Clinical trials in the time of a pandemic: Implications for informed consent
L. Palazzani
BioLaw Journal, 2021; Special Issue 2
Abstract
Focusing on clinical trials in the time of a pandemic, the contribution offers a comprehensive overview of the main challenges for investigators-physicians and patient-participants, discussing their ethical implications for the informed consent. Namely, adaptive and pragmatic trial designs can balance the rapidly changing standards of care with speed and agility, but these are designs which encompass specific implications for the informed consent process; the move towards the use of off-label drugs and compassionate pharmaceuticals in pandemics, which has been unavoidable due to the urgency of treating patients and the lack of knowledge on the virus, on the other hand raises many ethical questions that should be carefully addressed; the impact of the pandemic on ongoing clinical trials and on new trials, due to Covid-19 restrictions, needs proper consideration as well. Moreover, the contribution discusses the ethical conditions for deferred consent and key elements of re-consent alongside with ethical issues related to an electronic-digital consent in the case of tele-medicine and remote information-monitoring. Finally, the article encompasses a focus on patients’ vulnerabilities, including specific vulnerabilities (age, gender and ethnicity) that should be protected in conducting clinical research.

Informed consent and group vulnerability in the context of the pandemic
F. Macioce
BioLaw Journal, 2021; Special Issue 2
Abstract
Group vulnerability is a standard issue in bioethics. Research ethics guidelines highlight the need for protection of vulnerable participants, and clinical trials are ruled by ethical and legal principles that concern possible health inequities experienced by vulnerable populations. In both the literature and the regulation, two conceptions of vulnerability are at work. On the one hand, the inherent vulnerability that is part of the human condition; on the other hand, the situational vulnerability that is associated with specific contextual factors, and that point out either a reduced autonomy or a greater risk of harms for individuals belonging to some groups. Both these two conceptions of vulnerability are exacerbated during a pandemic; on the one hand, specific populations are at heightened risk for medical complications from the virus (elderly, or immunodepressed);on the other hand, specific groups experience an increased vulnerability due to the social determinants of health, which influence individual resilience and exacerbate the impact of the virus. Among the many (income distribution, education and literacy, working condition, house and living conditions, disability, access to health services, etc.) the dramatic reduction of the space for free and informed consent, because of the mental and physical adverse effects coming from social isolation, age, culture, literacy, is relevant for both clinical research and practice. In this paper, I will discuss challenges for the informed consent in the context of the Covid-19 pandemic, with specific consideration of the condition of vulnerable groups.

Informed consent and artificial intelligence applied to RCT and Covid-19
E. Tozzi, G. Cinelli
BioLaw Journal, 2021; Special Issue 2
Abstract
Artificial intelligence (AI) tools allow to extract knowledge from big data and are increasingly used for research purposes applied to -omics, diagnostic images, complex patterns of diseases and system medicine, drug development, robotics, and other topics. The management of big data, largely made of individual clinical data, poses specific ethical challenges that must be addressed in research studies and that should be reflected in the informed consent process. Explaining the mechanisms used by AI algorithms in supporting clinical decision making may be particularly difficult because of the opacity of its process. Moreover, depending on the quality of data feeding their algorithms, AI applications may result in errors. As the General Data Protection Regulation (GDPR) includes the possibility that a patient withdraws his/her informed consent from a study, it may be challenging to update AI algorithms accordingly. On the other hand, AI tools may help support the recruitment and retention of participants in clinical trials matching eligibility criteria with individual data collected for clinical purposes in electronic health records, and improve data collection and analytics. The possibility to stream data from wearable devices offers the possibility to generate large data volumes relevant to Patient Reported Outcomes feeding AI predictive algorithms. The Covid-19 pandemic has promoted the application of digital tools and of AI in clinical trials in order to limit personal contacts. The pressure exerted by the pandemic will possibly speed up the adoption of AI solutions for clinical trials and will highlight their potential ethical implications.

