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Abstract Our study describes the reported rate of the Institutional Review Board (IRB) approval, declaration of Helsinki (DoH), and informed consent in the case reports and case series and investigates factors associated with the ethical approval report. We searched PubMed for case reports and case series from 2006 to 2017. Annually, we obtained the first 20 articles of a case report cluster from 20 distinct publications. This analysis initially contained at least 2400 papers, with 100 papers each study design and year. Only 26 (5.4%) of 480 included studies reported IRB approval, DoH approval, and participant informed consent; 58 (12.1%) reported two out of three ethical statements (DoH, informed consent, IRB); and 151 (31.5%) reported only one, leading to nearly 245 studies (51.0%) did not report any ethical approval item. Both clusters mentioned the DoH the least. Only years, ages, ethical item types, and cluster types were associated with ethical reporting practices. This study found the serious under‐reporting of ethical practices in both case reports and case series.

Animal experimentation is a critical component of scientific research, offering insights into disease mechanisms, drug development, and treatment efficacy. However, ethical considerations surrounding the use of animals in research have prompted the establishment of regulations and guidelines worldwide. This article examines the multifaceted challenge of navigating regulations and ethical considerations in animal experiments, considering perspectives from international laws, Indian regulations, and Hinduism. It discusses the tension between the scientific imperative for research advancement and the ethical imperative to minimize harm to animals and uphold their welfare. International guidelines, such as the Three Rs principles, provide a framework for ethical conduct, emphasizing the Replacement, Reduction, and Refinement of animal use. In India, the Committee for Control and Supervision of Experiments on Animals regulates animal research, prioritizing animal welfare and requiring Institutional Animal Ethics Committees for oversight. Hinduism emphasizes principles of ahimsa (nonviolence) and compassion toward all living beings, influencing ethical perspectives on animal experimentation. Balancing scientific and ethical considerations requires careful consideration of alternative methods, reduction of animal usage, and refinement of experimental techniques. Cultural sensitivities, including those rooted in Hinduism, shape attitudes toward animal research and inform ethical practices. Collaborative efforts among researchers, policymakers, ethicists, and religious leaders are essential to promote responsible and ethical conduct in animal experiments while advancing scientific knowledge.

The vulnerability of research participants is a critical topic for the 2024 revision of the Declaration of Helsinki, with the proposal to include “social value. ” However, this proposal has been withdrawn and the relationship between the two concepts has not been clarified. This paper attempts to clarify: (1) the recent reform for the ethical inclusion of vulnerable study participants to promote diversity; (2) the social value, prerequisite for everyone, especially for those who are vulnerable and the most in need; (3) the requirements for promoting the inclusion of vulnerable participants, in particular the review of the norms for placebo-controlled trials and post-trial access; (4) finally, the direction of research ethics reform to achieve social value and equitable global health.

The World Medical Association has announced that a new revision process of the Declaration of Helsinki has been started. This article will identify the criticisms that have been made in the bioethics literature, particularly since the last revision. In addition, criticisms are discussed that were made in the literature even before the last revision and have not fallen silent. The plausibility of the recommendation for a change in the Declaration of Helsinki is examined. [ABSTRACT FROM AUTHOR]

Patient safety in surgical settings is an integral part of the further sustainable development of medicine in Ukraine. This is key in times of the war and post-war state when the budget deficit at all levels of public administration and health care is significant and may grow significantly in the future. Medical errors during anesthetic management and surgery are particularly costly and significantly burden the health care system. Even the wealthiest economies cannot afford such mistakes. The price is particularly high for Ukrainian realities, and these mistakes are fatal for our health care. For this review, the authors used the electronic databases MEDLINE and Embase. 15 studies were included in the review. A part of the data was also included from the department research. Demonstration of own results is limited, as the data have already been published in other publications or materials are in the reviewing process. Basic monitoring according to the WHO standards / World Federation of Societies of Anesthesiologists (WFSA) is mainly used in hospitals of European Union countries. Results are close to 100 % for pulseoximetry and blood pressure, 98 % for electrocardiography, and 96 % for capnography. In Ukraine, monitoring methods do not have critical differences, except for a slightly lower (73.7 %) spread of capnography and ECG monitoring (83.4 %). The situation is less encouraging in the context of regional anesthesia. In Ukraine, the situation is much worse. According to the survey conducted by our department, ultrasound navigation is available in only 67 % of hospitals. There is also a low level of taking safety measures, which include checklists, training, and clinical analyzes of errors. Conclusions. According to the data of this literature review, the components of the Declaration of Helsinki on safety in anesthesiology are gradually being implemented in Ukraine, the use of the WHO checklist “Safe surgery” and safety standards of regional anesthesia is spreading. The main directions for further development are the education of physicians and other staff on patient safety, the approval of national standards and monitoring of their implementation in practice, the creation of a notification and audit system for complications and critical incidents during anesthesia.

Anatomy has always been at the intersection of the socio‐cultural and political landscape, where new ideas constantly replace older wisdom. From ancient Egyptians through the Greeks, and then the Romans, finally culminating into the European Renaissance—all the significant eras of human civilisation have left their insignia and distinct marks on the evolution of anatomical practices. Despite its utility as a tool for anatomy pedagogy and research that has proven its worth over millennia, cadaveric dissection has particularly been subject to political and social vicissitudes. A major debate about anatomical dissection lay with the ethical considerations, or its lack thereof, while acquiring corpses for demonstration in the dissection halls. From antiquity, anatomical dissection—often synonymous with medical studies—had typically been carried out on the dead bodies of executed criminals with certain laws, such as the Murder Act of 1752, facilitating such uses. Gradually, the uses of unclaimed bodies, resourced primarily from the impoverished sections of society, were also introduced. However, these body acquisition protocols often missed the crucial element of humanism and ethical considerations, while knowledge augmentation was taken as sufficient reasoning. Unfortunately, a gross disregard towards humanistic values promulgated heinous and illegal practices in acquiring corpses, including grave robbery and even murders like in the case of Burke and Hare murders of 1828. Follow‐up legislation, such as the Anatomy Act of 1832, and comparable laws in other European nations were passed to curb the vile. What distils from such a historical discourse on humane values in anatomy dissection, or medical science in general, is that the growth and integration of humanism in anatomy have never been linear, but there were intermittent and, yet, significant disruptions in its timeline. For example, there were serious human rights violations in anatomical practices during the Third Reich in Germany that perpetrated the holocaust. The medical community has kept evolving and introducing new moral values and principles while using such egregious events as lessons, ultimately resulting in the Declaration of Helsinki in 1964. This article revisits the heterogeneous journey of integrating humanistic values in anatomy practice. Such humanistic traits that, like medical science, have also developed over centuries through the inputs of physicians, researchers, and philosophers—from Greece to modernity with an important stopgap at the Renaissance—are a fascinating lore that deserves to be re‐envisioned through the lens of contemporary values and ethos. In parallel to human medicine, humanistic values continue to influence veterinary medicine, a welcome development, as our society condemns animal cruelty in any form. There are lessons to be learned from this historical journey of how humanism shaped many of the concepts that anatomists use now. Finally, and most importantly, it might prevent the medical community from repeating the same mistakes by cautioning against the traps that are there, and in a convoluted world where morality as such is eroding from our social fabric, will always be there. Such historical account acts as a righteous, ethical, and contextual compass to guide the existing and upcoming anatomists in discerning between light and dark, right and wrong, and roads—to be or not to be—taken. [ABSTRACT FROM AUTHOR]

Background Informed consent (IC) is essential in defending the autonomy of potential participants in clinical research. Despite the advances in research ethics, particularly in IC, the different guidelines and codes have not been fully implemented. Several studies have presented consent deficiencies that have resulted in unethical practices or poor understanding of the IC. Main body This article reviews the evolution of IC, from its philosophical origins and initial use in the Ottoman Empire (16th century) to its use in clinical research today. It also presents the vision of the European project i-CONSENT (Grant Agreement number: 741856), whose main purpose is to improve the understanding of ICs in research and identifies the key components of a new paradigm to develop patient-centred ICs. Conclusions In many cases, the IC has served to protect the investigator or sponsor from complaints. Different ethical guidelines have sought to make the IC a more useful tool, with little success. Today’s IC is mainly a bureaucratic and legal process that fails to consider the patient’s point of view. In this context, the Guidelines for Tailoring the Informed Consent Process in Clinical Studies provide alternatives to the current IC process, focusing on the patient’s opinions and making them part of the process, thereby improving clinical research quality.

