French pediatricians' views on industry-sponsored clinical trials: Toward stronger research on ethics?

INTRODUCTION: There is a crucial need to perform clinical trials in pediatrics due to an increased prescription rate of unapproved drugs. Since pediatricians are the gatekeepers of clinical trials, the primary objective of the current study was to evaluate, for the first time in France, pediatricians' views on performing clinical trials. The second objective was to identify the factors that influence their perceptions. MATERIAL AND METHODS: In 2017, pediatricians who were members of the French Pediatric Society completed an online survey comprising 27 questions. Fisher's exact test was performed to evaluate possible correlations between pediatrician characteristics (age, sex, parenthood, professional experience, status, type of practice, previous participation in clinical trials, ethics education) and personal views on clinical trials. A value of P≤0.001 was considered statistically significant. RESULTS: Overall, 207 pediatricians completed the questionnaire. Almost all participants (96.6%) were in favor of performing clinical trials. Pediatricians with teaching experience at university hospitals were more reluctant to propose children's participation in clinical trials for fear of increasing parental stress (P<0.001), or the occurrence of serious adverse reactions (P<0.001). Pediatricians with coordinator or investigator experience considered that one of the ethical drifts in pediatric clinical trials is the risk of child exploitation (P<0.001). CONCLUSION: Our findings suggest a favorable position of pediatricians concerning clinical trials, despite numerous concerns. Another outcome is the need to create an educational system of research in ethics in France dedicated to pediatricians in order to guarantee good clinical practice in research.

Ethical conflicts in COVID-19 times.

The COVID-19 pandemic has created new challenges on multiple fronts including a few ethical concerns. Timely and appropriate access to health services and the need to protect vulnerable people are some of them. An important aspect to consider, at the global level, is the frailty of health systems in many developing countries and the constant threat of these collapsing due to shortage of resources and medical supply. Special attention should be placed towards protecting the health of care workers who are highly exposed to SARS-CoV-2 infection. Research and clinical trials involving COVID-19 patients and healthy human volunteers must be done in strict adherence to the fundamental principles of bioethics, even if finding a solution is an urgent need. Shared responsibility must be assumed as we collectively face a common problem and ethical conflicts must be resolved using, as reference, the guidelines developed by the World Health Organization and other relevant international and national organizations. This would allow responsible action in the face of the pandemic without harming human rights, the individual and collective well-being.

Expedited COVID-19 vaccine trials: a rat-race with challenges and ethical issues.

The intense global efforts are directed towards development of vaccines to halt the COVID-19 virus pandemic. There are 160 candidate vaccines under clinical trials across the world using different molecular targets and techniques. This race for the vaccine has several challenges and ethical issues like compressed timelines, generation and proper management of resources and finances, risks to the participating volunteers due to curtailed research trial processes, geopolitical contentions, misinformation through social media and parallel race with drugs. We feel that the fundamental principles of ethics: autonomy, beneficence, non-maleficence and justice should not be violated in this hastened vaccine development process. We recommend constitute a Consortium on a global platform to formulate, provide and monitor a comprehensive ethical umbrella to the process of vaccine development.

Ethical review of patient safety and public health in EU clinical trials legislation: impact of COVID-19 pandemic.

PURPOSE: The study considers the ethical review of the European Union (EU) clinical trials (CTs) legislation, namely the Clinical Trials Regulation (CTR) (EU) 2014∕536, the Directive 2001∕20∕EC and the "Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic" (GMCT) (version 3) issued on 28 April 2020 by the European authorities in the field. BACKGROUND: The Directive 2001∕20∕EC focuses the legal provisions for the conduct of CTs by acknowledging the screening role of the Ethics Committees (ECs) and of the national competent authorities (NCA) in the Member States (MS) to protect the CT subject and the personal data. CONTENT: The present article displays the ethical requirements for conducting, monitoring and reporting of the CTs by raising awareness on the: (i) new conceptual framework of the "clinical trial", "low-intervention clinical trial", "non-interventional study" and "ethics committee"; (ii) ethical considerations addressed in Part I and Part II of the assessment report; (iii) evaluation of the coronavirus disease 2019 (COVID-19) pandemic on the current regulatory framework. CONCLUSIONS: The CTR stimulates the EU clinical research and enables an independent control with regard to the respect of the interests of the CT subject.

Pregnant Women in Trials of Covid-19: A Critical Time to Consider Ethical Frameworks of Inclusion in Clinical Trials.

