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.

Design and validation of two instruments to analyze and evaluate the formal quality in the informed consent process of clinical trials with medicinal products
Original
Andrea G. Jaramillo Vélez, Margarita Aguas Compaired, Montserrat Granados Plaza, Eduardo L. Mariño, Pilar Modamio
Farmacia Hospitalaria, 16 March 2023
Abstract
Objective
The activity of sponsors and Ethics Committees for Research with medicines has increased in recent years. The objective was to design and validate 2 instruments to analyze and evaluate the formal quality of the patient information sheet and the informed consent form of clinical trials with drugs, in accordance with the legislation.
Methods
Design (Guideline for good clinical practice and European and Spanish regulations); validation (Delphi method and expert consensus: concordance ≥ 80%); reliability (inter-observer method, Kappa index). 40 patient information sheets/informed consent forms were evaluated.
Results
Very good concordance was obtained in both checklists (k ≥ 0.81, p b 0.001). The final versions consisted of checklist-patient information sheet: 5 sections, 16 items and 46 sub-items; and checklist-informed consent form: 11 items.
Conclusion
The instruments developed are valid, reliable and facilitate the analysis, evaluation, and decision-making on the patient information sheets/informed consent forms of clinical trials with drugs.

Editor’s note: This is a Spanish language publication. Farmacia Hospitalaria is a publication of the Spanish Hospital Pharmacy Society.

Patients acceptance and comprehension to written and verbal consent (PAC–VC)
Robert C. Welsh, Shane Kimber, Justin Ezekowitz, Rabia Kashur
BMC Medical Ethics, 23 February 2023; 24(14)
Open Access
Abstract
Background
Acute myocardial infarction (AMI) research is challenging as it requires enrollment of acutely ill patients. Patients are generally in a suboptimal state for providing informed consent. Patients’ understanding to verbal assents have not been previously examined in AMI research. Patients’ Acceptance and Comprehension to Written and Verbal Consent (PAC–VC) compared patients’ understanding and attitudes to verbal and written consents in AMI RCTs.
Methods
PAC–VC recruited patients from 3 AMI trials using both verbal N = 12 and written N = 6 consents. We compared patients’ understanding using two survey questionnaires. The first questionnaire used open-ended questions with multiple choice answers. The second questionnaire used a 5-point Likert scale to measure patients understanding and attitudes to the consent process. Overall answers average scores were categorized into three groups: Adequate understanding (71–100) %, Partial understanding (41–70)% and Inadequate understanding (0–40)%.
Results
Responses showed patients with verbal assent had adequate understanding to most components of informed consent, close to those of written consent. Most patients did not read written information entirely and believed that it is not important to make a final decision. Patients favoured to have written information be part of the consent but not necessarily presented during the initial consent process. Patients felt less pressured in the verbal assent arm than those of written consent.
Conclusion
Patients had adequate understanding to most components of verbal assent and comparable to those of written consent. Utilizing verbal assents in the acute care setting should be further assessed in larger trials.

Electronic informed consent: effects on enrolment, practical and economic benefits, challenges, and drawbacks—a systematic review of studies within randomized controlled trials
Review
Ana Teresita Mazzochi, Martin Dennis, Ho-Yan Yvonne Chun
Trials, 21 February 2023; 24(127)
Open Access
Abstract
Background
Enrolment is one of the most challenging aspects of conducting clinical trials, preceded by the process of informed consent (IC). Different strategies to improve recruitment in clinical trials have been used, including electronic IC. During COVID-19 pandemic, barriers to enrolment have been evident. Although digital technologies were acknowledged as the future of clinical research and potential advantages were shown for recruitment, electronic informed consent (e-IC) has not yet been globally adopted. The purpose of this review is to investigate the effect of using e-IC on enrolment, practical and economic benefits, challenges, and drawbacks when compared to traditional informed consent, through a systematic review.
Methods
Embase, Global Health Library, Medline, and The Cochrane Library databases were searched. No limit was set for publication date, age, sex, or study design. We included all studies within a randomized controlled trial (RCT), published in English, Chinese or Spanish, evaluating the electronic consent process used in the parent RCT. Studies were included if any of the three components ((i) information provision, (ii) participant’s comprehension, (iii) signature) of the IC process was designed as electronic, whether administered remotely or face-to-face. The primary outcome was the rate of enrolment to the parent trial. Secondary outcomes were summarized according to the various findings reported on the use of electronic consent.
Results
From a total of 9069 titles, 12 studies were included in the final analysis with a total of 8864 participants. Five studies of high heterogeneity and risk of bias showed mixed results on the efficacy of e-IC on enrolment. Data of included studies suggested e-IC could improve comprehension and recall of study-related information. Meta-analysis could not be conducted due to different study designs and outcome measures and the predominantly qualitative findings.
Conclusion
Few published studies have investigated the impact of e-IC on enrolment and findings were mixed. e-IC may improve participant’s comprehension and recall of information. High-quality studies are needed to evaluate the potential benefit of e-IC to increase clinical trial enrolment.

