Xenotransplantation and Informed Consent
Book Chapter
Daniel J. Hurst
Xenotransplantation, 22 June 2023 [Springer]
Abstract
Xenotransplantation (XTx; particularly, pig-to-human transplant) clinical trials of solid organs are likely on the horizon. There is a rich literature noting ethical issues that are particular to XTx clinical trials. Because of these ethical particularities and peculiarities, the informed consent process for XTx has been seen by some commentators as a very challenging endeavor. While organ transplant appears to be on the verge of a wave of XTx clinical trials, it can be surprising that more recent standardized guidance on proper informed consent for these trials is largely missing from the literature. This chapter provides an overview of where the major debates in XTx informed consent lay and attempts to provide some clarity for a way forward.

Who owns your consent? How REBs give away participants’ agency
Janice Aurini, Vanessa Iafolla
Research Ethics, 14 June 2023
Abstract
We draw on three illustrative vignettes to examine how REBs manage participants’ agency in the context of qualitative research. We ask: Who owns a participant’s consent? Central to informed consent is the principle of Respect for Persons, which privileges the autonomy of individuals to make decisions about what happens (or not) to them. Yet, REBs sometimes require researchers to get permission from organizations to conduct research on their current and former members, even when the research is not about those organizations. Our aim is to raise awareness about the inherent contradictions of this practice and to consider guidelines for determining the appropriateness of involving organizations that may be tangentially connected to the research objectives or potential participants.

Editor’s note: REB in the abstract above refers to a research ethics board.

Reshaping consent so we might improve participant choice (II) – helping people decide
Research Article
Hugh Davies, Rosie Munday, Maeve O’Reilly, Catriona Gilmour Hamilton, Arzhang Ardahan, Simon E Kolstoe, Katie Gillies
Research Ethics, 12 June 2023
Open Access
Abstract
Research consent processes must provide potential participants with the necessary information to help them decide if they wish to join a study. On the Oxford ‘A’ Research Ethics Committee we’ve found that current research proposals mostly provide adequate detail (even if not in an easily comprehensible format), but often fail to support decision making, a view supported by published evidence. In a previous paper, we described how consent might be structured, and here we develop the concept of an Information and Decision Aid (IDA) that can support decision making and be used to guide the dialogue between researcher and potential participant. Our proposal requires limited changes to current processes or paperwork and would provide an easily accessible document for others that the potential participant might approach for advice. It could later be integrated with the Informed Consent Form to ensure all matters of concern to the individual participant have been addressed before consent is formally signed off.

Parental perceptions of informed consent in neonatal emergency research
Susanne Tippmann, Janine Schäfer, Christine Arnold, Julia Winter, Norbert Paul, Eva Mildenberger, André Kidszun
Z Geburtshilfe Neonatol, 2023; 227(03)
Abstract
Background and Objective
Obtaining informed consent in neonatal emergency research is challenging. The aim of this study was to assess parental perceptions of informed consent following participation in a clinical trial in neonatal emergency care.
Methods
This was a supplementary analysis of a randomised controlled trial comparing video and direct laryngoscopy for neonatal intubation. After obtaining informed consent for the clinical trial, parents were asked to answer a series of self-administered questions about their perceptions of the consent process. Informed consent had been given either before birth, after birth but before inclusion in the trial, or after inclusion in the trial.
Results
Of the 63 preterm and term infants who participated in the study, we received responses from 33 mothers and 27 fathers (n = 60). Fifty-four (91.5%, n = 59) parents agreed that infants should participate in clinical trials. Fifty-one (85%) parents agreed that parents should be asked for their consent to participate in research studies involving their children. A minority of six (10%) parents would prefer not to be asked to consent to their infant participating in the study. Fifty-three (89.8%, n = 59) parents felt that their infant’s participation in this particular trial would be beneficial. Twelve (20%) parents thought that infants who take part in clinical trials generally get better treatment. Almost all parents (56 (93.3%)) felt well informed about the purpose of the trial. Fifty-two (86.7%) parents felt that the informed consent process was satisfactory. One parent (100%, n=1) approached before birth, 23 parents (82.1%, n=28) approached after birth but before enrolment and 26 (83.9%, n=31) parents approached after enrolment were satisfied with the timing of the consent process. Eight (13.3%) parents felt pressured to agree to participate in the study. Of these, two (25%) were approached before enrolment and six (75%) were approached after enrolment. When asked about the best time to discuss consent with parents in clinical trials in neonatal emergency care, 20 (33%) parents said it was before birth, while 40 (67%) parents said it was after birth.
Conclusion
Parents valued their infant’s participation in a clinical trial in neonatal emergency care and considered it important to be asked for consent. Timing seemed to be less important. Deferred consent appears to be a feasible approach to obtaining informed consent for clinical trials in neonatal emergency care. However, future studies need to investigate whether parents feel more pressured to give consent in this way.

