Implementing two-stage consent pathway in neonatal trials
Eleanor Mitchell, Sam J Oddie, Jon Dorling, Chris Gale, Mark John Johnson, William McGuire, Shalini Ojha
Archives of Disease in Childhood – Fetal and Neonatal Edition, 23 December 2021
Perinatal trials sometimes require rapid recruitment processes to facilitate inclusion of participants when interventions are time-critical. A two-stage consent pathway has been used in some trials and is supported by national guidance. This pathway includes seeking oral assent for participation during the time-critical period followed by informed written consent later. This approach is being used in the fluids exclusively enteral from day one (FEED1) trial where participants need to be randomised within 3 hours of birth. There is some apprehension about approaching parents for participation via the oral assent pathway. The main reasons for this are consistent with previous research: lack of a written record, lack of standardised information and unfamiliarity with the process. Here, we describe how the pathway has been implemented in the FEED1 trial and the steps the trial team have taken to support sites. We provide recommendations for future trials to consider if they are considering implementing a similar pathway…
Informed consent and assent guide for paediatric clinical trials in Europe
Pirkko Lepola, Maxine Kindred, Viviana Giannuzzi, Heidi Glosli, Martine Dehlinger-Kremer, Harris Dalrymple, David Neubauer, Geraldine B Boylan, Jean Conway, Jo Dewhurst, Diane Hoffman
Archives of Disease in Childhood, 1 December 2021
Clinical trial sponsors spend considerable resources preparing informed consent (IC) and assent documentation for multinational paediatric clinical trial applications in Europe due to the limited and dispersed patient populations, the variation of national legal and ethical requirements, and the lack of detailed guidance. The aim of this study was to design new easy-to-use guide publicly available on European Medicines Agency’s, Enpr-EMA website for all stakeholders.
Current EU legal, ethical and regulatory guidance for paediatric clinical trials were collated, analysed and divided into 30 subject elements in two tables. The European Network of Young Person’s Advisory Group reviewed the data and provided specific comments. A three-level recommendation using ‘traffic light’ symbols was designed for four age groups of children, according to relevance and the requirements.
A single guide document includes two tables: (1) general information and (2) trial-specific information. In the age group of 6–9 years old, 92% of the trial-specific subject elements can be or should be included in the IC discussion. Even in the youngest possible age group (2–5 years old children), the number of elements considered was, on average, 52%.
The EU Clinical Trial Regulation (2014) does not contain specific requirements exclusively for paediatric clinical trials. This work is the first to extensively collate all the current legal, regulatory and ethical documentation on the IC process, together with input from adolescents. This guide may increase the ethical standards in paediatric clinical trials.
Consent models in Canadian critical care randomized controlled trials: a scoping review
Katie O’Hearn, Jess Gibson, Karla Krewulak, Rebecca Porteous, Victoria Saigle, Margaret Sampson, Anne Tsampalieros, Nick Barrowman, Saoirse Cameron, the Canadian Critical Care Trials Group
Canadian Journal of Anesthesia, 8 November 2021
Our primary objective was to describe consent models used in Canadian-led adult and pediatric intensive care unit (ICU/PICU) randomized controlled trials (RCTs). Our secondary objectives were to determine the consent rate of ICU/PICU RCTs that did and did not use an alternate consent model to describe consent procedures.
Using scoping review methodology, we searched MEDLINE, Embase, and CENTRAL databases (from 1998 to June 2019) for trials published in English or French. We included Canadian-led RCTs that reported on the effects of an intervention on ICU/PICU patients or their families. Two independent reviewers assessed eligibility, abstracted data, and achieved consensus.
We identified 48 RCTs of 17,558 patients. Included RCTs had ethics approval to use prior informed consent (43/48; 90%), deferred consent (13/48; 27%), waived consent (5/48; 10%), and verbal consent (1/48; 2%) models. Fifteen RCTs (15/48; 31%) had ethics approval to use more than one consent model. Twice as many trials used alternate consent between 2010 and 2019 (13/19) than between 2000 and 2009 (6/19). The consent rate for RCTs using only prior informed consent ranged from 54 to 91% (ICU) and 43 to 94% (PICU) and from 78 to 100% (ICU) and 74 to 87% (PICU) in trials using an alternate/hybrid consent model.