Improving oncology first-in-human and window of opportunity informed consent forms through participant feedback
Research
Anna M. Avinger, Hannah Claire Sibold, Gavin Campbell, Eli Abernethy, John Bourgeois, Tekiah McClary, Shannon Blee, Margie Dixon, R. Donald Harvey, Rebecca D. Pentz
BMC Medical Ethics, 19 February 2023; 24(12)
Open Access
Abstract
Background
Although patient advocates have developed templates for standard consent forms, evaluating patient preferences for first in human (FIH) and window of opportunity (Window) trial consent forms is critical due to their unique risks. FIH trials are the initial use of a novel compound in study participants. In contrast, Window trials give an investigational agent over a fixed duration to treatment naïve patients in the time between diagnosis and standard of care (SOC) surgery. Our goal was to determine the patient-preferred presentation of important information in consent forms for these trials.
Methods
The study consisted of two phases: (1) analyses of oncology FIH and Window consents; (2) interviews of trial participants. FIH consent forms were analyzed for the location(s) of information stating that the study drug has not been tested in humans (FIH information); Window consents were analyzed for the location(s) of information stating the trial may delay SOC surgery (delay information). Participants were asked about their preferred placement of the information in their own trial’s consent form. The location of information in the consent forms was compared to the participants’ suggestions for placement.
Results
34 [17 FIH; 17 Window] of 42(81%) cancer patients approached participated. 25 consents [20 FIH; 5 Window] were analyzed. 19/20 FIH consent forms included FIH information, and 4/5 Window consent forms included delay information. 19/20(95%) FIH consent forms contained FIH information in the risks section 12/17(71%) patients preferred the same. Fourteen (82%) patients wanted FIH information in the purpose, but only 5(25%) consents mentioned it there. 9/17(53%) Window patients preferred delay information to be located early in the consent, before the “Risks” section.  3/5(60%) consents did this.

When research becomes practice: the concept of the therapeutic misconception and challenges to consent in clinical trials
Sarah Heynemann, Wendy Lipworth, Sue-Anne McLachlan, Jennifer Philip, Tom John, Ian Kerridge
Internal Medicine Journal, 13 December 2022
Open Access
Abstract
Many factors influence patients’ decisions to participate in clinical trials. For many, the primary motivation is the possibility that they might derive some benefit from participation. This is particularly true for patients with limited treatment options, such as patients with advanced cancer. While this is not surprising, it is potentially problematic if patients fail to recognise the distinction between research and clinical care (a phenomenon known as the ‘therapeutic misconception’). This is becoming increasingly problematic as clinical trial designs become more complex, as clinical trials become more embedded in routine clinical care, and as trials are increasingly used by patients and clinicians to access new diagnostic platforms and therapies. We outline some of these recent trends, focusing on the cancer clinical trials landscape as this provides a good case study of the phenomenon. We conclude by making preliminary suggestions that changes to the consent process, perhaps using ‘dynamic consent’ platforms, might help to mitigate the therapeutic misconception and note the need for further research to guide strategies for improving communication and decision-making.

Incentivization and the moral problem of involuntary consent in medical research
Review
Victor Chidi Wolemonwu
History and Philosophy of Medicine, 18 January 2023
Open Access
Abstract
The legal and moral permissibility of clinical research entails that researchers must secure the voluntary, informed consent of prospective research participants before enrolling them in studies. In seeking the consent of potential participants, researchers are also allowed to incentivise the recruitment process because many studies would fail to meet enrollment goals without a financial incentive for participation. Some philosophers and bioethicists contend that the use of incentives to secure consent from research subjects is problematic because it constitutes undue inducement and a coercive offer. Some proponents of this view are Ruth Macklin (1981, 1989) and Joan McGregor (2005). Macklin claims that it is ethically inappropriate to pay research subjects. The payment is likely to coerce the research subject, thereby violating the ethical requirement on the voluntariness of research participation. Also, such offers can prompt subjects to lie, deceive or conceal information that, if known, would disqualify them as participants. For McGregor, incentives could be undue and coercive because they make offerees better off relative to their baseline as well as constrain them to accept the offer of incentives as the only eligible choice or option. I argue that coercive offers are distinct from undue inducement. Coercive offers are essentially morally objectionable because by making people accept an offer through threats for the sake of some interests or ends, the offeror vitiates the offeree’s capacity to make informed, voluntary, and rational decisions and choices. I further claim that the quantity of an incentive does not render an inducement undue. I contend that the only condition under which incentives are regarded as an undue inducement and as such vitiates an agent’s voluntary consent is if they are offered through deceptive or manipulative means.

