Ethical Justification for Deferral of Consent in the AcT Trial for Acute Ischemic Stroke

Ethical Justification for Deferral of Consent in the AcT Trial for Acute Ischemic Stroke
Research Article
Hannah Faris, Brian Dewar, Dar Dowlatshahi, Alnar Ramji, Carol Kenney, Stacey Page, Brian Buck, Michael D. Hill, Shelagh B. Coutts, Mohammed Almekhlafi, Tolulope Sajobi, Nishita Singh, Arshia Sehgal, Richard H. Swartz, Bijoy K. Menon, Michel Shamy
Stroke, 23 May 2022
Abstract
The AcT trial (Alteplase Compared to Tenecteplase) compares alteplase or tenecteplase for patients with acute ischemic stroke. All eligible patients are enrolled by deferral of consent. Although the use of deferral of consent in the AcT trial meets the requirements of Canadian policy, we sought to provide a more explicit and rigorous approach to the justification of deferral of consent organized around 3 questions. Ultimately, the approach we outline here could become the foundation for a general justification for deferral of consent.

Should informed consent and information related to patient recruitment in clinical trials be available to the reader of scientific articles? A case study in dentistry

Should informed consent and information related to patient recruitment in clinical trials be available to the reader of scientific articles? A case study in dentistry
Research Article
Clovis Mariano Faggion Jr
Accountability in Research, 16 May 2022
Abstract
Ethical aspects in research should be transparently reported. This study aimed to investigate whether informed consent and information related to patient recruitment in clinical studies are well-reported in the scientific literature. Randomized clinical trials (RCTs) on root coverage procedures published between November 2016 to November 2021 were selected from the PubMed database. Items/questions were used to guide the extraction of data related to patient recruitment, with a focus on the detailed report of informed consent used to clarify the research to the patient. Data were extracted from the published article and the respective research protocol published in a public registry. Information related to potential selective outcome reporting (SOR) was also extracted. 187 documents were initially screened and 74 reports of RCTs were included. No informed consent was published in the article. Only one research protocol provided a link to the informed consent. Deviations from reporting in the research protocol and published article were found, suggesting SOR. Informed consent and information related to patient recruitment in RCTs on root covering procedures are severely underreported. The present findings may stimulate further discussion and debate on the need for making this information publicly available.

Patient and Proxy Recall After Providing Written or Oral Informed Consent to Participate in an Interventional Trial

Patient and Proxy Recall After Providing Written or Oral Informed Consent to Participate in an Interventional Trial
Research Letter Ethics
Angela Huttner, Elodie von Dach, Virginie Prendki, Stephan Harbarth, Laurent Kaiser
JAMA Network Open, 13 May 2022; 5(5)
Abstract
Introduction
Patients’ understanding and recall after granting written consent for trial participation are known to be suboptimal.1 A 2006 study among 44 hospitalized patients providing written consent to an interventional trial found that only 68% remembered the purpose of the trial 10 days later; one-fifth had no recollection of having consented to any study.2 Recall by patients granting oral consent, and by the healthy proxies granting written consent for patients without capacity, is underreported. We compared recall rates after 30 days for participation in a randomized clinical trial (RCT) among patients with capacity who had given written or oral consent and for proxies of patients without capacity who had given written consent.
Methods
The RCT and this nested cohort study were approved by the Geneva Cantonal Ethics Commission. All participants or their proxies provided informed consent. This study is reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. This nested prospective cohort study included all patients with capacity and all proxies of patients without capacity participating at a single site (Geneva University Hospital, Switzerland) of a multicenter RCT by von Dach et al3 comparing antibiotic durations for gram-negative bacteremia in adults hospitalized between 2017 and 2019. In line with Swiss law, consent could be granted in writing by the patient, orally with a witness’s signature (for patients who were illiterate or physically unable to sign), or in writing by the proxy of a patient without capacity. Our primary outcome was the 30-day recall rate for RCT participation among patients providing written or oral consent and proxies providing written consent. On day 30, patients and proxies were contacted for the RCT’s first clinical follow-up. They were asked whether they remembered (1) that they were (or their dependent was) participating in the RCT, (2) that they had granted consent, (3) the RCT’s purpose, and (4) potential risks. Data were analyzed in Stata statistical software version 16.0 (StataCorp). Comparisons were performed with Fisher exact test; associations were 2-sided with P = .05 considered significant. Univariate logistic regression was used to assess factors potentially associated with recall. Data were analyzed from November 1 to 30, 2021.
Results
The Geneva site enrolled 240 patients in the RCT. Consent was granted in writing by 167 patients (69%), orally by 16 patients (7%), and in writing by the proxies of 57 patients (24%) without capacity. At 30 days, data were available for 231 patients (96%): 4 patients (2%) had died, 3 patients (1%) had been otherwise lost to follow-up, and 2 patients (1%) were not asked the nested study’s questions. Median (IQR) patient age was 83 (74-89) years; 157 patients (65%) were women (Table 1). All proxies were next of kin. The time spent presenting the study and whether participants and proxies asked questions are detailed in Table 1. A total of 111 of 161 patients providing written consent (69%), 9 of 14 patients providing oral consent (64%), and 36 of 56 proxies (64%) remembered that they or their loved ones were participating in a trial. Furthermore, 60 patients providing written consent (37%), 5 patients providing oral consent (36%), and 21 proxies (37%) recalled granting consent; 40 patients providing written consent (25%), 5 patients providing oral consent (36%), and 20 proxies (36%) remembered the purpose of the trial. Few remembered the trial’s potential risks (Table 1). In linear and univariate regression models, neither the time spent with patients or proxies, whether they had questions, nor consent modality was associated with improved recall (Table 2).
Discussion
This cohort study among hospitalized patients, most of whom were elderly and all of whom had been acutely ill and hospitalized in the days prior, found that most patients had poor recall of their written consent to participate in an interventional trial (63%), a finding consistent with earlier studies.1,2 Yet recall after oral consent was no worse (64%), suggesting that the act of signing a document was not associated with improved retention or understanding. Perhaps most strikingly, recall by proxies, presumably healthy, providing written consent for their loved ones was as poor as that of patients who were seriously ill (63%). This study is limited by the impossibility of randomizing candidates or proxies to oral or written consent and by the small number of patients granting oral consent. The ability of patients—deemed competent by their physicians—to grant truly informed consent has long been in question.4,5 The ability of their proxies, physically healthy but emotionally stressed, to do the same requires further exploration. While these results require confirmation in larger studies, the act of signing consent, as opposed to granting it orally, was not associated with later recall or understanding.

Informed Consent for Potential Recipients of Pig Kidney Xenotransplantation in the United States

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

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

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

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

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

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

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.