The World Medical Association’s Declaration of Helsinki is in the process of being revised. The following amendments are recommended to be incorporated in pursuit of the common goal of promoting health for all. 1. Data-driven research that facilitates broad informed consent and dynamic consent, assuring participant’s rights, and the sharing of individual participant data (IPD) and research results to promote open science and generate social value. 2. Risk minimisation in a placebo-controlled study and post-trial access to the best-proven interventions for all who need them. 3. A future-oriented research framework for co-creation with all the relevant stakeholders.

Photo by AbsolutVision on Unsplash INTRODUCTION Social media, news headlines, and podcasts implicitly and explicitly remind us of the digital misinformation maelstrom we navigate every day to understand the truth of current events. Misinformation feeds off the topics that impact our lives and draw our attention – war, health, politics, identity, fear, and empathy. Misinformation has a digital reach faster and wider than true information based on its nature of novelty and emotional instigation.[1] It draws from data leakages, twists the truth, incites emotional responses, and can undermine real efforts to protect and aid vulnerable communities. Many of the places and events targeted by misinformation are sites of humanitarian crises such as Gaza, Yamen, and Ukraine among many others. Humanitarian groups conceived to provide relief to vulnerable communities are susceptible to personal harm and impeded aid because the organizational structure is not equipped for misinformation and data security breaches. While propaganda and misinformation did not emerge in the contemporary, their scope, speed, and impact have exponentially increased as the world’s use of digital media for communication developed. The current state of misinformation and data leakages are threats to humanitarian efforts, especially the vital and nuanced task of humanitarian medical aid that now simultaneously relies on the digital information ecosystem. ANALYSIS Humanitarian efforts center on the four main principles of humanity, neutrality, impartiality, and operational independence. The United Nations Refugee Agency specifies that ‘humanity’ refers to addressing human suffering wherever it is found to ensure health and respect, ‘neutrality’ is to not engage in political, racial, religious, or ideological controversies, ‘impartiality’ is to provide aid based on need alone without bias and priority, and ‘operational independence’ is to conduct aid autonomous from agendas or actors in sectors such as political, economic, or military.[2] Medecins Sans Frontieres explicitly states neutrality, impartiality, independence, bearing witness, and accountability in their code of principles. Their statement on medical ethics is much more vague. It aims to “carry out our work with respect for the rules of medical ethics, in particular the duty to provide care without causing harm to individuals or groups. We respect patients’ autonomy, patient confidentiality, and their right to informed consent.”[3] Confidentiality is mentioned, but in the nondescript sense that could refer to confidentiality outlined in any number of medical ethics contexts. Three most commonly referred to ethical codes in Western medicine are the Declaration of Helsinki, the Belmont Report, and the Code of the American Medical Association (AMA). The Declaration of Helsinki places confidentiality in the context of research and was written pre-digital age in the 1960s.[4] The Belmont Report does not mention confidentiality or patient privacy in its summation of medical ethics from 1978.[5] Lastly, the AMA’s Code of Medical Principles upholds that physicians “shall respect the rights of patients, colleagues, and other health professionals, and shall safeguard patient confidences and privacy within the constraints of the law.”[6] This AMA principle was adopted in 1957 and revised in 2001, still before the onset of widely accessible digital media. These three medical ethics codes are the standard of Western medicine, and yet they are decades obsolete when facing the harm of digital misinformation and data leakages. Humanitarian aid organizations cannot afford to rely on outdated medical ethical codes amid digital misinformation and data leakages. Medical humanitarian relief groups such as Medecins Sans Frontiers, the International Medical Corps, the WHO Global Health and Peace Initiative, and the International Committee of the Red Cross, rely on the medical ethics defined in the aforementioned guides in addition to their humanitarian foundation. These codes, while useful, were written prior to the digital age. And, as our methods of communication, medical delivery, and global action have evolved and digitized, the ethics guiding medical practice should be updated to reflect this dramatic change. Humanitarian medical organizations need the digital ecosystem to store metadata for medical services such as patient history, blood type, metrics on locations in need of aid, missing person searches, and funding. The levels of data vulnerable to misconstruction and hacking exist on the personal and organizational levels. Individual providers and the organizational body should prioritize confidentiality. Thus humanitarian medical ethics should adapt to the reality of the digital age to not endanger the populations receiving aid and to not propagate harm. Misinformation and data leakage can lead to microtargeting, defamation, provider endangerment, and other harms preventing medical service. The European Data Protection Supervisor details how the personal information collected by organizations, such as medical, can be stolen or misconstrued to affect microtargeting, placing individuals in the direct path of echo chambers, digital tracking, and manipulation.[7] The International Broadcasting Trust released a report in 2018 detailing the extent to which misinformation was impacting the humanitarian aid groups it broadcasts to.[8] For example, the report shared that rumors spread by right-wing political groups in 2017 falsely circulated that humanitarian groups in the Mediterranean were collaborating with child trafficking rings.[9] After causing defamation, the right-wing group sent a boat to block and detain the humanitarian group’s search and rescue boat. This was one incident among many where providers and patients were put in harm’s way through misinformation and the misuse of location data. Other disinformation campaigns can be carried out by governments as well; in Syria and Ukraine, the Russian government has been specifically targeting Red ross and White Helmets.[10] Beneficial medical services cannot be delivered if providers and patients are targeted. In January of 2022, the International Association of the Red Cross was hacked. Approximately 515,000 vulnerable persons’ data was leaked and became inaccessible to the IARC providers.[11] If an organization cannot protect access to its digital ecosystem, humanitarian medical aid efforts can be rendered ineffective. Additionally, misinformation and breached data cause the less immediate but more widely impactful harm of distrust. Stakeholders and funding sources can withdraw from supporting medical humanitarian aid organizations. Beneficial medical services cannot be offered if there is no monetary backing. Providers and patients also have their own digital devices and means of communication which can lead to sensitive information being shared online or with non-neutral parties. If a patient cannot trust their provider or the organization a provider acts in the name of, medical services can be refused. Beneficial medical service cannot be conducted if the trust of the patient is compromised by humanitarian groups failing to prioritize patient confidentiality. Confidentiality should be prioritized in humanitarian medical aid to safeguard against the extended harms of data leakage, misinformation, and malintent. Some critiques may postulate that due to the uniqueness of each community aided by medical humanitarian organizations, over-standardization from rigid ethical codes may occur, that standardization can lead to inflexibility with communities and render aid strategies ineffective. However, the reality is that ethical frameworks make sure that individual actors are not monolithic – they allow for collaboration and joint work. The WHO Global Health and Peace Initiative’s recent adoption of conflict sensitivity, along with other organizations’ additions of similar language, ensure that there is a feedback loop incorporated into the ethical code to mitigate unintended harm. Thus, ethical codes are helping providers to respond in unprecedented situations with consciousness to harm propagation. In events of limited time and of crisis, comprehensive ethical codes are especially beneficial because we rely on habits and pre-established information banks. CONCLUSION Humanitarian medical ethics should include a specific guide for confidentiality. Without forethought and the integration of traditional and digital confidentiality as a main tenant, medical humanitarian organizations will continue to act retrospectively. Trust in stakeholder-provider-patient relationships will continue to disintegrate. The current status quo of medical ethics in the humanitarian aid sector poses multiple risks for providers and patients whereas adopting stronger confidentiality language is a tangible step towards the protection of vulnerable communities from the harms of digital misinformation and data leakage. - [1] Vosoughi, Soroush, Deb Roy, and Sinan Aral. “The Spread of True and False News Online.” Science 359, no. 6380 (2018): 1146–51. https://doi.org/10.1126/science.aap9559. [2] “Conflict Sensitivity and the Centrality of Protection.” The Global Portection Cluster , March 2022. https://www.globalprotectioncluster.org/sites/default/files/2023-03/220318_gpc_-_conflict_sens.pdf. [3] “Our Charter and Principles.” MEDECINS SANS FRONTIERES - MIDDLE EAST. Accessed December 24, 2023. https://www.msf-me.org/about-us/principles/our-charter-and-principles#:~:text=We%20give%20priority%20to%20those,of%20governments%20or%20warring%20parties.&text=The%20principles%20of%20impartiality%20and%20neutrality%20are%20not%20synonymous%20with%20silence. [4] “WMA - The World Medical Association-WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects.” The World Medical Association. Accessed December 24, 2023. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. [5] Office for Human Research Protections (OHRP). “ The Belmont Report.” United States Department of Health and Human Services , September 27, 2022. https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html. [6] American Medical Association . “The Code .” AMA principles of Medical Ethics. Accessed December 24, 2023. https://code-medical-ethics.ama-assn.org/principles. [7] “EDPS Opinion on Online Manipulation and Personal Data .” European Data Protection Supervisor. Accessed December 24, 2023. https://edps.europa.eu/sites/edp/files/publication/18-03-19_online_manipulation_en.pdf. [8] Robin. “Faking It: Fake News and How It Impacts on the Charity Sector.” International Broadcasting Trust, March 13, 2020. https://www.ibt.org.uk/reports/faking-it/. [9] Reed, B. “Charities Colluding with Traffickers? Fake News.” The Guardian, February 15, 2018. https://www.theguardian.com/global-development/2018/feb/15/charities-aid-agencies-fake-news-says-report. [10] Sant, Shannon Van. “Russian Propaganda Is Targeting Aid Workers.” Foreign Policy, August 1, 2022. https://foreignpolicy.com/2022/08/01/russia-disinformation-ukraine-syria-humanitarian-aid-workers/ . [11] International Committee of the Red Cross. “Hacking the Data of the World’s Most Vulnerable Is an Outrage.” International Committee of the Red Cross, October 27, 2022. https://www.icrc.org/en/document/hacking-data-outrage.

