Ethics of DNA Vaccine Transfer for Clinical Research.

Several experimental human DNA vaccines are currently undergoing Phase I, II, and III clinical trials in order to investigate their efficacy and safety. Human clinical trials must follow guidelines and procedures that have been approved by the regulatory authorities and ethics committees. Ethical clinical research is much more than applying an informed consent to participants. In this chapter we will review the ethical standards and provide a framework to evaluate and design ethical clinical research. Despite being universal standards supported by universal guidelines, they must be adapted to the conditions in each country where the clinical research is being conducted.

Reporting of prior clinical studies in Investigator's Brochures did not adhere to the basic principles of evidence synthesis: a cross-sectional study.

OBJECTIVES: International regulations require Investigator's Brochures (IBs) to compile all available evidence that inform the risk-benefit assessment for the newly planned clinical trial. This study examined the adherence of IBs to the basic principles of evidence synthesis when compiling prior clinical studies. STUDY DESIGN AND SETTING: For 97 IBs for phase I/II trials reviewed at one German research ethics committee we assessed the reporting on search, appraisal, and synthesis procedures for prior clinical studies. For a random subsample of 30 IBs, we evaluated the quality of reporting of the compiled 247 prior clinical studies. RESULTS: Only 2% of all 97 IBs reported a comprehensive search strategy, provided a critical appraisal of the compiled prior clinical studies or presented respective study results in a structured manner. For the 247 prior clinical studies compiled in 30 IBs, the information required to appraise their risk of bias (eg, sample size calculation or baseline characteristics) was rarely reported. CONCLUSION: When compiling all available evidence supporting the rationale for the proposed clinical study IBs do not acknowledge the broadly established principles for reviewing and reporting evidence. This may impact negatively on the trustworthiness and efficiency of risk-benefit assessment.

Ethical Challenges in Clinical Research During the COVID-19 Pandemic.

The sudden emergence of the COVID-19 pandemic brought global disruption to every aspect of society including healthcare, supply chain, the economy, and social interaction. Among the many emergent considerations were the safety and public health of the public, patients, essential workers, and healthcare professionals. In certain locations, clinical research was halted-or terminated-in deference to the immediate needs of patient care, and clinical trials focusing on the treatment and prevention of coronavirus infection were prioritized over studies focusing on other diseases. Difficult decisions were made rapidly; flexibility and reconsideration were necessary not only because the intensity and severity of infection varied over time and by locale but also because knowledge of the disease and understanding of its treatment (and prevention) grew. Here we discuss the ethical challenges in decision-making and competing ethical tensions during the pandemic in an effort to advance future preparedness.

Informed consent procedures for emergency interventional research in patients with traumatic brain injury and ischaemic stroke.

Health-care professionals and researchers have a legal and ethical responsibility to inform patients before carrying out diagnostic tests or treatment interventions as part of a clinical study. Interventional research in emergency situations can involve patients with some degree of acute cognitive impairment, as is regularly the case in traumatic brain injury and ischaemic stroke. These patients or their proxies are often unable to provide informed consent within narrow therapeutic time windows. International regulations and national laws are criticised for being inconclusive or restrictive in providing solutions. Currently accepted consent alternatives are deferred consent, exception from consent, or waiver of consent. However, these alternatives appear under-utilised despite being ethically permissible, socially acceptable, and regulatorily compliant. We anticipate that, when the requirements for medical urgency are properly balanced with legal and ethical conduct, the increased use of these alternatives has the potential to improve the efficiency and quality of future emergency interventional studies in patients with an inability to provide informed consent.

The Consent Form in the Chinese CRISPR Study: In Search of Ethical Gene Editing.

This editorial provides an ethical analysis of the consent materials and other documents relating to the recent creation and birth of twin girls who had their genes edited using CRISPR-cas9 in a controversial Chinese research study. It also examines the "draft ethical principles" published by the leader of the research study. The results of the analysis further intensify serious ethical concerns about the conduct of this study.

Deferred consent for delivery room studies: the providers' perspective.

OBJECTIVE: To gain insight into neonatal care providers' perceptions of deferred consent for delivery room (DR) studies in actual scenarios. METHODS: We conducted semistructured interviews with 46 neonatal intensive care unit (NICU) staff members of the Leiden University Medical Center (the Netherlands) and the Hospital of the University of Pennsylvania (USA). At the time interviews were conducted, both NICUs conducted the same DR studies, but differed in their consent approaches. Interviews were audio-recorded, transcribed and analysed using the qualitative data analysis software Atlas.ti V.7.0. RESULTS: Although providers reported to regard the prospective consent approach as the most preferable consent approach, they acknowledged that a deferred consent approach is needed for high-quality DR management. However, providers reported concerns about parental autonomy, approaching parents for consent and ethical review of study protocols that include a deferred consent approach. Providers furthermore differed in perceived appropriateness of a deferred consent approach for the studies that were being conducted at their NICUs. Providers with first-hand experience with deferred consent reported positive experiences that they attributed to appropriate communication and timing of approaching parents for consent. CONCLUSION: Insight into providers' perceptions of deferred consent for DR studies in actual scenarios suggests that a deferred consent approach is considered acceptable, but that actual usage of the approach for DR studies can be improved on.

