Leveraging Blockchain Technology for Informed Consent Process and Patient Engagement in a Clinical Trial Pilot
Baldwin C. Mak, Bryan T. Addeman, Jia Chen, Kim A. Papp, Melinda J. Gooderham, Lyn C. Guenther, Yi Liu, Uli C. Broedl, Marianne E. Logger
Blockchain in Healthcare Today, 14 October 2021; 4
Abstract
Objective
Despite the implementation of quality assurance procedures, current clinical trial management processes are time-consuming, costly, and often susceptible to error. This can result in limited trust, transparency, and process inefficiencies, without true patient empowerment. The objective of this study was to determine whether blockchain technology could enforce trust, transparency, and patient empowerment in the clinical trial data management process, while reducing trial cost.
Design
In this proof of concept pilot, we deployed a Hyperledger Fabric-based blockchain system in an active clinical trial setting to assess the impact of blockchain technology on mean monitoring visit time and cost, non-compliances, and user experience. Using a parallel study design, we compared differences between blockchain technology and standard methodology.
Results
A total of 12 trial participants, seven study coordinators and three clinical research associates across five sites participated in the pilot. Blockchain technology significantly reduces total mean monitoring visit time and cost versus standard trial management (475 to 7 min; P = 0.001; €722 to €10; P = 0.001 per participant/visit, respectively), while enhancing patient trust, transparency, and empowerment in 91, 82 and 63% of the patients, respectively. No difference in non-compliances as a marker of trial quality was detected.
Conclusion
Blockchain technology holds promise to improve patient-centricity and to reduce trial cost compared to conventional clinical trial management. The ability of this technology to improve trial quality warrants further investigation.

Expectations, experiences and preferences of patients and physicians in the informed consent process for clinical trials in oncology
Original Article
Laura Gangeri, Sara Alfieri, Margherita Greco, Marta Scrignaro, Elisabetta Bianchi, Paolo Casali, Davide Ferraris, Claudia Borreani
Supportive Care in Cancer, 7 October 2021
Abstract
Purpose
The aim of the present study was to explore (1) informed consent (IC) representations, level of understanding, needs, and factors that influence the willingness of cancer patients to participate in randomized controlled trials (RCTs) (phase I) and (2) representations, experiences, and critical issues of physicians involved in the same process (phase II).
Methods
Semi-structured interviews were conducted with 20 cancer patients who had been asked to enroll in a phase II/III RCT (phase I). Two focus groups were conducted with 13 physicians enrolled in the same process (phase II). The content produced was analyzed through a thematic analysis.
Results
The themes that emerged in the first phase I were grouped into six categories: IC representation, randomization, experimentation, meeting with the physician, factors that influence the willingness to participate, and trial participants’ needs. The themes emerged in the phase II were grouped into four: IC representation, critical issues of the IC, relationship, and recruitment of trial participants. Each theme is articulated into sub-themes and deeply discussed.
Conclusion
This study highlights (1) the gap between what is ethically demanded in a RCT consultation and the reality of the situation and (2) the difference in perceptions between patients and physicians with reference to the meaning, objectives, and level of understanding of IC.

Deferred Consent in an Acute Stroke Trial from a Patient, Proxy, and Physician Perspective: A Cross-Sectional Survey
Original Work
Inez Koopman, Dagmar Verbaan, W. Peter Vandertop, Rieke van der Graaf, Erwin J. O. Kompanje, René Post, Bert A. Coert, Martine C. Ploem, Wouter M. Sluis, Féline E. V. Scheijmans, Gabriel J. E. Rinkel, Mervyn D. I. Vergouwen
Neurocritical Care, 5 October 2021
Open Access
Abstract
Background
In some acute care trials, immediate informed consent is not possible, but deferred consent is often considered problematic. We investigated the opinions of patients, proxies, and physicians about deferred consent in an acute stroke trial to gain insight into its acceptability and effects.
Methods
Paper-based surveys were sent to patients who were randomly assigned in the Ultra-early Tranexamic Acid After Subarachnoid Hemorrhage (ULTRA) trial between 2015 and 2018 in two tertiary referral centers and to physicians of centers who agreed or declined to participate. The primary outcome measure was the proportion of respondents who agreed with deferral of consent in the ULTRA trial. Secondary outcomes included respondents’ preferred consent procedure for the ULTRA trial, the effect of deferred consent on trust in physicians and scientific research, and the willingness to participate in future research.
Results
Eighty-nine of 135 (66%) patients or proxies and 20 of 30 (67%) physicians completed the survey. Of these, 82 of 89 (92%) patients or proxies and 14 of 20 (70%) physicians agreed with deferral of consent in the ULTRA trial. When asked for their preferred consent procedure for the ULTRA trial, 31 of 89 (35%) patients or proxies indicated deferred consent, 15 of 89 (17%) preferred immediate informed consent, and 32 of 89 (36%) had no preference. None of the patients’ or proxies’ trust in physicians or scientific research had decreased because of the deferred consent procedure. Willingness to participate in future studies remained the same or increased in 84 of 89 (94%) patients or proxies.
Conclusions
A large majority of the surveyed patients and proxies and a somewhat smaller majority of the surveyed physicians agreed with deferred consent in the ULTRA trial. Deferred consent may enable acute care trials in an acceptable manner without decreasing trust in medicine. Future research should investigate factors facilitating the responsible use of deferred consent, such as in-depth interviews, to study the minority of participants who agreed with deferred consent but still preferred immediate informed consent.