Abstract Aim To determine the level of evidence for innovative high-risk medical devices at market entry. Methods We reviewed all Belgian healthcare payer (RIZIV-INAMI) assessor reports on novel implants or invasive medical devices (n = 18, Class IIb-III) available between 2018 to mid-2019 on applications submitted for inclusion on their reimbursement list. We also conducted a review of the literature on evidence gaps and an analysis of relevant legal and ethical frameworks within the European context. Findings Conformity assessment of medical devices is based on performance, safety, and an acceptable risk-benefit balance. Information submitted for obtaining CE marking is confidential and legally protected, limiting access to clinical evidence. Seven out of the 18 RIZIV-INAMI assessor reports (39%) included a randomized controlled trial (RCT) using the novel device, whilst 2 applications (11%) referred to an RCT that used a different device. The population included was inappropriate or unclear for 3 devices (17%). Only half of the applications presented evidence on quality of life or functioning and 2 (11%) presented overall survival data. Four applications (22%) included no data beyond twelve months. The findings from the literature demonstrated similar problems with the study design and the clinical evidence. Discussion and conclusions CE marking does not indicate that a device is effective, only that it complies with the law. The lack of transparency hampers evidence-based decision making. Despite greater emphasis on clinical benefit for the patient, the provisions of the European Medical Device Regulation (MDR) are not yet fully aligned with international ethical standards for clinical research. The MDR fails to address key issues, such as the lack of access to data submitted for CE marking and a failure to require evidence of clinical effectiveness. Indeed, a first report shows no improvement in the clinical evidence for implantable devices generated under the MDR. Thus, patients may continue to be exposed to ineffective or unsafe novel devices. The Health Technology Assessment Regulation plans for Joint Scientific Consultations for specific high-risk devices before companies begin their pivotal clinical investigations. The demanded comparative evidence should facilitate payer decisions. Nevertheless, there is also a need for legislation requiring comparative RCTs assessing patient-relevant outcomes for high-risk devices to ensure implementation, including development and implementation of common specifications for study designs.

Patient safety in surgical settings is an integral part of the further sustainable development of medicine in Ukraine. This is key in times of the war and post-war state when the budget deficit at all levels of public administration and health care is significant and may grow significantly in the future. Medical errors during anesthetic management and surgery are particularly costly and significantly burden the health care system. Even the wealthiest economies cannot afford such mistakes. The price is particularly high for Ukrainian realities, and these mistakes are fatal for our health care. For this review, the authors used the electronic databases MEDLINE and Embase. 15 studies were included in the review. A part of the data was also included from the department research. Demonstration of own results is limited, as the data have already been published in other publications or materials are in the reviewing process. Basic monitoring according to the WHO standards / World Federation of Societies of Anesthesiologists (WFSA) is mainly used in hospitals of European Union countries. Results are close to 100 % for pulseoximetry and blood pressure, 98 % for electrocardiography, and 96 % for capnography. In Ukraine, monitoring methods do not have critical differences, except for a slightly lower (73.7 %) spread of capnography and ECG monitoring (83.4 %). The situation is less encouraging in the context of regional anesthesia. In Ukraine, the situation is much worse. According to the survey conducted by our department, ultrasound navigation is available in only 67 % of hospitals. There is also a low level of taking safety measures, which include checklists, training, and clinical analyzes of errors. Conclusions. According to the data of this literature review, the components of the Declaration of Helsinki on safety in anesthesiology are gradually being implemented in Ukraine, the use of the WHO checklist "Safe surgery" and safety standards of regional anesthesia is spreading. The main directions for further development are the education of physicians and other staff on patient safety, the approval of national standards and monitoring of their implementation in practice, the creation of a notification and audit system for complications and critical incidents during anesthesia. [ABSTRACT FROM AUTHOR]