Informed consent, clinical research, Covid-19 and contact tracing apps: Some neuroethical concerns
D. Garasic
BioLaw Journal, 2021; Special Issue 2
Abstract
The explosion of the Covid-19 pandemic has led us to introduce numerous states of exception in our everyday lives, sparking debates about their appropriateness at various levels. Among other changes we have adopted, there has been an increase of apps supporting our fight against Covid-19 all over the world. From apps helping us to join and coordinate clinical trials to contact tracing apps, various are the instances in which digital technology has -at least attempted to come to rescue to the scientific, public policy and political realms during the challenging times we are currently living in. Particularly in relation to contact tracing apps, ethical concerns have been raised over the level of transparency that they can guarantee, often stressing how the State needs to ensure a number of variables to be granted to citizens from privacy to fairness of access and distribution through their compulsory status or not. In Western liberal democracies, the assumption has been that all risks associated with this digital technology would have to be dealt with by the State – hence making its misuse “only” public, albeit authoritarian in their most dystopian versions. Here, the intention is to stress some of the overlooked dimensions of the use of different types of Covid-19 related apps. More specifically, this paper takes issue with the secondary use of data that various private companies engaged in the fight against Covid-19 could make -with an unclear role for informed consent. Especially when in the hands of private, for profit, companies, attention should abound on what states of exceptions we are allowing to slip through our ethical supervision -and to what we are actually giving consent to when downloading these apps.

Informed consent for clinical research in the context of the Covid-19 pandemic between bioethics and biolaw: A general overview
Palazzani
BioLaw Journal, 2021; Special Issue 2
Abstract
The article examines the transformations of informed consent in the context of the Covid-19 pandemic, analyzing the bioethical discussion and in particular the national and international documents relevant to bioethical and biolegal issues, in both institutional bodies and bioethics committees. Informed consent is analyzed in the context of experimentation with treatments and vaccines, the use of biological samples and the processing of personal data.

Ethical and regulatory issues in vaccine research in the pandemic context and in the case of human challenge studies: Implications for informed consent
Daverio
BioLaw Journal, 2021; 2 pp 63-84
Abstract
In the pandemic context several specificities should be underlined for the case of vaccine trials, in addition to all ethical concerns raised for research related to pharmacological treatments which are also valid for vaccine research. Study population in vaccine trials is built up with healthy volunteers that should be carefully and fairly selected; as far as vaccine for emergency use are approved, the use of placebo in controlled studies raises ethical questions that should be discussed. Participants in vaccine trials should in any case be unduly influenced by any form of payment, and the gratuity of their act should be stressed in the communication and consent process. Moreover, in the context of experimentation with vaccines, sensitive ethical issues can arise also from the so-called “challenge studies”, since they concern intentionally infecting healthy people to investigate diseases and their treatments (human challenge trials involve exposing healthy volunteers to a pathogen to learn more about the disease it causes and to test vaccines quickly). The contribution finally includes a specific list of aspects to be included in well-designed information and consent process for participants’ in vaccine research in the Covid-19 pandemic.

A literature review of consent declines and consent withdrawals in randomized controlled trials conducted during the COVID-19 pandemic
Original Article
NJ Gogtay, HJ Sheth, MR Maurya, MN Belhekar, UM Thatte
Journal of Postgraduate Medicine, 16 August 2021; 67(3) pp 134-138
Abstract
Objectives
We evaluated the extent of consent declines and consent withdrawals during the COVID-19 pandemic as seen in published randomized controlled trials (RCTs) and compared it with non-COVID-19 RCTs published at the same time and two historical controls.
Methods
PubMed/Medline only was searched using key-word “COVID-19” and “RCTs” separately, and filtered for COVID-19 RCTs and non-COVID-19 RCTs respectively, published during a nine-month period (1 Feb – 1 Nov 2020). Exclusions were study protocols, observational studies, interim analysis of RCT data and RCTs with missing data. Primary outcome measures were the proportion of consent declines and consent withdrawals as percentage of total participants screened and randomized respectively in COVID-19 RCTs. We compared consent declines and consent withdrawals of COVID-19 RCTs with non-COVID-19 RCTs and two earlier studies on the same topic that served as historical controls (non-pandemic setting).
Results
The search yielded a total of 111 COVID-19 RCTs and 49 non-COVID-19 RCTs. Of these, 39 (35.13%) COVID-19 RCTs and 11 (22.45%) non-COVID-19 RCTs were finally analysed. A total of 770/17759 (4.3%) consent declines and 100/7607 (1.31%) consent withdrawals were seen in 39 COVID-19 RCTs. A significant difference was observed in consent declines between COVID-19 vs non-COVID-19 RCTs [4.3% vs 11.9%, p < 0.0001] and between COVID-19 RCTs vs two historical controls [(4.3% vs 8.6%, p < 0.0001) and (4.3% vs 21.1%, p < 0.0001), respectively].
Conclusion
RCTs conducted during the COVID-19 pandemic appear to have significantly lower consent declines relative to non-COVID-19 RCTs during pandemic and RCTs conducted in non-pandemic settings.

