Informed Consent: A Monthly Review

June 2022

This digest aggregates and distills key content addressing informed consent from a broad spectrum of peer-reviewed journals and grey literature, and from various practice domains and organization types including international agencies, INGOs, governments, academic and research institutions, consortiums and collaborations, foundations, and commercial organizations. We acknowledge that this scope yields an indicative and not an exhaustive digest product.

Informed Consent: A Monthly Review is a service of the Center for Informed Consent Integrity, a program of the GE2P2 Global Foundation. The Foundation is solely responsible for its content. Comments and suggestions should be directed to:

Paige Fitzsimmons, MA
Associate Director, Center for Informed Consent Integrity
GE2P2 Global Foundation
PDF Version: GE2P2 Global_Informed Consent – A Monthly Review_June 2022

Emergency use of unproven clinical interventions outside clinical trials: ethical considerations

Emergency use of unproven clinical interventions outside clinical trials: ethical considerations
Technical Document
World Health Organisation, 12 April 2022
Open Access
Outbreaks and other events that may become public health emergencies frequently face a lack of  safe and effective therapeutic or preventive interventions, such as drugs specific to the pathogen or condition. WHO and its partners therefore established the “WHO R&D blueprint” in 2016 to stimulate research into diseases or conditions that pose the greatest public health risks because of their epidemic potential or for which there are no or insufficient countermeasures (31). In response to the ethical duty to conduct research during public health emergencies (17), rapid, rigorous, simple clinical trials or other types of research (32, 33) are essential to establish the safety and efficacy of unproven interventions – including “off label” interventions (9) – and to discard those that are unsafe or ineffective to avoid their use in health systems. When a PHEIC is declared, “it is critical that the global research effort is rapid, robust, conducted at scale and coordinated across multiple countries” (33)…

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Patient consent preferences on sharing personal health information during the COVID-19 pandemic: “the more informed we are, the more likely we are to help”

Patient consent preferences on sharing personal health information during the COVID-19 pandemic: “the more informed we are, the more likely we are to help”
Sarah Tosoni, Indu Voruganti, Katherine Lajkosz, Shahbano Mustafa, Anne Phillips, S. Joseph Kim, Rebecca K. S. Wong, Donald Willison, Carl Virtanen, Ann Heesters, Fei-Fei Liu
BMC Medical Ethics, 20 May 2022; 23(53)
Open Access
Rapid ethical access to personal health information (PHI) to support research is extremely important during pandemics, yet little is known regarding patient preferences for consent during such crises. This follow-up study sought to ascertain whether there were differences in consent preferences between pre-pandemic times compared to during Wave 1 of the COVID-19 global pandemic, and to better understand the reasons behind these preferences.
A total of 183 patients in the pandemic cohort completed the survey via email, and responses were compared to the distinct pre-pandemic cohort (n = 222); all were patients of a large Canadian cancer center. The survey covered (a) broad versus study-specific consent; (b) opt-in versus opt-out contact approach; (c) levels of comfort sharing with different recipients; (d) perceptions of commercialization; and (e) options to track use of information and be notified of results. Four focus groups (n = 12) were subsequently conducted to elucidate reasons motivating dominant preferences.
Patients in the pandemic cohort were significantly more comfortable with sharing all information and biological samples (90% vs. 79%, p = 0.009), sharing information with the health care institution (97% vs. 83%, p < 0.001), sharing information with researchers at other hospitals (85% vs. 70%, p < 0.001), sharing PHI provincially (69% vs. 53%, p < 0.002), nationally (65% vs. 53%, p = 0.022) and internationally (48% vs. 39%, p = 0.024) compared to the pre-pandemic cohort. Discomfort with sharing information with commercial companies remained unchanged between the two cohorts (50% vs. 51% uncomfortable, p = 0.58). Significantly more pandemic cohort patients expressed a wish to track use of PHI (75% vs. 61%, p = 0.007), and to be notified of results (83% vs. 70%, p = 0.012). Thematic analysis uncovered that transparency was strongly desired on outside PHI use, particularly when commercialization was involved.
In pandemic times, patients were more comfortable sharing information with all parties, except with commercial entities, where levels of discomfort (~ 50%) remained unchanged. Focus groups identified that the ability to track and receive results of studies using one’s PHI is an important way to reduce discomfort and increase trust. These findings meaningfully inform wider discussions on the use of personal health information for research during global crises.

Equipoise, standard of care and consent: responding to the authorisation of new COVID-19 treatments in randomised controlled trials

Equipoise, standard of care and consent: responding to the authorisation of new COVID-19 treatments in randomised controlled trials
Current controversy
Soren Holm, Jonathan Lewis, Rafael Dal-Ré
Journal of Medical Ethics, 13 May 2022
Open Access
In response to the COVID-19 pandemic, large-scale research and pharmaceutical regulatory processes have proceeded at a dramatically increased pace with new and effective, evidence-based COVID-19 interventions rapidly making their way into the clinic. However, the swift generation of high-quality evidence and the efficient processing of regulatory authorisation have given rise to more specific and complex versions of well known research ethics issues. In this paper, we identify three such issues by focusing on the authorization of molnupiravir, a novel antiviral medicine aimed at reducing the ability of SARS-CoV-2 to multiply in the body, for clinical use by the National Health Service in England and the concomitant testing of molnupiravir through the large-scale Platform Adaptive trial of Novel antivirals for early treatment of COVID-19 In the Community randomized control trial. By analysing the ways in which the authorisation and clinical use of molnupiravir complicate standard approaches to clinical equipoise, standard of care and participant consent in the PANORAMIC randomised control trial, we will explain some ethical implications for clinical trials that aim to study the efficacy and safety of new COVID-19 and other therapeutics when conditional authorisation has already been granted and when such treatments have already been made available to patients by national health providers.