Recent technological developments have considerably transformed the supply, storage, and transportation processes of cadavers, creating new and previously unforeseen ethical challenges regarding cadaver usage. In this study, we analyzed two aspects of the cadaver processing system—cadaver supply and its use in research. Thereafter, we highlighted the major ethical concerns underlying these stages and correlated our search results with the ethical principles outlined in the Declaration of Helsinki (DoH), or Helsinki Declaration. To ensure the reliability and continuity of medical progress, human—especially cadaver—research depends on the ethical priorities as outlined in the DoH: respect for autonomy, privacy/confidentiality, risks/burdens/benefits, and the protection of vulnerable groups. According to our ethics analysis, which also corresponds with the ethics guidelines of the Consensus Panel on Research with the Recently Dead, the most ignored values were respect for autonomy and privacy/confidentiality issues. Based on these ethical concerns, we provide recommendations to address these challenges in anatomy research. [ABSTRACT FROM AUTHOR]

Aim: To determine the level of evidence for innovative high-risk medical devices at market entry. Methods: We reviewed all Belgian healthcare payer (RIZIV-INAMI) assessor reports on novel implants or invasive medical devices (n = 18, Class IIb-III) available between 2018 to mid-2019 on applications submitted for inclusion on their reimbursement list. We also conducted a review of the literature on evidence gaps and an analysis of relevant legal and ethical frameworks within the European context. Findings: Conformity assessment of medical devices is based on performance, safety, and an acceptable risk-benefit balance. Information submitted for obtaining CE marking is confidential and legally protected, limiting access to clinical evidence. Seven out of the 18 RIZIV-INAMI assessor reports (39%) included a randomized controlled trial (RCT) using the novel device, whilst 2 applications (11%) referred to an RCT that used a different device. The population included was inappropriate or unclear for 3 devices (17%). Only half of the applications presented evidence on quality of life or functioning and 2 (11%) presented overall survival data. Four applications (22%) included no data beyond twelve months. The findings from the literature demonstrated similar problems with the study design and the clinical evidence. Discussion and conclusions: CE marking does not indicate that a device is effective, only that it complies with the law. The lack of transparency hampers evidence-based decision making. Despite greater emphasis on clinical benefit for the patient, the provisions of the European Medical Device Regulation (MDR) are not yet fully aligned with international ethical standards for clinical research. The MDR fails to address key issues, such as the lack of access to data submitted for CE marking and a failure to require evidence of clinical effectiveness. Indeed, a first report shows no improvement in the clinical evidence for implantable devices generated under the MDR. Thus, patients may continue to be exposed to ineffective or unsafe novel devices. The Health Technology Assessment Regulation plans for Joint Scientific Consultations for specific high-risk devices before companies begin their pivotal clinical investigations. The demanded comparative evidence should facilitate payer decisions. Nevertheless, there is also a need for legislation requiring comparative RCTs assessing patient-relevant outcomes for high-risk devices to ensure implementation, including development and implementation of common specifications for study designs. [ABSTRACT FROM AUTHOR]

The article reports that the World Medical Association started revisions to the Declaration of Helsinki in 2022 and it address numerous issues that have arisen in research ethics since the last 2013 revision. Topics include examines in the face of critical issues that have surfaced during the COVID-19 pandemic, less salient but nevertheless critically important issues may go unnoticed.

BackgroundThe creation of the legal framework to recognize rights of patients and participants in clinical trials began in Germany in the 19th century. However, the ethical review of medical research in terms of the protection of rights and welfare of human subjects has only become a widespread practice since the establishment of ethics commissions. The first ethics commissions emerged at the universities under the influence of the German Research Foundation. The widespread establishment of ethics commissions began in the Federal Republic of Germany in 1979, after the adoption of the recommendation of the German Medical Association for the establishment of ethics commissions.Materials and methodsWe analyzed unpublished archival documentation of the Ethics Commission of the University of Ulm and evaluated it based on a thorough review of research works on the history of international and German ethics commissions. For the examination of the sources, we implemented the historical-critical method.ResultsThe first ethics commission in Germany was set up at the University of Ulm in 1971/72. The reason for that was that the German Research Foundation required grant applications for medical research involving human subjects to be reviewed by an ethics commission. Initially the commission was created at the Center for Internal Medicine and Pediatrics, its authority grew over time until in 1995 it became the central Ethics Commission for the entire University of Ulm. Before the adoption of the Tokyo revision of the Declaration of Helsinki in 1975, the Ulm Ethics Commission developed its own guidelines for the conduct of scientific investigations on humans based on international ethical principles.ConclusionThe Ethics Commission of the University of Ulm must have been established between July 1971 and February 1972. The German Research Foundation played a decisive role in the establishment of the first ethics commissions in Germany. The Universities had to create ethics commissions in order to be able to obtain additional funds from the Foundation for their research. Thus, the Foundation initiated the institutionalization of the ethics commissions in the early 1970s. The functions and composition of the Ulm Ethics Commission were similar to other initial ethics commissions of the time.

During recent years, the burden of bureaucracy in clinical research has increased dramatically, adversely impacting the activity of investigators and clinical research teams. Although compliance with the Declaration of Helsinki, the guidelines for Good Clinical Practice (GCP), and other applicable regulations remains unquestionable, their overinterpretation and substitution by the internal operating procedures of sponsors and Contract Research Organizations (CROs) have increased the administrative burden. A survey conducted by the European Society for Medical Oncology (ESMO) Clinical Research Observatory (ECRO) among 940 investigators confirmed that they considered that the administrative burden in clinical research is excessive; that administrative procedures could be reduced without affecting the safety and the rights of the patients and the quality of the data; and that bureaucracy represents an obstacle for clinical research. A panel of physicians with extensive experience in clinical research, composed by members of the ECRO and the ESMO Scientific Medical and Public Policy divisions, analyzed clinical trial procedures related to administrative workflow, pharmacovigilance, and medical care. The panel identified situations that generate debate between investigators and sponsors/CROs and selected real clinical scenarios that exemplify such situations. The panel discussed and proposed specific recommendations for those situations, based on GCP. This initiative aspires to streamline clinical research procedures and to become a platform for discussion among all clinical trial stakeholders, with the aim of promoting the sustainability of clinical research and the care of cancer patients. • The burden of bureaucracy in clinical research is overwhelming investigators and clinical research teams. • This ESMO manuscript proposes a framework of principles to improve sponsoring and monitoring of clinical trials. • We expect this awareness call to streamline clinical research and to promote the welfare of patients. [ABSTRACT FROM AUTHOR]

The Declaration of Helsinki (DoH), the International Committee of Medical Journal Editors (ICMJE) recommendations, and the Committee on Publication Ethics (COPE) guidelines outline the basic principles for ethical conduct and publication of human-subject research, most notably informed consent (IC) and research ethics committee (REC) approval. This retrospective observational study was a first study to investigate the quality of reporting of these protections in a selected sample of medical papers published in Turkey. A total of 573 research articles published in the official journals of six leading Turkish medical schools between January 2018 and December 2020 were searched for information on obtaining (i) REC approval, (ii) written IC from research subjects or their legal guardians/representatives, and (iii) an REC-granted IC waiver when it was found, as stated in the DoH, "impossible or impracticable to obtain consent" from research subjects. Similarly, a total of 166 case reports were searched for a statement about publication-specific IC, as was recommended by COPE. Despite a statistically significant improvement over the years, the overall rates were found to be unsatisfactory. The protections were particularly misused or underused in retrospective research, where the rates of reporting written IC (15.41% vs. 48.61%) and REC approval with date and reference number information (45.38% vs. 61.11%) were significantly lower than in prospective research (p <.05). Both the practices of seeking and granting an IC waiver when no IC was obtained were extremely rare (n = 3). It was also found that the requirement of structured ethical information in research papers was associated with higher levels of ethics compliance, and that medical publishing in Turkey needed specific improvements, including better implementation of the protections already adopted in principle, clearer instructions for authors, more rigorous editorial scrutiny, and greater commitment to rejecting substandard submissions. [ABSTRACT FROM AUTHOR]

