Issues About Digital Informed Consent in Clinical Research
Freade Akbar, Ray Wagiu Basrowi
Indonesian Journal of Community and Occupational Medicine, July 2022; 2(1) pp 40-7
Open Access
Abstract
Introduction
Informed consent is a concrete form of moral and ethical values that urgently needs to be emphasized, especially in research that requires the role of humans as subjects and is commonly associated with experimental research. Informed consent itself consists of two forms of print and digital, along with the times many parties began to examine how the role of informed consent, the advantages and disadvantages between print and digital, the application of good digital informed consent, and how information about research should be conveyed to the research subject so that it is easy to understand and in accordance with moral and ethical standards. The purpose of this article is to address issues related to digital informed consent in clinical research.
Methods
We conducted a search on the SpingerLink database in March 2022 to see various publications in the last 2 years related to electronic informed consent using keywords: digital, informed consent, research.
Results
Total 4 articles as source of literature review. Recent research shows the tendency of research subjects to choose digital informed consent because content is easier to personalize, makes it easier to understand content that is only needed by the subject, and the ease of adding digital content in certain forms of media such as audio, and video into digital formats. From the researcher’s side will increase the active participation and number of study subjects, making it easier for long-term interaction, especially follow-up research. There are 4 types of informed consent based on utilization for research and 5 informed consent processes that must be carried out in clinical research, which is attempted using language that is easily understood by the research subject and dynamic for further research.
Conclusions
Informed consent in any form constitutes the autonomy right of the subject. Digital formats provide better prospects in facilitating communication to research subjects. But this ease must be accompanied by the consistency of the application of the standard informed consent process, even in intervention studies with biological samples this is more stringent. Informed consent given to the subject must use language that is easy to understand, and transparent. The subject of the study is given the right at any time to exit the research. In the future, the issue of morals and ethics of research will grow, and more dynamic informed consent is needed, especially for interventional clinical research.

Keys to improving the informed consent process in research: Highlights of the i-CONSENT project
Editorial
Jaime Fons-Martinez, Cristina Ferrer-Albero, Javier Diez-Domingo
Health Expectations, 27 July 2022
Open Access
Excerpt
    The ethical and legal governance of all aspects of informed consent in research is becoming increasingly extensive and complex. Instead of a single directive, informed consent is governed by a series of international rules applied to biomedical research, clinical trials and biobanks, while various ethical guidelines for research have been published by different international bodies.

Informed consent is an essential part of any research involving humans, but the array of available guidelines can complicate the informed consent process for sponsors, researchers and participants. Sponsors, in particular, find it difficult to adapt the informed consent process to the characteristics of the participants. Moreover, because of the length and complexity of informed consents, some participants may misconstrue key points and agree to participate in a trial that they do not fully understand. In these cases, the decision on their participation is mainly based on discussions with the researcher, which lacks traceability…

Success rate of acquiring informed consent and barriers to participation in a randomized controlled trial of laparoscopic versus open surgery for non-curative stage IV colon cancer in Japan
Journal Article
Tomonori Akagi, Kosuke Suzuki, Yohei Kono, Shigeo Ninomiya, Tomotaka Shibata, Yoshitake Ueda, Hidefumi Shiroshita, Tsuyoshi Etoh, Akio Shiomi, Masaaki Ito, Jun Watanabe, Kohei Murata, Yasumitsu Hirano, Manabu Shimomura, Shunsuke Tsukamoto, Yukihide Kanemitsu, Masafumi Inomata
Japanese Journal of Clinical Oncology, 22 July 2022
Abstract
Background
Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC.
Methods
A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires.
Results
In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n = 84) or open surgery group (n = 84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients’ preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization.
Conclusions
The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

Future informed consent research – a step in the wrong direction!
JM Clements, LJ Convie, SJ Kirk, M Clarke
British Journal of Surgery, 22 July 2022; 109(Suppl 4)
Open Access
Abstract
Introduction
Over 300 million invasive procedures occur globally every year, each requiring patient informed consent. No single outcome measure exists for measurement of the informed consent process. A core outcome set (COS) for informed consent for therapy consisting of 9 outcomes has been developed to define what outcomes matter to key stakeholders in the informed consent process. We aimed to identify the frequency of uptake of the COS consent outcomes in future randomised control trials.
Methods
A systematic review of prospectively registered randomised control trial protocols was performed. The online trial registries World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP) and the US National Library of Medicine ClinicalTrials.gov were searched. All studies assessing interventions designed to improve the informed consent process were considered.
Results
627 registered protocols were identified of which 22 met the inclusion criteria. Only two core outcomes were reported in any prospective interventional consent trial protocols. Patient satisfaction with the consent process and patient satisfaction with the amount of information were observed which employed unvalidated tools. Patient knowledge was the predominant primary outcome measure (n=20). Unvalidated measurement tools were used in all cases. Patient anxiety, decisional regret and decisional conflict were the only outcomes consistently measured using validated measurement tools.
Conclusion
The use of unvalidated outcome measurement tools in future consent trials are widespread. This review has highlighted the clear disconnect between chosen outcomes in future consent trial protocols and an established informed consent COS, limiting the potential value of outputs in future consent trials.
Take-home message
A clear disconnect exists between the outcome measures used in prospective consent randomised trials and an established core outcome set for informed consent for therapy.