Offering Lottery Entry as an Incentive for Research Participation Compromises Informed Consent
Simon Paul Jenkins
Ethics & Human Research, May-June 2023; 45(3) pp 18-28
Abstract
This paper argues that offering entry into a lottery as an incentive to those who participate in research studies represents a challenge to the principle of informed, coercion-free consent that is considered an essential ingredient of permissible recruitment to studies. This is, first, because information about the chances of winning in this context is normally unavailable to potential participants and, without this, they cannot accurately weigh up the risks and potential benefits of participation. Second, even when this information is available, such an incentive capitalizes, I contend, on the difficulty of weighing up small probabilities, exploiting the fact that people tend to be beset by cognitive biases that make it challenging to make decisions rationally. The resulting conclusion is that we should not view lotteries as more ethical than simply paying participants, when the latter is feasible.

Regulatory compliance and readability of informed consent forms in industry-sponsored drug development clinical trials
Research Article
Nahathai Dukaew, Mingkwan Na Takuathung, Wannachai Sakuludomkan, Kanyarat Chairaksa, Preeyaporn Klinjan, Nimit Morakote, Nut Koonrungsesomboon
Clinical Trials, 16 May 2023
Abstract
Background/Aims
An informed consent form is essential in drug development clinical trials. This study aimed to evaluate regulatory compliance and readability of informed consent forms currently being used in industry-sponsored drug development clinical trials.
Methods
This descriptive, cross-sectional study evaluated the informed consent forms of industry-sponsored drug development clinical trials conducted at the Faculty of Medicine, Chiang Mai University, between 2019 and 2020. The informed consent form’s compliance with the three major ethical guidelines and regulations (i.e. International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use E6(R2) Good Clinical Practice; Declaration of Helsinki; and the revised Common Rule) were analyzed. The document length and the readability scores (using Flesch Reading Ease and Flesch-Kincaid Reading Grade) were assessed.
Results
Of 64 reviewed informed consent forms, the average page length was 22.0 ± 7.4 pages. More than half of their length was mainly devoted to three elements: trial procedures (22.9%), risks and discomforts (19.1%), and confidentiality and the limit of confidentiality (10.1%). Although most of the required elements of the informed consent form content were included in most informed consent forms, we identified four elements with often missing information in the form: aspects of research that are experimental (n = 43, 67.2%), involvement of whole-genome sequencing (n = 35, 54.7%), commercial profit sharing (n = 31, 48.4%), and posttrial provisions (n = 28, 43.8%).
Conclusion
The informed consent forms in industry-sponsored drug development clinical trials were long but incomplete. Our findings draw attention to ongoing challenges in industry-sponsored drug development clinical trials, where deficient informed consent form quality continues to exist.

Readability of Consent Forms: Sponsor Templates versus Locally Approved Consent Forms
Dissertation
Joyce D. Brown
Rush University ProQuest Dissertations Publishing, 2023
Abstract
Background
Respect for person is a basic ethical principle of the Belmont Report and includes the need to treat research participants as autonomous individuals during the consenting process. Federal guidance has recommended consents be written at a 6th to 8th grade reading level. However, it is not clear that these reading recommendations actually occur in reality. The overall goal of this project explores whether the results of sponsor provided, and Institutional Review Board (IRB) approved consents at a local site achieve the desired reading levels.
Methods
This quality improvement project identified research studies in the Pulmonary and Critical Care Division of Rush University Medical Center from 2014-2023, where a sponsor consent and a Rush IRB consent were both available. Readability software calculated consent comparison scores. Data resulted from use of the Flesch Reading Ease (FRE), Flesch- Kincaid Grade Level (FKRL), and Simple Measure of Gobbledygook Index (SMOG) scores.
Results
After reviewing the research study records, 18 studies met inclusion criteria for the project and consents selected for the medical intensive care unit recruitment (39%) and (61%) for outpatient pulmonary disorders research. The eighth-grade level for each metric was 60 for FRE, 8 for FKGL and 8 for the Smog Index score. Using a t-test, the mean readability metrics for the sponsor consents was greater than the 8th grade (FRE: 53.75 (SE=1.56), t-test = -3.98; p = < 0.001; FKGL: 9.74 (SE=0.29), t-test = 5.83; p = < 0.000; Smog Index: 12.15 (SE=0.23), t-test = 17.62; p = < 0.000). Similarly, the mean readability metrics for Rush IRB consents was greater X than the 8th grade (FRE: 53.51(SE=0.90), t-test = -7.17; p = < 0.000; FKRL: 9.90 (SE=0.17), ttest =  10.61; p = < 0.000; Smog Index: 12.20 (SE=0.14), t-test = -29.13; p = < 0.000). Paired ttest results conducted on the sponsor and IRB consents show no difference on any of the readability metric and therefore show no statistically significant difference (sponsor vs. Rush IRB for FRE 53.75 vs. 53.51, t-test = -2.32, p = 0.81); for FKGL 9.74 vs 9.90; t-test = 0.83, p = 0.41, and for SMOG 12.15 vs 12.20, t-test = .33, p = 0.73.
Discussion
Readability scored both the sponsor and IRB consent templates above the 8th grade reading level. Additional research is warranted to advance the properties of readability in the sponsor and IRB templates.