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Our study describes the reported rate of the Institutional Review Board (IRB) approval, declaration of Helsinki (DoH), and informed consent in the case reports and case series and investigates factors associated with the ethical approval report. We searched PubMed for case reports and case series from 2006 to 2017. Annually, we obtained the first 20 articles of a case report cluster from 20 distinct publications. This analysis initially contained at least 2400 papers, with 100 papers each study design and year. Only 26 (5.4%) of 480 included studies reported IRB approval, DoH approval, and participant informed consent; 58 (12.1%) reported two out of three ethical statements (DoH, informed consent, IRB); and 151 (31.5%) reported only one, leading to nearly 245 studies (51.0%) did not report any ethical approval item. Both clusters mentioned the DoH the least. Only years, ages, ethical item types, and cluster types were associated with ethical reporting practices. This study found the serious under-reporting of ethical practices in both case reports and case series., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Care Science published by John Wiley & Sons Ltd on behalf of Tsinghua University Press.)

The vulnerability of research participants is a critical topic for the 2024 revision of the Declaration of Helsinki, with the proposal to include "social value. " However, this proposal has been withdrawn and the relationship between the two concepts has not been clarified. This paper attempts to clarify: (1) the recent reform for the ethical inclusion of vulnerable study participants to promote diversity; (2) the social value, prerequisite for everyone, especially for those who are vulnerable and the most in need; (3) the requirements for promoting the inclusion of vulnerable participants, in particular the review of the norms for placebo-controlled trials and post-trial access; (4) finally, the direction of research ethics reform to achieve social value and equitable global health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kurihara, Greco, Dhai, Matsuyama and Baroutsou.)

This paper examines the arguments used to claim that we should use nonhuman animals in research, rather than methods that do not involve animals, while we should reject human experimentation. The paper argues that the appeal to an axiological or a normative gap between the weight of the interests of humans and nonhuman animals has several unacceptable implications. It then points at a battery of problematic consequences that other anthropocentric positions have. Finally, the paper argues that even if anthropocentrism is correct, the aggregate weight of animals' interests may prevail over that of human interest in using them. [ABSTRACT FROM AUTHOR]

Abstract Background Importance of awareness of medical ethics and its integration into medical curriculum has been frequently highlighted. Study 1 aimed to assess the knowledge, attitude, and reported practices of medical ethics among clinicians at Patan Academy of Health Sciences, a tertiary care teaching hospital in Nepal. Study 2 was conducted to assess whether there was a difference in knowledge, attitude, and reported practices of medical ethics among doctors who received formal medical ethics education during undergraduate studies and those who did not. Methods Two cross-sectional surveys using self-administered questionnaires were conducted. Study 1 included 72 participants; interns, medical officers, and consultants working at Patan Academy of Health Sciences. Study 2 was a comparative study conducted among 54 medical officers who had received formal medical ethics education (Group 1) and 60 medical officers who did not (Group 2). Results Participants who had completed post-graduate education had higher knowledge (p = 0.050), practice (p