Institutional Improvements in Readability of Written Informed Consent Forms Sustained Post-Revised Common Rule
Alison Caballero, Katherine J Leath, Jennifer M Gan
Journal of Clinical and Translational Science, October 2021
Abstract
Obtaining informed consent is a fundamental and ethical practice within human subjects research. Informed consent forms (ICFs) include a large amount of information, much of which may be unfamiliar to research subjects, and the revised Common Rule resulted in several required additions to that language. As limited health literacy impacts many potential subjects, efforts should be made to optimize subjects’ ability to read and understand ICFs. In this brief report, we describe an assessment of ICFs at an academic medical center to evaluate longitudinal changes in readability with the introduction and update of a plain language ICF template.

The Timing of Research Consent
Benjamin Sachs
Ethical Theory and Moral Practice, 28 September 2021
Open Access
Abstract
This essay is about the timing of research consent, a process that involves (potential) participants being given information about, among other things, upcoming research interventions and then being invited to waive their claims against those interventions being undertaken. The standard practice, as regards timing, is as follows: (potential) participants are invited to waive all their claims at a single moment in time, and that point in time immediately follows the information-provision. I argue that there we’re not justified in keeping to this practice. What we ought to do is disaggregate the claim-waiving part of the process and move it later, such that the (potential) participant is invited to waive her claim against the undertaking of any given intervention only the immediate moment before that intervention is to be undertaken.

Strategies to enhance recruitment and consent to intensive care studies: a qualitative study with researchers and patient–public involvement contributors
Original Research
Katie Paddock, Kerry Woolfall, Frith, Megan Watkins, Carrol Gamble, Welters, Bridget Young
BMJ, 22 September 2021; 11(9)
Open Access
Abstract
Objective
Clinical trials and studies in intensive care units (ICUs) have complex consent processes and often encounter problems in recruiting patients. By interviewing research team members about the challenges in critical care research, we aimed to identify strategies to enhance recruitment and consent to ICU studies.
Methods
Semistructured interviews with UK-based researchers (N=17) and patient–public involvement (PPI) contributors (N=8) with experience of ICU studies. Analysis of transcripts of audio-recorded interviews drew on thematic approaches.
Results
Seven themes were identified. Participants emphasised the need for substitute decision-making processes in critical care studies, yet some researchers reported that research ethics committees (RECs) were reluctant to approve such processes. Researchers spoke about the potential benefits of research without prior consent (RWPC) for studies with narrow recruitment windows but believed RECs would not approve them. Participants indicated that the activity of PPI contributors was limited in critical care studies, though researchers who had involved PPI contributors more extensively were clear that their input when designing consent processes was important. Researchers and PPI contributors pointed to resource and staffing limitations as barriers to patient recruitment. Researchers varied in whether and how they used professional consultees as substitute decision-makers, in whether they approached families by telephone to discuss research and in whether they disclosed details of research participation to bereaved relatives.
Conclusion
Critical care research could benefit from RECs having expertise in consent processes that are suited to this setting, better staffing at research sites, more extensive PPI and an evidence base on stakeholder perspectives on critical care research processes. Guidance on professional consultee processes, telephoning relatives to discuss research, RWPC and disclosure of research participation to bereaved relatives could help to harmonise practice in these areas and enhance recruitment and consent to critical care studies.

Reshaping the review of consent so we might improve participant choice
Research Article
Hugh Davies
Research Ethics, 15 September 2021
Open Access
Abstract
Consent is one necessary foundation for ethical research and it’s one of the research ethics committee’s major roles to ensure that the consent process meets acceptable standards. Although on Oxford ‘A’ REC (an NHS Research Ethics Committee based in the UK) we’ve been impressed by the thought and work put into this aspect of research ethics, we’ve continued to have concerns about the suitability and effectiveness of consent processes in supporting decision making, particularly for clinical trials. There’s poor understanding of what people want to help them decide; current processes don’t provide the best grounding for informed consent and there’s inadequate public involvement. We’ve also found a lack of proportionality with researchers failing to adapt consent procedures in proportion to the burdens and consequences of the study. As a result, people are often not best helped to make an informed choice when asked to join a research study. To address these concerns, we considered how we might improve this aspect of research ethics review. Recognising the central importance of the dialogue between the volunteer and researcher, we’ve drawn up a model or flowchart of what we deem good consent practice, proposing consent should be built around four simple steps:

Step 1: Introducing the study and the choices: helping the potential participants get an overview of the proposal and introducing the key issues.

Step 2: Explaining all the details of the study using the detailed Participant Information Sheet.