Alternate consent models were used in the minority of Canadian-led ICU/PICU RCTs but have been used more frequently over the last decade. This suggests that Canadian ethics boards and research communities are becoming more accepting of alternate consent models in ICU/PICU trials.
Race, Place, and The Federal Exception from Informed Consent (EFIC): A Semiotic Approach [DISSERTATION]
Samantha Whitney Stein
The Exception from Informed Consent (EFIC) regulatory mechanism can be used to waive federal informed consent requirements for emergency medical research, pending satisfaction of pre-trial requirements. EFIC’s most notoriously challenging pre-trial requirement is ‘community consultation,’ a process through which EFIC researchers solicit public feedback on their trials. Using a Peircean semiotic framework, this thesis unpacks the presuppositions undergirding the idea that community consultation can reduce friction between emergency clinical trials carried out without informed consent and the values of patients enrolled in them. I introduce a semiotics of prediction, showing how assumptions about race figure prominently in the commensuration-based tasks of selecting community consultation respondents and subsequently generalizing findings from these respondents to broader populations. I suggest that in practice the content and / or generalizability of feedback collected through community consultation has very limited utility for reducing friction. Rather, community consultation’s primary function—as it is currently operationalized—is one of public relations, whereby the discursive processes through which community feedback is solicited have more bearing on EFIC trials’ public acceptability than the content of community feedback and the ability of biomedical research actors to transpose this content across contexts. By examining who participates in / is affected by the discursive processes through which community feedback is solicited, I help explain otherwise untheorized yet nonetheless troubling disparities between the acceptability of EFIC as determined by community consultation respondents and the acceptability of EFIC as determined by EFIC trial participants and their surrogates.
Characterization of Informed Consent Forms Posted on ClinicalTrials.gov
Tony Tse, Sarah White, Luke Gelinas, Walker Morrell, Barbara Bierer, Deborah A. Zarin
JAMA Network Open, 18 November 2021; 4(11)
Informed consent forms (hereinafter, forms), part of a larger consent process that serves multiple bioethical functions, are intended to provide potential research volunteers with sufficient written information about a clinical trial to help them decide about participation. Despite concerns about their overall quality, broadly generalizable samples of forms have been difficult to access for quality improvement. Since July 2017, ClinicalTrials.gov has allowed voluntary posting of forms for registered studies. Subsequently (January 21, 2019), the revised Common Rule form-posting requirement (45 CFR 46.116[h]) became effective (eAppendix in the Supplement). To explore how access to forms has increased on ClinicalTrials.gov after these initiatives, we sought to characterize registered trials with available forms and posting trends. We also assessed the frequency of form posting by funder type for trials initiated since the revised Common Rule compliance date…
As of July 7, 2021, forms were publicly available on ClinicalTrials.gov for nearly 2100 US trials for a range of intervention types and conditions from across 600 mostly nonindustry sponsors. Many of these trials (1243 of 2088 [59.5%]) did not list funding by a US federal agency and, among those 1243 trials, some were initiated before the compliance date, suggesting that their forms were likely not required to be posted under the revised Common Rule. The absolute percentages of federally funded trials initiated since the Common Rule compliance date in set 2 remain relatively low, with fewer than 87 of 529 trials (16.5%) listing a key funder type of “NIH” or “other US federal agency” having posted forms. Although forms for a range of trials are now available on ClinicalTrials.gov, most appear to have been posted voluntarily. Limitations of this cross-sectional study include that retrieved trials were likely skewed toward those required by federal reporting requirements. Trials may have also been miscategorized because of errors or incomplete information in data self-reported by study sponsors. Further research is needed because it is likely too soon to assess the full impact of the revised Common Rule requirement.
Informed consent in pragmatic trials: results from a survey of trials published 2014-2019
Jennifer Zhe Zhang, Stuart G Nicholls, Kelly Carroll, Hayden Peter Nix, Cory E Goldstein, Spencer Phillips Hey, Jamie C Brehaut, Paul C McLean, Charles Weijer, Dean A Fergusson, Monica Taljaard
Journal of Medical Ethics, 15 November 2021
To describe reporting of informed consent in pragmatic trials, justifications for waivers of consent and reporting of alternative approaches to standard written consent. To identify factors associated with (1) not reporting and (2) not obtaining consent.