Ethical issues abound during this unprecedented international public health crisis of Covid-19. While the trade-off between societal and individual interests that occurs at the intersection of public health ethics and clinical ethics affects all populations, this calculus has particular relevance for pregnant women and the question of when they will have access to new Covid-19 therapies and vaccines. Pregnant women are a "scientifically complex" population whose inclusion in clinical research must be done with consideration of the unique state of pregnancy. Yet research on the impact of Covid-19 on pregnant women is lagging. In a rush to prevent and treat SARS-CoV-2 infection, it is crucial that the interests of pregnant women be prioritized to enable them to make autonomous, informed decisions about participating in clinical trials. The global pandemic calls for a revisiting of frameworks for the inclusion of pregnant women in research, as these women have an important stake in the prevention and treatment of Covid-19.

[Participant-funded clinical trials on rare diseases]. / Ensayos clínicos en enfermedades raras financiados por los participantes.

The development of medicines for certain rare diseases can be frustrated by lack of funding. In certain cases the patients themselves, or their relatives, occasionally fund the clinical trial in which they will be treated with the investigational medicine. There are 3models of self-funded research: 2of them, "pay to try" and "pay to participate", have already been put into practice. The third, the "plutocratic" proposal, which has been recently put forward is still a theoretical model. In this work the scientific, social and ethical benefits and risks of the 2clinical research models, "pay to participate" and the "plutocratic" proposal, are reviewed. Patient-funded clinical trials are frequently performed through crowdfunding. The most controversial aspects of this funding modality are also addressed in this article from several perspectives. Finally, a future scenario that would allow the launching of self-funded clinical trials in Spain by the "plutocratic" proposal is proposed.

Stopping Clinical Trials in Inflammatory Bowel Disease During the COVID-19 Pandemic Is Not a Responsible Act.

The intense competition for resources to combat COVID-19 has greatly reduced access to health care for patients with other diseases. After the disastrous overrun of hospitals through COVID-19 patients in some jurisdictions, availability of resources for 'elective' medical procedures, including care for the chronically ill, has been greatly reduced in many places as a pre-emptive measure before or during the blooming of infection clusters. Pharmaceutical companies have either stopped recruitment or even cancelled ongoing clinical trials in chronic diseases. Pre-emptive triage and its impact on medical ethics is discussed in the framework of care for inflammatory bowel disease.

Regulatory oversight of cell therapy in China: Government's efforts in patient access and therapeutic innovation.

In recent years, remarkable progress has been made in the fundamental research and on clinical development of cell therapy. Although China has launched a series of regulations to establish a proper regulatory framework that facilitates the development of cell therapy products, the regulatory framework has not been able to meet the country's regulatory requirements. This article introduced the development of regulation and current regulatory pathways for cell therapy in China and identified the main challenges in clinical studies. China has recently tightened its policy on cell therapy clinical studies after medical chaos occurred in the area of cell therapy over the past few years. Currently the regulatory jurisdiction between NMPA and NHC are not very clear, especially for clinical somatic cell research, further efforts are necessary to establish a legislative system with a clear and functional regulatory framework for cell therapy.

Paying Participants in COVID-19 Trials.

Trials are in development and underway to examine potential interventions for treatment and prophylaxis of coronavirus disease 2019 (COVID-19). How should we think about offering payment to participants in these trials? Payment for research participation is ethically contentious even under ideal circumstances. Here, we review 3 functions of research payment-reimbursement, compensation, and incentive-and identify heightened and novel ethical concerns in the context of a global pandemic. We argue that COVID-19 trial participants should usually be offered reimbursement for research-related expenses, and compensation for their time and effort, as for other types of research under usual circumstances. Given increased risk of undue influence against pandemic background conditions, incentive payment should be avoided unless essential to recruitment and retention in important trials whose social value outweighs this risk. Where essential, however, incentives can be ethically permissible, so long as reasonable efforts are made to minimize the possibility of undue influence.

Ethical considerations for epidemic vaccine trials.

Vaccines are a powerful measure to protect the health of individuals and to combat outbreaks such as the COVID-19 pandemic. An ethical dilemma arises when one effective vaccine has been successfully developed against an epidemic disease and researchers seek to test the efficacy of another vaccine for the same pathogen in clinical trials involving human subjects. On the one hand, there are compelling reasons why it would be unethical to trial a novel vaccine when an effective product exists already. First, it is a firm principle of medical ethics that an effective treatment or vaccine should not be withheld from patients if their life may depend on it. Second, since epidemic outbreaks often emerge in settings with less-resourced health systems, there is a pronounced risk that any trial withholding an effective vaccine would disproportionately affect the vulnerable populations that historically have been exploited for biomedical research. Third, clinical trials for novel vaccines may be at odds with efforts to control active outbreaks. On the other hand, it may be justified to conduct a trial for a candidate vaccine if it is expected to have certain advantages compared with the existing product. This essay discusses key factors for comparing vaccines against epidemic pathogens, including immunological, logistical and economic considerations. Alongside a case study of the development of vaccines for Ebola, the essay seeks to establish a general framework that should be expanded and populated by immunologists, epidemiologists, economists and bioethicists, and ultimately could be applied to the case of COVID-19 vaccines.

