Advancing Randomized Clinical Trials in Surgery: Role of Exception From Informed Consent, Central Institutional Review Board, and Bayesian Approaches
Review
Amelia W. Maiga, Rebecca A. Snyder, Lillian S. Kao, Mehul V. Raval, Mayur B. Patel, Martin L. Blakely
Journal of Surgical Research, 25 April 2024
Introduction
…In order to address the unique challenges of designing and conducting randomized clinical trials in surgery, surgeon investigators from the Society of University Surgeons and the Association for Academic Surgery hosted a didactic session at the 2023 Academic Surgical Congress. In this paper, we summarize the key discussion points presented in this session and outline opportunities to promote the design of feasible and generalizable surgical RCTs. In particular, we will review the use of exception from informed consent (EFIC) in surgical trials, central institutional review board (IRB) review for multicenter trials, currently recommended statistical methods to increase clarity of trial findings and avoid dichotomy around the P value, and opportunities to incorporate Bayesian methods into study design and interpretation…

Participant Recruitment, Consent and Post-trial Access to Interventions
Book Chapter
Maru Mormina, Halina Suwalowska, Mira L. Schneiders
Research Ethics in Epidemics and Pandemics: A Casebook, 24 April 2024 [Springer]
Open Access
Abstract
Humanitarian emergencies, including public health crises such as epidemics, can overwhelm local resources and severely disrupt the functioning of communities and societies. Conducting research during or in the immediate aftermath of an emergency poses increased practical and ethical challenges, not least because the need to rapidly generate valuable knowledge must be constantly balanced with the principles of humanitarian assistance. This chapter provides an overview of key ethical considerations relevant to recruitment, consent and post-trial access to interventions in pandemic contexts, and proposes an “ethics in practice” approach. Research conducted during emergencies is unavoidably context – and time – sensitive, making generalized guidance difficult. The aim of this chapter is thus not to prescribe a checklist for decision-making, but to assist researchers and practitioners to reflect on and discern what constitutes ethical practice during exceptional times. In particular, public health emergencies highlight tensions that can arise between balancing the rights and interests of research participants with the health needs of the population. Careful consideration is also needed of the necessity of minimising risks and maximising benefits, including ensuring that recruitment processes are sensitive to potentially altered risk perceptions and impacts of increased vulnerability on power imbalances. The importance of establishing and maintaining trust is reviewed, particularly when asymmetries in knowledge and access to resources are heightened in complex and challenging pandemic contexts. The five case studies presented in this chapter invite readers to reflect on ethical challenges that research during public health emergencies presents, particularly in connection with processes for communicating with and recruiting participants which have been adapted in pandemic contexts; potential risks to research participants and study staff; and with the rights participants in control groups may have to access experimental products.

Individual consent in cluster randomised trials for non-pharmaceutical interventions: going beyond the Ottawa statement
Research Paper
Marissa LeBlanc, Jon Williamson, Francesco De Pretis, Jürgen Landes, Elena Rocca
Critical Public Health, 18 April 2024
Abstract
This paper discusses the issue of overriding the right of individual consent to participation in cluster randomised trials (CRTs). We focus on CRTs testing the efficacy of non-pharmaceutical interventions. As an example, we consider school closures during the COVID-19 pandemic. In Norway, a CRT was promoted as necessary for providing the best evidence to inform pandemic management policy. However, the proposal was rejected by the Norwegian Research Ethics Committee since it would violate the requirement for individual informed consent. This sparked debate about whether ethics stand in the way of evidence-based health policy, since the Norwegian Research Ethics law’s strict requirements for individual consent make it practically impossible to carry out CRTs of public health interventions. We argue that, in the case of the school closure trial, the suggested CRT would not have eliminated an epistemic gap and thus would not have justified the violation of consent rights. First, we focus on the methodological challenges to estimating quantifiable effects of school closures in the specific case of an airborne infectious disease. Second, in line with Evidential Pluralism, we highlight the value of alternative lines of evidence for informing school closure policy in a pandemic. In general, we propose that a trial requiring the waiver of participants’ consent rights must be highly likely to eliminate an epistemic gap. We elaborate on the practical aspects of this criterion and discuss the potential advantages of adding it to the Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials.