Photo by Diana Polekhina on Unsplash ABSTRACT Randomized placebo-controlled trials are often used in clinical research, though there are ethical concerns regarding their use. The Food and Drug Administration (FDA) has rejected international stances on placebo-controlled trial use in favor of the bioethical principles of autonomy, beneficence, nonmaleficence, and justice. The FDA permits placebo-controlled trials in three circumstances: when there are no established treatments available when their use would be of negligible harm to the patient, and when there are compelling reasons for their use. However, in some cases, the FDA’s approval of placebo-controlled trials violates bioethical principles. Ultimately, the FDA should overhaul its practices regarding the use of placebo-controlled trials. INTRODUCTION Randomized placebo-controlled clinical trials (PCTs) are considered the most rigorous method of understanding the efficacy of an intervention and, as a result, are widely used in clinical research.[1] However, there are ethical concerns regarding placebo controls, including their use in the study of deadly diseases or when effective treatments already exist, though poor oversight and lax rules have largely permitted PCT research, even under those conditions.[2] The FDA prefers PCTs for most interventional research and considers them essential to test the efficacy of drugs. Between 2006-2011, 40 percent of FDA-approved clinical trials used a placebo alone for comparison. The FDA has been lagging in altering its policies regarding PCTs, only advising against PCT research in select oncological cases for the first time in 2019 in a nonbinding guidance. It is our belief that the FDA should change its approach and prohibit the use of placebo controls in clinical trials where effective treatments already exist. l. Brief History of PCTs and the FDA In contemporary research practices, PCTs are used to evaluate whether an intervention is effective by comparing it to a control group that received a treatment designed to have no real effect (placebo). Throughout the 20th century there have been numerous bioethical tragedies, including but not limited to the Holocaust and the Tuskegee Syphilis Study.[3] These and other transgressions have become an impetus for establishing ethical research standards preventing human exploitation in the name of science. The Declaration of Helsinki, adopted in 1964, a nonbinding instrument, restricts the use of PCTs. Clause 33 of the Declaration of Helsinki states that new medical interventions should be tested against previously demonstrated interventions and placebos should be used only if there is no existing intervention with narrow exceptions. Clause 33 says the effectiveness of a new intervention must be tested against those of the best current proven intervention (s), except in the following circumstances: Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or Where for compelling and scientifically sound methodological reasons the use of any intervention less effective than the best proven one, the use of placebo, or no intervention is necessary to determine the efficacy or safety of an intervention and the patients who receive any intervention less effective than the best proven one, placebo, or no intervention will not be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention. Extreme care must be taken to avoid abuse of this option.[4] The FDA has largely ignored this and deemed placebo controls the gold standard, stating that “PCTs are necessary to control for placebo effect of investigational medicinal product.”[5] The FDA has even refused to approve drugs that are tested against established treatments instead of against placebos, notably atenolol.[6] By stretching the “methodological” exception and failing to define harm reasonably, the FDA does not meet the spirit behind Helsinki’s conditions for allowing PCTs. When the Declaration of Helsinki was revised in 2000 to increase restrictions, the Director of Medical Policy for the FDA’s Center for Drug Evaluation and Research considered it “unpardonable” and abandoned any compliance with it in 2008.[7] The FDA’s past statements and actions have supported its belief that drug approval hinges on the use of placebos. While the FDA has rejected the Declaration of Helsinki’s stance on placebos, it has remained faithful to the guidelines of other bioethical codes such as the International Ethical Guidelines for Biomedical Research Involving Human Subjects and the Council for International Organization of Medical Science’s guidelines for biomedical research involving human subjects. The International Ethical Guidelines for Biomedical Research Involving Human Subjects permits PCTs if the consequences are negligible, when methodologically advantageous, and when responses have been historically erratic.[8] The Council for International Organization of Medical Science’s guidelines for biomedical research involving human subjects echoed the Declaration of Helsinki in guideline 11, stating that a “‘placebo may be used: When there is no effective intervention; when withholding an established, effective intervention would expose to, at most temporary discomfort, or delay in relief symptoms; when use of an established, effective intervention as comparator would not yield scientifically reliable results and the use of the placebo would not add risk of serious or irreversible harm to subjects.”[9] The Belmont Report notes three ethical principles: beneficence, respect for persons (autonomy), and justice. The Common Rule requires IRBs for human research and reflects principles noted in the Belmont Report. The Belmont Report covers three applications of its principles: Informed consent, selection of research subjects, and risk-benefit assessments.[10] In 1979, Beauchamp and Childress established the four principles approach to bioethics including autonomy, beneficence, nonmaleficence, and justice. While PCTs were not mentioned in these reports, the principles in them permit placebo controls as long as subjects are informed of the risks of participating and risks are minimized. The FDA has since followed that approach. These guidelines have made PCTs ethically ambiguous, and there are moral counterpoints to be made. ll. FDA-PCT Conditions The FDA has permitted PCT use under three conditions. The first condition is when there is no proven intervention for the medical condition under the study. This means treatment has either not been found for a disease or has not yet been translated into clinical practice and is not controversial. The second condition is when there is negligible harm to the patient from delaying or forgoing an available treatment. In this scenario, a placebo is not suspected to cause damage and the available treatment is meant for mild conditions that pose low-risk adverse effects, which is said to justify its use. The final condition is when there are compelling methodologic reasons for the use of the placebo. This scenario is for situations where outcomes fluctuate for complex reasons making other research methods likely to be unreliable. This condition for PCT use is also justified when it is not possible to administer the intervention to the experimental group because of economic, social, or administrative factors, in which case it is believed to be better to have results of some kind than none at all.[11] We will argue each condition is unethical to the current degree it is practiced. lll. Condition One: Lack of Established Treatment Placebo use in cases where no established treatment exists would not typically be considered unethical. However, placebos continue to be used in numerous clinical trials approved by the FDA, many of which already have standard interventions.[12] In addition, the lack of head-to-head drug trials, in favor of placebo, has had no benefit on clinical guidelines and practices. The direct comparison of drugs in head-to-head trials gives physicians and buyers a better understanding of the effectiveness of a drug and allows for the creation of more robust clinical guidelines. Instead, under the PCT model, the market is saturated with a plethora of drugs to choose from. While each one may be better than placebo, it can be difficult to understand how each treatment compares to another, which may be harmful to patients. A recent study has shown that nearly 90 percent of new drugs do not perform better than existing options.[13] There is an ethical cost to be considered when devoting financial resources and effort to create new drugs that are inferior to existing treatments and have not led to changes to clinical practice. While the FDA claims to follow the bioethical principles of beneficence and nonmaleficence, its choice of approving treatments through placebo controls, despite the existence of standard interventions, counters these guidelines. lV. Condition Two: Negligible Harm from Delayed Treatment The International Ethical Guidelines for Biomedical Research Involving Human Subjects argues that placebos are acceptable if there is only “temporary discomfort or a delay in relief of symptoms,” a stipulation that the FDA follows. However, what constitutes temporary is arbitrary, as there is no absolute reference of time prescribed, nor is there a defined proportion relative to total life expectancy available. For example, many patients in trials for terminal illnesses have a limited therapeutic window and a reduced life expectancy, so they value time differently from someone with a non-terminal illness. Additionally, there is no consensus of what constitutes harm when withholding treatment; placebos are often used in trials for major depressive disorder, yet this population has statistically higher rates of self-harm and suicide without treatment compared to the general population.[14] Serious risks can be incurred due to a placebo intervention by not offering experimental treatment, without excusing the psychological harm withholding a treatment may have on a patient should it be unblinded. Nevertheless, the FDA has used the umbrella term of “temporary discomfort” to justify the widespread use of PCTs, but the vagueness of this language results in human suffering. V. Condition Three: Compelling Methodological Reasoning Finally, the FDA authorizes placebo use in cases where for compelling scientifically sound methodological reasons, the use of placebo is necessary to determine the efficacy or safety of an intervention, and the parties who receive placebo or no treatment will not be subject to any risk of serious or irreversible harm. The condition includes cases where PCT is believed to be necessary to demonstrate efficacy, such as in trials of psychoactive drugs where evidence is inconsistent due to disease heterogeneity and demonstrating equivalence to an established treatment is insufficient. There are also arguments that PCTs, while not necessary, may be beneficial in generating socially valuable knowledge. However, whether a placebo control demonstrates efficacy is not sufficient to justify its use. When considering the ethical use of PCTs, investigators must weigh the social value gained against the risks of no treatment in the control. Unfortunately, the risk-benefit analysis is often controversial. For example, in 2001, the FDA initially responded positively to a placebo-controlled trial of Surfaxin in infants with acute respiratory distress syndrome in Latin America. However, the trial was deemed exploitative by a public watch group when it was revealed that the drug was already FDA-approved in the United States, and the manufacturer of that drug was undertaking another study with the same drug in Europe without any placebos. To justify withholding treatment from a vulnerable population in a developing country, the manufacturer stated that they would be providing a drug that would otherwise be unavailable to many participants, and the risks would be compensated by upgrades to the host country’s medical infrastructure. Despite the FDA’s initial approval and the manufacturer’s attempt to quell public outcry, objections by the public led to the removal of the placebo arm from the trial. While the FDA believes there may be methodologically compelling reasons to utilize PCTs, they have demonstrated a lack of judgment necessary to balance the gains against their inherent losses, requiring the public to step in. CONCLUSION Based on the ambiguous bioethical guidelines that the FDA follows, and the moral justifications described in this paper, its preference of PCTs is unethical. We suspect the overreliance of PCTs has resulted in harm to research participants and the general population, which is why the FDA should change its policy. We propose that PCTs be used only for diseases that lack an established treatment, as decreed by Clause 33 of the Declaration of Helsinki. Other measures that would satisfy Clause 33, the Belmont Report, and the Common Rule are the use of large retrospective observational trials for comparison rather than a prospective placebo group. Ultimately, it is ethically necessary that the FDA modify its practices regarding drug approval and more stringently scrutinize PCTs as well as adopt more favorable approaches to other comparative models. Acknowledgments We sincerely thank Dr. Gregory James Smith, JD, DBE for his patience and guidance in both the research and writing of this paper. - [1] Simmonds A. Ethics of placebo-controlled trials in developing countries: The Search for Standards and Solutions. The Morningside Review. https://journals.library.columbia.edu/index.php/TMR/article/view/5507. Published May 1, 2011. Accessed April 21, 2022; Millum J, Grady C. The ethics of placebo-controlled trials: Methodological Justifications. Contemporary Clinical Trials. 2013;36(2):510-514. doi:10.1016/j.cct.2013.09.003; Center for Drug Evaluation and Research. Institutional Review Boards (IRBs) and Protection of Human Subjects in Clinical Trials. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/institutional-review-boards-irbs-and-protection-human-subjects-clinical-trials. Published September 11, 2019. Accessed April 21, 2022. [2] Keränen T, Halkoaho A, Itkonen E, Pietilä A-M. Placebo-controlled clinical trials: How trial documents justify the use of randomisation and Placebo. BMC Medical Ethics. 2015;16(1). doi:10.1186/1472-6939-16-2; Feifel D. The use of placebo-controlled clinical trials for the approval of psychiatric drugs: part I-statistics and the case for the "greater good.” Psychiatry (Edgmont). 2009;6(3):41-43; van der Graaf R, Rid A. Placebo-controlled trials, ethics of. International Encyclopedia of the Social & Behavioral Sciences. 2015:164-173. doi:10.1016/b978-0-08-097086-8.11011-6; Ibrahim MS, Ovosi JO, Bello-Ovosi BO. Randomized controlled trials: Ethical and scientific issues in the choice of placebo or active control. Annals of African Medicine. 2017;16(3):97-100. doi:10.4103/aam.aam_211_16; Sorscher S, AbuDagga A, Almashat S, Carome M, Wolfe S. Placebo-only-controlled versus active-controlled trials of new drugs for nine common life-threatening diseases. Open Access Journal of Clinical Trials. 2018;Volume 10:19-28. doi:10.2147/oajct.s156054; Mezher M. FDA finalizes guidance on placebos and blinding for cancer trials. Regulatory Affairs Professionals Society (RAPS). http://www.raps.org/news-and-articles/news-articles/2019/8/fda-finalizes-guidance-on-placebos-and-blinding-fo. Published August 28, 2019. Accessed April 21, 2022. [3] WMA Declaration of Helsinki – ethical principles for medical research involving human subjects. The World Medical Association. http://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. Published July 9, 2018. Accessed April 21, 2022. [4] WMA Declaration of Helsinki, Clause 33. [5] Ovosi JO, Ibrahim MS, Bello-Ovosi BO. Randomized controlled trials: Ethical and scientific issues in the choice of placebo or active control. Ann Afr Med. 2017;16(3):97-100. doi:10.4103/aam.aam_211_16; Rothman KJ, Michels KB. The continuing unethical use of placebo controls. New England Journal of Medicine. 1994;331(6):394-398. doi:10.1056/nejm199408113310611 [6] Rothman KJ, Michels KB. The Continuing Unethical Use of Placebo Controls. New England Journal of Medicine.1994;331(6):394-98. doi:10.1056/nejm199408113310611 [7] Hollon T. FDA uneasy about placebo revision. Nature Medicine. 2001;7(1):7-7. doi:10.1038/83389 [8] International Ethical Guidelines for Biomedical Research Involving Human Subjects. Geneva: CIOMS; 1993. https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf. Accessed April 21, 2022. [9] Ovosi JO, Ibrahim MS, Bello-Ovosi BO. Randomized controlled trials: Ethical and scientific issues in the choice of placebo or active control. Ann Afr Med. 2017;16(3):97-100. doi:10.4103/aam.aam_211_16 [10] The Belmont Report Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, D.C: U.S. Government Print. Off; 1978. Accessed April 21, 2022. Office for Human Research Protections (OHRP); Federal Policy for the Protection of Human Subjects ('Common Rule'). HHS.gov. https://www.hhs.gov/ohrp/regulations-and-policy/regulations/common-rule/index.html. Published June 16, 2021. Accessed April 21, 2022. [11] Millum J, Grady C. The ethics of placebo-controlled trials: Methodological justifications. Contemporary Clinical Trials. 2013;36(2):510-514. doi:10.1016/j.cct.2013.09.003; Center for Drug Evaluation and Research. Institutional Review Boards (IRBs) and Protection of Human Subjects in Clinical Trials. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/institutional-review-boards-irbs-and-protection-human-subjects-clinical-trials. Published September 11, 2019. Accessed April 21, 2022. [12] Center for Drug Evaluation and Research. New drug therapy approvals 2020. U.S. Food and Drug Administration. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2020#first-in-class. Published January 8, 2021. Accessed April 21, 2022. [13] Light DW, Lexchin J, Darrow JJ. Institutional corruption of pharmaceuticals and the myth of safe and effective drugs. Journal of Law, Medicine & Ethics. 2013;41(3):590-600. doi:10.1111/jlme.12068 [14] Lahey T. The ethics of clinical research in low- and middle-income countries. Ethical and Legal Issues in Neurology. 2013:301-313. doi:10.1016/b978-0-444-53501-6.00025-1