Designing clinical trials for future space missions as a pathway to changing how clinical trials are conducted on Earth.

OBJECTIVE: The project aims to build a framework for conducting clinical trials for long-term interplanetary missions to contribute to innovation in clinical trials on Earth, especially around patient involvement and ownership. METHODS: We conducted two workshops in which participants were immersed in the speculative scenario of an interplanetary mission in which health problems emerged that required medical trials to resolve. The workshops used virtual reality and live simulation to mimic a zero-gravity environment and visual perception shifts and were followed by group discussion. RESULTS: Some key aspects for the framework that emerged from the workshops included: (a) approaches to be inclusive in the management of the trial, (b) approaches to be inclusive in designing the research project (patient preference trials, n-of-1 trials, designing clinical trials to be part of a future prospective meta-analysis, etc), (c) balancing the research needs and the community needs (eg, allocation of the participants based on both research and community need), (d) ethics and partnerships (ethics and consent issues and how they relate to partnerships and relationships). CONCLUSION: In identifying some key areas that need to be incorporated in future planning of clinical trials for interplanetary missions, we also identified areas that are relevant to engaging patients in clinical trials on Earth. We will suggest using the same methodology to facilitate more in-depth discussions on specific aspects of clinical trials in aerospace medicine. The methodology can be more widely used in other areas to open new inclusive conversations around innovating research methodology.

The Northwestern Abdominoplasty Scar Model: A Tool for High-Throughput Assessment of Scar Therapeutics.

Significance: Scar management is an important concern in plastic surgery. Scar models that best mimic in vivo human scarring are essential for understanding scar development and progression, assessing the efficacy of therapeutics, and providing reliable and valid research outcomes. Recent Advances: In 2016, Lanier et al. proposed a new in vivo patient model, the Northwestern Abdominoplasty Scar Model, that overcomes the prior limitations of both animal and human models, with greater representativeness of the human scarring process, expedited recruitment, smaller sample requirements, and greater flexibility in the types and number of interventions that can be studied simultaneously. Critical Issues: Existing animal models suffer from limitations that impede generalization to human scars. Human scar studies are difficult to conduct and rarely used due to recruitment difficulties, ethical concerns regarding purposeful wounding, and inherent variability based on location, type of scar, and the heterogeneity of the host response between humans. Although overcoming many of these hurdles, the Northwestern Abdominoplasty Scar Model still has a few limitations. In addition, there remains a need for further study of and comparison between the Northwestern Abdominoplasty Scar Model and existing human and animal models, to inspire more widespread acceptance of a standardized human scar model. Future Directions: The Northwestern Abdominoplasty Scar Model is a critical stepping stone toward better human scar models. This model hopefully will inspire other in vivo patient models utilizing elective surgery to overcome recruitment and ethical concerns.

Regulatory changes after the enforcement of the new Clinical Trials Act in Japan.

OBJECTIVE: To describe changes in Japanese clinical trial regulations after the implementation of the Clinical Trials Act in April 2018. METHODS: First, how to apply multiple regulations after the enforcement of Clinical Trials Act was described. Second, the changes in the number of clinical trials in the National Cancer Center Hospital under each regulation were compared before and after the implementation of Clinical Trials Act. Third, new requirements imposed by Clinical Trials Act and their influences were discussed. RESULTS: In April 2018, Clinical Trials Act was enacted and academic clinical trials were classified into the following three categories: (i) investigator-initiated registration-directed trial under the Pharmaceuticals and Medical Devices Act; (ii) clinical trial under Clinical Trials Act; and (iii) clinical trial under the Ethical Guidelines. While 90% (205/227) of interventional studies were conducted under the Ethical Guidelines before the implementation of Clinical Trials Act in 2018, 46% (94/204) were subject to Clinical Trials Act in 2019 at the National Cancer Center Hospital. Under the Clinical Trials Act, investigators receive a scientific/ethical review by a certified review board (CRB). The identification of investigators in charge is mandated and they are required to submit the conflict of interest management plan to CRB. After the CRB review, the principal investigator must submit the trial plan to the government, and the content is uploaded to the newly established clinical trial registry site, the Japan Registry of Clinical Trials. CONCLUSIONS: The enforcement of the new Clinical Trials Act was supposed to improve the reliability of academic clinical trials in Japan; however, the financial and administrative burden may reduce clinical trial activity in the years to come.