A Narrative Review of the Rationale for Conducting Neonatal Emergency Studies with a Waived or Deferred Consent Approach
Review Articles
Anup Katheria, Georg M. Schmölzer, Annie Janvier, Vishal Kapadia, Ola D. Saugstad, Maximo Vento, Alla Kushnir, Mark Tracy, Wade Rich, Ju Lee Oei
Neonatology, 9 May 2023
Abstract
Emergency research studies are high-stakes studies that are usually performed on the sickest patients, where many patients or guardians have no opportunity to provide full informed consent prior to participation. Many emergency studies self-select healthier patients who can be informed ahead of time about the study process. Unfortunately, results from such participants may not be informative for the future care of sicker patients. This inevitably creates waste and perpetuates uninformed care and continued harm to future patients. The waiver or deferred consent process is an alternative model that may be used to enroll sick patients who are unable to give prospective consent to participate in a study. However, this process generates vastly different stakeholder views which have the potential to create irreversible impediments to research and knowledge. In studies involving newborn infants, consent must be sought from a parent or guardian, and this adds another layer of complexity to already fraught situations if the infant is very sick. In this manuscript, we discuss reasons why consent waiver or deferred consent processes are vital for some types of neonatal research, especially those occurring at and around the time of birth. We provide a framework for conducting neonatal emergency research under consent waiver that will ensure the patient’s best interests without compromising ethical, beneficial, and informative knowledge acquisition to improve the future care of sick newborn infants.

Piloting a tool for informed consent comprehension in a cardiovascular clinical trial in South Africa: An IMPI-2 pilot trial substudy (ICC Study)
G C Isiguzo, M A Familusi, K Sliwa, L Thabane, M Ntsekhe, B M Mayosi, J de Vries
South African Medical Journal, 12 April 2023
Abstract
Background
Informed consent is a key requirement in research. However, the comprehension of information presented is rarely evaluated prior to or during the research. Ensuring that participants understand the key issues in trials is important, not just for ethical reasons, but also because it can help set patient expectations. We evaluated the feasibility of using the University of California Brief Assessment of Capacity to Consent (UBACC) questionnaire to guide informed consent comprehension in the pilot study for the second Investigation of the Management of Pericarditis in Africa (IMPI-2) trial. IMPI-2 is a randomised controlled trial (RCT) on the use of alteplase-facilitated pericardial drainage, compared with routine care among patients with large pericardial effusion. We used an abbreviated version of the UBACC to evaluate participant comprehension of key elements of the consent documentation and to guide discussions.
Method
Comprehension was assessed using a 10-item UBACC at baseline, 6 weeks, 3 months and 6 months follow-up to reiterate the information about the trial. Each response was scored from 0 to 3 and the sum at each visit was recorded to represent comprehension. A UBACC score ≥25 was considered adequate comprehension. Bivariate logistic regression was performed to evaluate comprehension over time. A multivariate analysis was conducted to identify predictors of UBACC score.
Results
The Informed Consent Comprehension (ICC) Study included 71 participants with a median age of 42 years; 45% were females and 49% had at least a secondary level of education. Level of comprehension improved with time; the odds of passing the evaluation at baseline compared with 6 months was higher (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.17 – 1.65, p<0.001). Not using interpreters and having a secondary level of education were associated with higher comprehension. Despite knowing that they were participating in research, many participants still did not accept that the trial drug may have no effect.
Conclusion
It is feasible to use the UBACC questionnaire for informed consent comprehension evaluation in RCTs. Repeated learning during follow-up improves comprehension over time, while a low level of education and use of interpreters reduces comprehension.