Evaluación de estudios de intervención por un Comité de Ética de la Investigación / Evaluation of intervention studies by a Research Ethics Committee

Los estudios experimentales con intervenciones diferentes a los ensayos clínicos con medicamentos o con productos sanitarios se regulan por la Ley 14/2007, de 3 de julio, de Investigación biomédica, que establece que toda investigación biomédica que comporte algún procedimiento invasivo en el ser humano deberá recogerse en un proyecto de investigación que será evaluado previamente por el Comité de Ética de la Investigación correspondiente. El objetivo de este trabajo es analizar los principios éticos y legales aplicables a la realización de los estudios de intervención y revisar los criterios de evaluación de este tipo de proyectos por un Comité de Ética de la Investigación

Experimental studies with interventions which are different than clinical trials with medicines or health products are regulated by Law 14/2007, of 3 July, on Biomedical Research, which establishes that all biomedical research involving an invasive procedure in human beings must be included in a research project that will be previously evaluated by the corresponding Research Ethics Committee. The aim of this work is to analyse the ethical and legal principles applicable to the carrying out of intervention studies. Likewise, the purpose of this paper is to review the criteria for evaluating this type of project by a Research Ethics Committee

A qualitative study on stakeholders' views on the participation of pregnant women in the APOSTEL VI study: a low-risk obstetrical RCT.

BACKGROUND: Bioethicists argue that inclusion of pregnant women in clinical research should be more routine to increase the evidence-base for pregnant women and foetuses. Yet, it is unknown whether pregnant women and others directly involved are willing to be routinely included. Therefore, we first need to establish what these stakeholders think about research participation in regular pregnancy-related research. However, studies on their views are scarce. In our study, we piggy-backed on a relatively conventional RCT, the APOSTEL VI study, to identify the views of stakeholders on inclusion of pregnant women in this study. METHODS: We conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed pregnant women (n = 14) recruited for the APOSTEL VI study, in addition to healthcare professionals (n = 14), Research Ethics Committee members (RECs) (n = 5) and regulators (n = 7) involved in clinical research in pregnant women. RESULTS: Three themes characterise stakeholders' views on inclusion of pregnant women in the APOSTEL VI study. Additionally, one theme characterises stakeholders' interest in inclusion of pregnant women in clinical research in general. First, pregnant women participate in the APOSTEL VI study for potential individual benefit and secondarily for altruistic motives, contrary to hypothetical studies. Second, a gatekeeping tendency hampers recruitment of pregnant women who might be eligible and willing, and questions about pregnant women's decisional capacities surface. Third, healthcare professionals sometimes use the counselling conversation to steer pregnant women in a direction. Fourth, all stakeholders are hesitant about inclusion of pregnant women in clinical research in general due to a protective sentiment. CONCLUSIONS: Pregnant women are willing to participate in the APOSTEL VI study for potential individual benefit and altruistic motives. However, an underlying protective sentiment, resulting in gatekeeping and directive counselling, sometimes hampers recruitment in the APOSTEL VI study as well as in clinical research in general. While bioethicists claim that inclusion of pregnant women should be customary, our study indicates that healthcare professionals, regulators, RECs and pregnant women themselves are not necessarily interested in inclusion. Advancing the situation and increasing the evidence-base for pregnant women and foetuses may require additional measures such as investing in the recruitment and feasibility of RCTs and stimulating pregnant women's decisional capacities.

Charting Regulatory Stewardship in Health Research: Making the Invisible Visible.

This section focuses on the ethical, legal, social, and policy questions arising from research involving human and animal subjects.

Moving targets: The challenges of studying infectious diseases among pregnant women in resource limited settings.

Conducting clinical trials to prevent and treat infectious diseases in pregnancy is essential to saving maternal and newborn lives, though it is fraught with challenges. We have been conducting research in malaria treatment and prevention in children and pregnant women in Blantyre, Malawi for over a decade. Here, we review some of the unique challenges that we have faced in leading research studies that with rigor and integrity and maintaining the highest ethical standard. We conclude with concrete strategies to overcome some of the apparent obstacles that frequently focus on building trust through bidirectional communication with local health workers and communities. We also highlight the key role of local and international investigators to advocate for the health of the communities in which they work.

Protecting boundaries of consent in clinical research: implications for improvement.

Successful clinical research outcomes are essential for improving patient care. Achieving this goal, however, implies an effective informed consent process for potential research participants. This article traces the development of ethical and legal requirements of informed consent and examines the effectiveness of past and current practice. The authors propose the use of innovative monitoring methodologies to improve outcomes while safeguarding consent relationships and activities. Additional rigorous research will help direct policy efforts at standardizing quality improvement processes.