When is it impractical to ask informed consent? A systematic review
Review Article
Sara JM Laurijssen, Rieke van der Graaf, Wouter B van Dijk, Ewoud Schuit, Rolf HH Groenwold, Diederick E Grobbee, Martine C de Vries
Clinical Trials, 1 July 2022
Abstract
Background
Informed consent is one of the cornerstones of biomedical research with human subjects. Research ethics committees may allow for a modification or a waiver of consent when the research has social value, involves minimal risk, and if consent is impractical to obtain. While the conditions of social value and minimal risk have received ample attention in research ethics literature, the impractical condition remains unclear. There seem to be different interpretations of the meaning of impractical within academic literature. To address this lack of clarity, we performed a systematic review on the interpretation of impractical.
Methods
First, we examined international research ethics guidelines on their usage and interpretation of impractical. Next, we used international ethical guidelines to identify synonyms of the term “impractical.” Accordingly, PubMed, Embase, and Web of Science were searched for articles that included “informed consent” and “impractical” or one of its synonyms.
Results
We found that there were only a few international ethics guidelines that described what could be considered impractical. Out of 2329 identified academic articles, 42 were included. Impractical was used to describe four different conditions: (1) obtaining informed consent becomes too demanding for researchers, (2) obtaining informed consent leads to invalid study outcomes, (3) obtaining informed consent harms the participant, and (4) obtaining informed consent is meaningless for the participant.
Conclusion
There are conditions that render conventional informed consent truly impractical, such as untraceable participants or harm for participants. At the same time, researchers have a moral responsibility to design an infrastructure in which consent can be obtained, even if they face hardship in obtaining consent. In addition, researchers should seek to minimize harm inflicted upon participants when harm may occur as a result of the consent procedure. Invalidity of research due to consent issues should not be regarded as impractical but as a condition that limits the social value of research. Further research is essential for when a waiver of informed consent based on impractical is also reasonable.

Toward Meeting the Obligation of Respect for Persons in Pragmatic Clinical Trials
Morain SR, Kraft SA, Wilfond BS, Mcguire A, Dickert NW, Garland A, Sugarman J
The Hastings Center Report, 1 May 2022; 52(3) pp 9-17
Abstract
Research ethics oversight systems have traditionally emphasized the informed consent process as the primary means by which to demonstrate respect for prospective subjects. Yet how researchers can best fulfill the ethical obligations of respect for persons in pragmatic clinical trials (PCTs)-particularly those that may alter or waive informed consent-remains unknown. We propose eight dimensions of demonstrating respect in PCTs: (1) engaging patients and communities in research design and execution, (2) promoting transparency and open communication, (3) maximizing agency, (4) minimizing burdens and promoting accessibility, (5) protecting privacy and confidentiality, (6) valuing interpersonal interactions with clinicians and study team members, (7) providing compensation, and (8) maximizing social value. While what respect requires in the context of PCTs will vary based on the nature of the PCT in question, the breadth of these dimensions demonstrates that respect obligations extend beyond informed consent processes.

Improving first-in-human and window-of-opportunity informed consent forms through participant feedback
Anna Avinger, Hannah Claire Sibold, Gavin Paul Campbell, Eli Rowe Abernethy, John Bourgeois, Tekiah McClary, Shannon M. Blee, Margie D. Dixon, R. Donald Harvey, Rebecca D. Pentz
Journal of Clinical Oncology, 1 June 2022 [2022 ASCO Annual Meeting]
Open Access
Abstract
Background
Although patient advocates have created templates for standard consent forms, assessing patient preferences for First in Human (FIH) and Window of Opportunity (WO) trials consents is important given their unique risks. FIH trials are the first time a drug is tested in humans. In WO trials, treatment naïve patients receive a therapeutic agent in the window of time between diagnosis and standard of care (SOC) surgery. Our goal was to determine patient-preferred presentation of important information in FIH and WO consent forms.
Methods
The study consisted of two phases: (1) analysis of consents for FIH and WO oncology trials open at a cancer center between 2019 and 2022; (2) interview patients who had reviewed consents for FIH or WO trials during the consent process. FIH consents were analyzed for the location(s) of information stating that the study drug has not been tested in humans (FIH info). The WO consents were analyzed for the location(s) of information stating the risk that trial may delay SOC surgery (WO info). Participants were asked about their preferred placement of the information in their own trial’s consent form and whether the consent was clear. Interviews were audio-recorded and double coded. Consent form analysis was compared to patients’ preferences.
Results
25 consents [20 FIH; 5 WO] were analyzed. 19/20 FIH consent forms included FIH info, and 4/5 WO consent forms included WO info. 42 patients were approached [19 FIH; 23 WO]; 34 [17 FIH; 17 WO] participated. 12/17 (71%) WO participants thought that the trial explanation in the consent form was clear. Conversely, only 9/17 (53%) FIH participants found it clear.
Conclusions
Patients preferred that the important FIH and WO information be placed early in the consent, though exactly where varied. 82% of FIH participants wanted FIH information in the purpose, while only 19% of WO participants clearly preferred that WO information be in the purpose, and 41% preferred WO information to remain in the risks section. Using consent templates that reflect patient preferences accurately is essential for ethical informed consent; however, a one-size fits all approach may not accurately capture patient preferences, so multiple templates may be necessary.

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
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
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.