Informed consent and informed intervention: SARS-CoV-2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing
Letter to the Editor
Johannes C. Fischer, Albrecht G. Schmidt, Edwin Bölke, Verena Keitel, Torsten Feldt, Björn Jensen, Noemi F. Freise, Dieter Häussinger, E. Marion Schneider, Derik Hermsen, Detlef Kindgen-Milles, Wolfram Trudo Knoefel, Jan Haussmann, Balint Tamaskovics, Christian Plettenberg, Kathrin Scheckenbach, Stefanie Corradini, Jutta Rox, Vera Balz, Kitti Maas, Livia Schmidt, Olaf Grebe, Anja Erhardt, Peter Arne Gerber, Matthias Peiper, Bettina Alexandra Buhren, Artur Lichtenberg, Amir Rezazadeh, Wilfried Budach, Christiane Matuschek
European Journal of Medical Research, 6 August 2021; 26(87)
Open Access
Abstract
Background
COVID-19 infection is a major threat to patients and health care providers around the world. One solution is the vaccination against SARS-CoV-2.
Methods
We performed a comprehensive query of the latest publications on the prevention of viral infections including the recent vaccination program and its side effects.
Results
The situation is evolving rapidly and there is no reasonable alternative to population-scale vaccination programs as currently enrolled.
Conclusion
Therefore, regulatory authorities should consider supplementing their conventional mandate of post-approval pharmacovigilance, which is based on the collection, assessment, and regulatory response to emerging safety findings.

Anti-Coronavirus Disease 2019 Vaccines: Need for Informed Consent.
Mazraani M, Barbari A
Experimental and Clinical Transplantation, 1 August 2021; 19(8) pp 753-762
Abstract
Vaccines are among some of the most efficacious medical and public health methods ever employed to contain a pandemic, in addition to providing protective and preventive measures. Evaluation of vaccine associated adverse events through experimentation and empirical evidence is an integral part of thoroughly assessing the safety of vaccines before authorization of their widespread use. History has highlighted the importance of continuous search for possible vaccine-related adverse effects and vaccine-induced immunogenicity long after licensure, suggesting that a primary concern with new vaccines is not only efficacy but also safety, particularly over the long term. Many of the various anti-COVID-19 vaccines have used different types of technology, with some being introduced for the first time or rushed shortly into testing, bypassing animal experimentations. They have been adopted for use through emergency use authorizations, leading to a less than optimal collection of broad data on safety, immunogenicity, effectiveness, and time span of protection, as well as short follow-up of few months, despite many infectious disease experts arguing that it takes 10 years to develop a vaccine. Given the valid concerns on well-recognized short-term and long-term safety issues, such as antibody-dependent enhancement and other processes like molecular mimicry and potential genomic transformation, the experimental nature of the vaccination process, the limited short term follow-up in the main trials, and the dismissal by law of pharma companies and health care providers from any medico-legal responsibilities, the application of an informed consent should become not only a necessity but also mandatory by law in accordance with all declarations on human rights. Such information should be provided to every potential recipient in the form of an official written digital consent prior to the registration for or the receipt of the vaccine.

Editor’s note: Experimental and Clinical Transplantation is the official journal of the Middle East Society for Organ Transplantation.

How Spanish Biobanks have Adapted the Informed Consent Process During the COVID-19 Pandemic
Pablo Enguer-Gosálbez, Jaime Fons-Martínez, Jacobo Martínez-Santamaría, Ana María Torres-Redondo, Cristina Villena-Portella, Aurora García-Robles, Javier Díez-Domingo
BioLaw Journal, 2021
Open Access
Abstract
Due to the situation caused by the Covid-19 pandemic, biobanks have adapted, among other processes, the obtaining of informed consents (IC). This paper details the most relevant elements of the applicable regulations, describes the adaptations done by some of the biobanks of the Spanish Biobank Network to manage the IC process, which have been approved by their Ethics Committees, and draws some conclusions from the results obtained from the survey carried out on these biobanks.