteration and reached 69.5 (SD 8.35) and 71.3 (SD 16.1) out of 100, respectively, which represents above-average usability. Semistructured interviews conducted with health care professionals (n=4), ethics committee members (n=8), and pharmaceutical industry representatives (n=5) identified the need for an eIC system that can be easily set up. For example, a library could be established enabling stakeholders to easily provide background information about a clinical study, presented in the second layer of the interface. In contrast, some functionalities, such as informing participants about new studies through an eIC system, were not considered useful by stakeholders.
Conclusions
This study provides insights for the implementation of a user-friendly personalized and long-term eIC application. The study findings showed that usability testing is key to assessing and increasing the user-friendliness of an eIC application. Although this eIC system has the potential to be usable by a wide audience, participants with low digital literacy may not be able to use it successfully, highlighting the need for additional support for participants or other alternatives to an eIC system. In addition, key lessons emerging from the interviews included ensuring that the application is easy to implement in practice and is interoperable with other established systems.

Opportunities to Advance Equity Through Informed Consent Discussions
Invited Commentary
Puja J. Umaretiya, Emily E. Johnston
JAMA Network Open, 11 December 2023; 6(12)
Excerpt
As pediatric oncologists, we often ask parents to do the unthinkable: grapple with a child’s new cancer diagnosis and participate in a clinical trial informed consent discussion within hours to days of each other. Informed consent is essential to our practice because access to clinical trials is the standard of care in pediatric oncology. These discussions are both emotionally charged and medically complex, adding challenges to effective communication. Nearly 2 decades ago, Kodish and colleagues first examined this process in a cohort of parents consenting to therapeutic trials for children with newly diagnosed acute leukemia and found that only one-third of parents understood the concept of randomization and that non–English-speaking families were less likely than English-speaking families to understand key aspects of informed consent. Since then, our trials and informed consent discussions have become more complex. Aristizabal et al found that these gaps in our informed consent process persist, particularly for historically marginalized groups exposed to adverse social determinants of health…

Editor’s Note: The text of the commentary does not reference assent or the involvement of pediatric patient in consent processes.