The Declaration of Helsinki is a set of ethical principles to be followed by scientists involved in medical research with humans or human cells and tissues. This Declaration defines how scientific research should be planned, carried out, documented, analysed, and published. We summarise and discuss some ethical issues related to publishing original articles, including clinical trials, review papers, and case reports based on the seventh revision of the Declaration of Helsinki. The principles of the Declaration of Helsinki refer most strongly to the publication of medical research results, in particular clinical trials, as original articles. Such papers must meet several ethical requirements, especially the study protocol transparency and the presentation of the results. For case reports, the bioethical aspects related to their publication are twofold - they must include informed and voluntary consent and the confidentiality of study participants. The review papers are of the least bioethical concern. However, whether patients' agreements with specific studies are valid if the data are used in meta-analyses is uncertain. Adherence to ethical policies and standards helps to ensure the highest possible quality of scientific publications. Responsibility for compliance with the Declaration of Helsinki lies not only with the authors preparing their manuscripts but also with the editorial board and reviewers, who must evaluate the ethical soundness of the submitted papers. The additional guidelines for the different types of studies facilitate the implementation of the Declaration principles.

The Declaration of Helsinki is a set of ethical principles to be followed by scientists involved in medical research with humans or human cells and tissues. This Declaration defines how scientific research should be planned, conducted, documented, analysed, and published. We summarise and discuss some ethical issues related to publishing original articles, including clinical trials, review papers, and case reports based on the seventh revision of the Declaration of Helsinki. The principles of the Declaration of Helsinki refer primarily to the publication of medical research results, in particular clinical trials, as original articles. Such papers are required to meet several ethical requirements, particularly the study protocol transparency and the presentation of the results. In terms of case reports, the bioethical aspects related to their publication are twofold - they need to include informed and voluntary consent and the confidentiality of study participants. The review papers are of the least bioethical concern. However, whether patients' agreements with specific studies are valid if the data are used in meta-analyses is uncertain. Adherence to ethical policies and standards helps to ensure the highest possible quality of scientific publications. Responsibility for compliance with the Declaration of Helsinki lies not only with the authors preparing their manuscripts, but also with the editorial board and reviewers, who must evaluate the ethical soundness of the submitted papers. The additional guidelines for the different types of studies facilitate the implementation of the Declaration principles. [ABSTRACT FROM AUTHOR]

This paper targets an orphan topic in research ethics, namely the so called principle of the primacy of the human being, which states that the interests of the human subject should always take precedence over the interests of science and society. Although the principle occupies the central position in the majority of international ethical and legal standards for biomedical research, it has been commented in the literature mainly in passing. With a few notable exceptions, there is little in-depth discussion about the meaning and role of the principle. Several authors note that the principle is vogue, ambiguous and apparently conflicting with the accepted practice of conducting non-beneficial research on individuals unable to give consent. There are opinions that it is just "a vacuous figure of speech" and should be abandoned. This paper argues that the primacy principle is far from being "a vacuous figure of speech", rather it should be seen as a threefold concept: a fundamental interpretative rule, a procedural rule, and a substantive rule aimed at protecting research subjects from instrumental treatment and unacceptable risks. This interpretation tracks back to the principle regulatory and normative origins in the Declaration of Helsinki of 1975, but also acknowledges changes in research ethics and practice, which took place at the turn on the twentieth and twenty-first centuries. Thus, the proposed reading of the principle is not only original, but also historically grounded and normatively fruitful. It provides a fresh and ethically rich perspective on extensively debated, but still controversial problem of an upper limit of permissible risks in non-beneficial studies. [ABSTRACT FROM AUTHOR]

Abstract Background Expanded access is the use of investigational drugs (IDs) outside of clinical trials. Generally it is performed in patients with serious and life-threatening diseases who cannot be treated satisfactorily with authorized drugs. Legal regulations of expanded access to IDs have been introduced among others in the USA, the European Union (EU), Canada and Australia. In addition, in the USA an alternative to expanded access is treatment under the Right-to-Try law. However, the treatment use of IDs is inherently associated with a number of ethically relevant problems. Main text The objective of this article is to present a coherent framework made up of eight requirements which have to be met for any treatment use of an ID to be ethical. These include a justified need for the use of an ID, no threat to clinical development of the ID, adequate scientific evidence to support the treatment, patient’s benefit as the primary goal of the use of an ID, informed decision of a patient, fair access of patients to IDs, independent review, as well as the dissemination of treatment results. Conclusions While this framework is essentially consistent with the legal regulations of expanded access of the USA, the EU, Canada and Australia, it is substantially wider in scope because it addresses some important issues that are not covered by the regulations. Overall, the framework that we developed minimizes the risks and threats, and maximizes potential benefits to each of the four key stakeholders involved in the treatment use of IDs including patients, doctors, drug manufacturers, and society at large.