E-Consent – an innovative solution to maintain recruitment momentum in clinical trials during the COVID-19 pandemic

E-Consent – an innovative solution to maintain recruitment momentum in clinical trials during the COVID-19 pandemic
R Almeida-Magana, J. Grierson, H. Maroof, R. Clow, E. Dineen, T. Al-Hammouri, N. Muirhead, C. Brew-Graves, J. Kelly, G. Shaw
European Urology, 2022
Introduction & Objectives
The NeuroSAFE PROOF trial is an ongoing randomized clinical trial evaluating the role of frozen section analysis during robot assisted radical prostatectomy for localized prostate cancer. In response to the COVID-19 crisis, recruitment was halted, and a remote e-Consent solution was designed. The aim of this is to describe the implementation, impact on recruitment rate and patient’s experience using e-Consent.
Materials & Methods
To replace in person consent. An email-based PDF Auto-Archiver feature was created within the Research Electronic Data Capture (REDCap®) environment, following the structure and content of the already approved paper consent. Each question was included as a binary (yes/no) field. An electronic signature field allows the participant to sign the document using a mouse, stylus, or their finger. The signature is captured and appended as a PNG image with a timestamp. This allows research staff to review and electronically co-sign and lock the document. This new tool was approved by the Health Research Authority, Research Ethics Committee, Trial Management Group and Sponsor. Owing to the process collecting patient identifiable data, the platform resides within the REDCap service being hosted behind a Data Safe Haven, which conforms to National Health Service Data Security & Protection Toolkit, General Data Protection Regulation and ISO 27001 Information Security standards.
Before recruitment suspension, the trial was recruiting an average of 9 patients per month, with an increasing trend. (Figure 1) After e- Consent implementation in June 2020, 63 new patients (4/month) have been enrolled despite a second lockdown, none of whom would have been recruited using the old methods given restrictions on face-to-face consultations. Patients have given positive feedback on the use of the platform. The use of this pathway eliminates the need to travel and, therefore, the resultant cost and potential risk of infection, while allowing patients to read and understand information in their own time before providing consent. (Figure Presented)
Guidelines for e-Consent implementation are currently lacking. We present the first description of its use for prostate cancer research. This innovation was critical to resume recruitment for the NeuroSAFE PROOF trial and will be essential for planning future research.

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
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
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)
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.
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.
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).
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.

Emergency department patients’ attitudes towards the use of data in their clinical record for research without their consent

Emergency department patients’ attitudes towards the use of data in their clinical record for research without their consent
Brief Report
Chase Schultz-Swarthfigure, Anne-Maree Kelly, Deborah Zion
Journal of Medical Ethics, 18 May 2022
Health research often uses health information, a subcategory of personal information, collected during clinical encounters. Conditions under which such health information can be used for the secondary purpose of research are set out in state, national and international law. In Australia, consent is required or the relevant conditions for a waiver of consent must be met and approved by a human research ethics committee (HREC). Consent for use of health information for research is rarely sought at an emergency department (ED) presentation. Research often occurs after the index visit and gaining consent can be difficult. Waiver of consent provisions are frequently used, but acceptability of this approach to patients is unclear.
To identify ED patients’ knowledge and attitudes towards the use of health information for research, consent preferences and acceptability of waiver of consent.
An online, anonymous survey of adult patients attending two large EDs in Melbourne, Australia.
103 patients completed the survey. We found that 52% were unaware that health information might be used for research. A majority (77%) felt that HREC approval for use of health information without consent was acceptable. However, 36% would prefer to be contacted regarding consent.
These findings suggest a lack of awareness that health information can be used for research and that waiver of consent is acceptable, but not necessarily preferred, in most of the ED patient population. Efforts to increase awareness and provide opportunities to express preferences about health information use for research are needed.

Patient-centered cross-enterprise document sharing and dynamic consent framework using consortium blockchain and ciphertext-policy attribute-based encryption

Patient-centered cross-enterprise document sharing and dynamic consent framework using consortium blockchain and ciphertext-policy attribute-based encryption
Research Article
Liang Zhang, Haibin Kan, Honglan Huang
Proceedings of the 19th ACM International Conference on Computing Frontiers, 17 May 2022; pp 58–66
Patient-centered healthcare data sharing and data usage consent are gaining popularity. Cross-enterprise document sharing (XDS) is the crucial system of sharing personalized healthcare data. Furthermore, dynamic consent is vital to the XDS system, because it respects people’s autonomy and achieves recognition of data sovereignty. Because of its transparency, blockchain is a powerful system for managing storage and computing without a trusted third party. Besides, ciphertext-policy attribute-based encryption (CP-ABE) extends public-key encryption by implying access control policies in ciphertexts, making it suitable for protecting the privacy of individual healthcare data in versatile cases. Particularly, we use hospital name, “date” and “department” as attribute strings in the access control policies. Consequently, based on consortium blockchain and CP-ABE, we propose a patient-centered XDS and a dynamic consent framework. Compared with previous related literature, we make the proposed framework consistent with current practices and achieve favorable criteria, such as data confidentiality, data recoverability and time-aware ciphertext. Further, we conduct comprehensive experiments to show the feasibility and practicality.