Survey of primary trial reports, published 2014-2019, identified using an electronic search filter for pragmatic trials implemented in MEDLINE, and registered in ClinicalTrials.gov.
Among 1988 trials, 132 (6.6%) did not include a statement about participant consent, 1691 (85.0%) reported consent had been obtained, 139 (7.0%) reported a waiver and 26 (1.3%) reported consent for one aspect (eg, data collection) but a waiver for another (eg, intervention). Of the 165 trials reporting a waiver, 76 (46.1%) provided a justification. Few (53, 2.9%) explicitly reported use of alternative approaches to consent. In multivariable logistic regression analyses, lower journal impact factor (p=0.001) and cluster randomisation (p<0.0001) were significantly associated with not reporting on consent, while trial recency, cluster randomisation, higher-income country settings, health services research and explicit labelling as pragmatic were significantly associated with not obtaining consent (all p<0.0001).
Not obtaining consent seems to be increasing and is associated with the use of cluster randomisation and pragmatic aims, but neither cluster randomisation nor pragmatism are currently accepted justifications for waivers of consent. Rather than considering either standard written informed consent or waivers of consent, researchers and research ethics committees could consider alternative consent approaches that may facilitate the conduct of pragmatic trials while preserving patient autonomy and the public’s trust in research.
Simplifying consent – Use of the novel integrated consent model in paediatric clinical research
Frances Yeung, Saoirse Cameron, Sepideh Taheri
Paediatrics & Child Health, 29 October 2021; 26(Supplement 1) pp e82–e84
Obtaining informed consent from patients to participate in clinical research has traditionally been a cumbersome process, often requiring lengthy documentation and the involvement of trained research staff. Moreover, this process can be a burden to the patient/family. As a result, progress in paediatric research and enabling continual improvement in care has been slow. In the last decade, research ethicists have proposed a new “integrated consent model” (ICM) for obtaining informed consent for pragmatic clinical trials that compare standard-of-care interventions, where there is clinical equipoise. In most cases of ICM, only a brief discussion with verbal consent is required, along with a handout on study purpose, risks, benefits, and procedures. This allows for a more condensed consent process, which maximizes clarity and minimizes information overload. ICM also allows the patient/family to maintain prospective autonomy and decision-making, as compared with deferred or waived consent. The ICM model allows staff in the circle of care to obtain consent, which minimizes the stress of meeting an additional person. To our knowledge, ICM has not yet been used in the paediatric population.
The objective of this abstract is to report on the utility of ICM in a non-randomized clinical trial carried out in the inpatient setting of a tertiary children’s hospital.
We compared two widely accepted standards of care for maintaining peripheral intravenous catheter patency in a cohort of children, namely continuous infusion (“to keep the vein open” or TKVO) versus saline lock (SL). The ICM process was reviewed and approved by REB. Nurses in the circle of care received a study package that included an REB approved “consent script” to be read to the patient/family, a single page information sheet, and instructions on documenting the obtained verbal consent in the patient’s chart (Graphic 1).
With ICM, 79% of participants were recruited into the trial by a nurse. Patient recruitment was completed 4 months ahead of the predicted schedule (Figure 1). Nursing, research, and medical staff were satisfied with ICM and found it easy to administer. ICM occurred smoothly and quickly for patients/families, with no interference with their medical care and practically no disruption to their daily schedule.
ICM is a practical alternative to laborious traditional consent models, is associated with higher patient recruitment rates, and is less burdensome for the patient/family. Paediatricians should be aware of the utility of this novel consent model.
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
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.
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.
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.
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
Laura Gangeri, Sara Alfieri, Margherita Greco, Marta Scrignaro, Elisabetta Bianchi, Paolo Casali, Davide Ferraris, Claudia Borreani
Supportive Care in Cancer, 7 October 2021
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).
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.
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.
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
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
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.
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.
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.
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.