Step 3: After a gap, if necessary, reviewing and checking understanding.

Step 4: Reaching agreement and recording consent.

These steps, we believe, could help all involved and this article lays out ways we might improve participant choice while complying with accepted principles and current regulations.

Analysing and optimising Informed Consent in cooperation with ethics committees and medical researchers
Igor Matic, Gianni De Nardi, Felix Steiner
AILA Review, 9 September 2021; 34(1) pp 37–56
Open Access
Abstract
Medical researchers are ethically and legally required to inform participants and get written permission before enrolling them into a human research project (Informed Consent). Accordingly, information and consent represent a complex procedure, and the participant concerned “must receive comprehensible oral and written information” (Swiss legislation: Human Research Act (HRA) Art. 16). A triangle of stakeholders is involved in the procedure: ethics committees that review and approve research projects and Informed Consent (IC) documents, medical researchers who produce the documents and discuss enrolment with patients, and patients who have to be informed comprehensibly. From a linguistic point of view, the question arises as to which perceptions of comprehensibility form the basis of the IC process and how shared language can be established considering the complex relationship between these stakeholders. This contribution presents findings from two perspectives (ethics committees and researchers) while considering the needs of all three stakeholders. Firstly, the conceptualisation of comprehensibility among three ethic committees is presented, and steps toward harmonisation are outlined. Secondly, limitations of how researchers conduct oral IC information are analysed, and the measures that were implemented to improve patient information are discussed. A transdisciplinary approach is key in establishing these solutions because they do not stem from linguistic analysis alone but have been developed in close collaboration with members of ethics committees and medical researchers. Thus, the project shows how the expertise of applied linguistics in cooperation with practitioners can deliver an important impact in both academic analysis and optimisation of professional procedures.

Quantifying Withdrawal of Consent, Loss to Follow-Up, Early Drug Discontinuation, and Censoring in Oncology Trials
Brooke E. Wilson, Michelle B. Nadler, Alexandra Desnoyers, Eitan Amir
Journal of the National Comprehensive Cancer Network, 3 September 2021
Open Access
Abstract
Background
Censoring due to early drug discontinuation (EDD) or withdrawal of consent or loss to follow-up (WCLFU) can result in postrandomization bias. In oncology, censoring rules vary with no defined standards. In this study, we sought to describe the planned handling and transparency of censoring data in oncology trials supporting FDA approval and to compare EDD and WCLFU in experimental and control arms.
Methods
We searched FDA archives to identify solid tumor drug approvals and their associated trials between 2015 and 2019, and extracted the planned handling and reporting of censored data. We compared the proportion of WCLFU and EDD between the experimental and control arms by using generalized estimating equations, and performed logistic regression to identify trial characteristics associated with WCLFU occurring more frequently in the control group.
Results
Censoring rules were defined adequately in 48 (59%) of 81 included studies. Only 14 (17%) reported proportions of censored participants clearly. The proportion of WCLFU was higher in the control group than in the experimental group (mean, 3.9% vs 2.5%; β-coefficient, −2.2; 95% CI, −3.1 to −1.3; P<.001). EDD was numerically higher in the experimental arm in 61% of studies, but there was no statistically significant difference in the proportion of EDD between the experimental and control groups (mean, 21.6% vs 19.9%, respectively; β-coefficient, 0.27; 95% CI, −0.32 to 0.87; P=.37). The proportion of EDD due to adverse effects (AEs) was higher in the experimental group (mean, 13.2% vs 8.5%; β-coefficient, 1.5; 95% CI, 0.57–2.45; P=.002). WCLFU was higher in the control group in studies with an active control group (odds ratio [OR], 10.1; P<.001) and in open label studies (OR, 3.00; P=.08).
Conclusions
There are significant differences in WCLFU and EDD for AEs between the experimental and control arms in oncology trials. This may introduce postrandomization bias. Trials should improve the reporting and handling of censored data so that clinicians and patients are fully informed regarding the expected benefits of a treatment.

Exemption from informed consent: When it is possible in investigational product and drug trials?
Review Article
Swati Verma
Saudi Journal of Anesthesia, 2 September 2021; 15(4) pp 428-430
Abstract
One of the most important ethical step in conducting investigational product trials or drug trials is obtaining informed consent from the participants. Although consent from the participants regarding participation is of prime importance but is not always practical or feasible. There may be several instances where it is practically impossible to obtain informed consent, whereas in some cases, obtaining informed consent from the trial participants adversely affects the quality and validity of the study data. Obtaining informed consent is a highly complex and technical process if the participants are not literate or suffering from a terminal illness, Also in some instances obtaining informed consent regarding the washout of prior prescribed medicine which may affect the trial outcomes. Although many guidelines exist for obtaining proper informed consent while very scarce literature exists on the instances where it can be waived off. Therefore, this brief narrative review aims to provide insight into currently available knowledge about when to obtain informed consent during testing of investigational product trials and drug trials and other possible scenarios where it can be waived off considering the effects of the washout period.