Using the consolidated framework for implementation research to guide a pilot of implementing an institution level patient informed consent process for clinical research at an outpatient setting
Research
Xuling Lin, Joanne Yong Ern Yuen, Wei Quan Jeremy Chan, Tushar Gosavi Divakar, Nicole Chwee Har Keong, Lester Chee How Lee, Sumeet Kumar, Chew Seah Tan, Kim Chin Pauline Soon, Yee Pheng Amy Chew, Heriati Mohd Yazid, Farah Julieanna Mohd Saleh, Fenglong Cai, Fui Chih Chai, Nur Fakhirah Mohamed Azwan, Nurhidayah Mohamad Faizal, Siew Choo Lou, Siew Sin Priscilla Tan, Cut Marini Jarimin, Gowri Michael Stanley, Khadijah Hussien, Nurhazah Sanmwan, Nur Hidayah Amran, Nurliana Ramli, Shermyn Xiu Min Neo, Louis Chew Seng Tan, Eng King Tan, Elaine Lum
Pilot and Feasibility Studies, 12 January 2023; 9(6)
Open Access
Abstract
Background
In Singapore, research teams seek informed patient consent on an ad hoc basis for specific clinical studies and there is typically a role separation between operational and research staff. With the enactment of the Human Biomedical Research Act, there is increased emphasis on compliance with consent-taking processes and research documentation. To optimize resource use and facilitate long-term research sustainability at our institution, this study aimed to design and pilot an institution level informed consent workflow (the “intervention”) that is integrated with clinic operations.
Methods
We used the Consolidated Framework for Implementation Research (CFIR) as the underpinning theoretical framework and conducted the study in three stages: Stage 1, CFIR constructs were used to systematically identify barriers and facilitators of intervention implementation, and a simple time-and-motion study of the patient journey was used to inform the design of the intervention; Stage 2, implementation strategies were selected and mapped to the Expert Recommendations for Implementing Change (ERIC) taxonomy; Stage 3, we piloted and adapted the implementation process at two outpatient clinics and evaluated implementation effectiveness through patient participation rates.
Results
We identified 15 relevant CFIR constructs. Implementation strategies selected to address these constructs were targeted at three groups of stakeholders: institution leadership (develop relationships, involve executive boards, identify and prepare champions), clinic management team (develop relationships, identify and prepare champions, obtain support and commitment, educate stakeholders), and clinic operations staff (develop relationships, assess readiness, conduct training, cyclical tests of change, model and simulate change, capture and share local knowledge, obtain and use feedback). Time-and-motion study in clinics identified the pre-consultation timepoint as the most appropriate for the intervention. The implementation process was adapted according to clinic operations staff and service needs. At the conclusion of the pilot, 78.3% of eligible patients provided institution level informed consent via the integrated workflow implemented.
Conclusions
Our findings support the feasibility of implementing an institution level informed consent workflow that integrates with service operations at the outpatient setting to optimize healthcare resources for research. The CFIR provided a useful framework to identify barriers and facilitators in the design of the intervention and its implementation process.

Is the informed consent form only a symbolic document in clinical trials?
Mini Review
Buket Gungor
Archives of Pharmacy and Pharmaceutical Sciences, 19 December 2022
Open Access
Excerpt
Being one of the basic principles of clinical research, informed consent is definitely a legal responsibility and ethical duty for health professionals. The purpose of obtaining informed consent is to enable the subjects to make an autonomous decision by providing them with accurate and clear information about the research at the stage of participation. Due to medical advancements and the increasing complexity of diagnostic and experimental methods in clinical research, the prepared Informed Consent Forms (ICFs) have become difficult to understand. Viewing ICFs as just a necessary legal and symbolic document of participation in research often results in an insufficiently informed consent process for subjects. Research shows that the rate of understanding the basic information in the consent forms prepared for the subjects participating in the clinical trials ranged from 52.1% to 75.8%…