Analysis of informed consent documents for compliance with ICMR guidelines for biomedical and health research
Original Article
Chaitali Ashish Chindhalore, Ganesh N. Dakhale, Snehalata V. Gajbhiye, Ashish Vijay Gupta, Shivam V Khapeka
Perspectives in Clinical Research, 8 April 2024
Abstract
Background
Ethical conduct of research depends on the voluntary expression of consent and adequate disclosure of information about the research in informed consent documents (ICDs).
Objectives
The objective of this study was to analyze ICDs of academic studies for compliance with National Ethical Guidelines for Biomedical and Health Research laid down by the Indian Council of Medical Research (ICMR) and to determine the readability of ICDs using the Flesch–Kincaid Grade Level scale and Flesch reading-ease (FRE) score.
Methodology
ICDs of academic research projects submitted during 2020–22 were retrieved from the IEC office and analyzed for compliance with ICMR 2017 guidelines. The readability of the documents was assessed by the Flesch–Kincaid Grade Level Scale and FRE score.
Results
Among 177 protocols analyzed, the most common were epidemiological studies (36.72%), followed by diagnostic studies (28.81%). Vernacular translations of ICDs were present in significantly more studies in 2022 (χ2 = 7.18, P = 0.02) as compared to 2020 and 2021. FREs score was 45.75 ± 10.76, and Flesch–Kincaid Grade Level was 8.67 ± 1.44. Content analysis of participant information sheet (PIS) revealed that significantly more PIS submitted in 2022 mentioned expected duration of participation (χ2 = 6.95, P < 0.001), benefit to patient/community (χ2 = 26.63, P < 0.001), disclosure of foreseeable risk or discomfort (χ2 = 21.72, P < 0.001), payment for participation (χ2 = 21.72, P < 0.001), and identity of research team and contact details (χ2 = 18.58, P < 0.001). Compliance score was significantly better in 2022 as compared to 2020 and 2021.
Conclusion
Gradually, ICDs became more compliant with ICMR guidelines. Still, there is scope for improvement in ICDs regarding content and readability so that patients can comprehend facts easily to make informed decisions in a real sense.

Alternative consent methods used in the multinational, pragmatic, randomised clinical trial SafeBoosC-III
Research
Maria Linander Vestager, Mathias Lühr Hansen, Gorm Greisen, SafeBoosC-III trial group
Trials, 4 April 2024
Open Access
Abstract
Background
The process of obtaining prior informed consent for experimental treatment does not fit well into the clinical reality of acute and intensive care. The therapeutic window of interventions is often short, which may reduce the validity of the consent and the rate of enrolled participants, to delay trial completion and reduce the external validity of the results. Deferred consent and ‘opt-out’ are alternative consent methods. The SafeBoosC-III trial was a randomised clinical trial investigating the benefits and harms of cerebral oximetry monitoring in extremely preterm infants during the first 3 days after birth, starting within the first 6 h after birth. Prior, deferred and opt-out consent were all allowed by protocol. This study aimed to evaluate the use of different consent methods in the SafeBoosC-III trial, Furthermore, we aimed to describe and analyse concerns or complaints that arose during the first 6 months of trial conduct.
Methods
All 70 principal investigators were invited to join this descriptive ancillary study. Each principal investigator received a questionnaire on the use of consent methods in their centre during the SafeBoosC-III trial, including the possibility to describe any concerns related to the consent methods used during the first 6 months of the trial, as raised by the parents or the clinical staff.
Results
Data from 61 centres were available. In 43 centres, only prior informed consent was used: in seven, only deferred consent. No centres used the opt-out method only, but five centres used prior and deferred, five used prior, deferred and opt-out (all possibilities) and one used both deferred and opt-out. Six centres applied to use the opt-out method by their local research ethics committee but were denied using it. One centre applied to use deferred consent but was denied. There were only 23 registered concerns during the execution of the trial.
Conclusions
Consent by opt-out was allowed by the protocol in this multinational trial but only a few investigators opted for it and some research ethics boards did not accept its use. It is likely to need promotion by the clinical research community to unfold its potential.