Background: Importance of awareness of medical ethics and its integration into medical curriculum has been frequently highlighted. Study 1 aimed to assess the knowledge, attitude, and reported practices of medical ethics among clinicians at Patan Academy of Health Sciences, a tertiary care teaching hospital in Nepal. Study 2 was conducted to assess whether there was a difference in knowledge, attitude, and reported practices of medical ethics among doctors who received formal medical ethics education during undergraduate studies and those who did not.Methods: Two cross-sectional surveys using self-administered questionnaires were conducted. Study 1 included 72 participants; interns, medical officers, and consultants working at Patan Academy of Health Sciences. Study 2 was a comparative study conducted among 54 medical officers who had received formal medical ethics education (Group 1) and 60 medical officers who did not (Group 2).Results: Participants who had completed post-graduate education had higher knowledge (p = 0.050), practice (p < 0.001), and overall combined scores (p = 0.011). Participants with ethics education had higher knowledge (p < 0.001), attitude (p = 0.001), practice (p < 0.001), and overall score (p < 0.001). Most participants preferred consulting colleagues if an ethical dilemma arose. Fewer participants had heard of the Declaration of Helsinki. Most participants thought doctors to be most capable of judging what is best for the patient (Study 1: 70.42%, Study 2 Group 1: 42.59%, Group 2: 80%). Case scenarios in which participants demonstrated poor practice were ethical issues concerning truth-telling, end-of-life decisions, treating HIV/AIDS patients, treating a minor, and reporting colleague's errors.Conclusions: This study found that participants who have received medical ethics education have higher knowledge, attitude, and practice scores. The results further justify the need for medical ethics education to be a part of the core medical curriculum. A blame-free environment where seniors can be approached for advice should be created. Research ethics should also be given attention. During medical ethics training, ethical issues where doctors perform poorly should be given more priority and should be discussed in a country-specific context. [ABSTRACT FROM AUTHOR]

Background: Patients with COVID-19 may feel under pressure to participate in research during the pandemic. Safeguards to protect research participants include ethical guidelines [e.g. Declaration of Helsinki and good clinical practice (GCP)], legislation to protect participants' privacy, research ethics committees (RECs) and informed consent. The International Committee of Medical Journal Editors (ICMJE) advises researchers to document compliance with these safeguards. Adherence to publication guidelines has been suboptimal in other specialty fields. The aim of this rapid review was to determine whether COVID-19 human research publications report compliance with these ethical safeguards.Methods: A rapid systematic literature review was conducted in MEDLINE using the search term 'COVID-19'. The search was performed in April 2020 with no start date and repeated to include articles published in November 2020. Filters were 'Full free text available' and 'English Language'. Two reviewers assessed article title, abstracts and full texts. Non-COVID-19 articles and non-clinical studies were excluded. Independent reviewers conducted a second assessment of a random 20% of articles. The outcomes included reporting of compliance with the Declaration of Helsinki and GCP, REC approval, informed consent and participant privacy.Results: The searches yielded 1275 and 1942 articles of which 247 and 717 were deemed eligible, from the April  search and November respectively. The majority of journals had editorial policies which purported to comply with ICMJE ethical standards. Reporting of compliance with ethical guidelines was low across all study types but was higher in the November search for case series and observational studies. Reporting of informed consent for case studies and observational studies was higher in the November search, but similar for case series. Overall, participant confidentiality was maintained but some case studies included a combination of details which would have enabled participant identification. Reporting of REC approval was higher in the November search for observational studies.Conclusions: While the majority of journal's editorial policies purported to support the ethical safeguards, many COVID-19 clinical research publications identified in this rapid review lacked documentation of these important safeguards for research participants. In order to promote public trust, ethical declarations should be included consistently. [ABSTRACT FROM AUTHOR]

Abstract Objective The 2014 update of the Swiss law on research increases patients' protection; it adds specific requirements for emergency situations, implying an active search for patients' wishes regarding research participation; the possibility of consent waivers is not clearly stated. We explored its practical impact in a RCT on critically ill adults. Methods We considered prospectively collected consents of a multicenter trial addressing the impact of continuous EEG on survival. We assessed the proportions of consents obtained strictly according to the law, of specific waivers for this study obtained from the IRB (early death; relatives' unavailability despite repeated attempts), and the yield of retrieving statements on willingness to research participation. We compared the proportion of consent refusals with those of recent trials in similar environments, and estimated the potential impact on study results. Results Of 402 recruited patients, six had double inclusions, one died before intervention, and 27 (6.7%, alive on long‐term) were excluded following consent refusal or withdrawal, leaving 368 analyzable patients. Specific waivers allowed inclusion of 134 (36.4%) patients, while informed consents were obtained for all others. A statement of willingness to research participation was found in only 14.1%. In recent trials, consent refusal oscillated between 0%–23%, according to different waiver policies. Conclusions Consent waivers should be specifically foreseen to prevent losing a potentially relevant proportion of patients reaching endpoints, and ensure results generalizability. The yield of looking for willingness to research participation seems low; this questions its current usefulness and calls for a public awareness campaign.

Objective: The 2014 update of the Swiss law on research increases patients' protection; it adds specific requirements for emergency situations, implying an active search for patients' wishes regarding research participation; the possibility of consent waivers is not clearly stated. We explored its practical impact in a RCT on critically ill adults. Methods: We considered prospectively collected consents of a multicenter trial addressing the impact of continuous EEG on survival. We assessed the proportions of consents obtained strictly according to the law, of specific waivers for this study obtained from the IRB (early death; relatives' unavailability despite repeated attempts), and the yield of retrieving statements on willingness to research participation. We compared the proportion of consent refusals with those of recent trials in similar environments, and estimated the potential impact on study results. Results: Of 402 recruited patients, six had double inclusions, one died before intervention, and 27 (6.7%, alive on long‐term) were excluded following consent refusal or withdrawal, leaving 368 analyzable patients. Specific waivers allowed inclusion of 134 (36.4%) patients, while informed consents were obtained for all others. A statement of willingness to research participation was found in only 14.1%. In recent trials, consent refusal oscillated between 0%–23%, according to different waiver policies. Conclusions: Consent waivers should be specifically foreseen to prevent losing a potentially relevant proportion of patients reaching endpoints, and ensure results generalizability. The yield of looking for willingness to research participation seems low; this questions its current usefulness and calls for a public awareness campaign. [ABSTRACT FROM AUTHOR]

Background: Informed consent (IC) is essential in defending the autonomy of potential participants in clinical research. Despite the advances in research ethics, particularly in IC, the different guidelines and codes have not been fully implemented. Several studies have presented consent deficiencies that have resulted in unethical practices or poor understanding of the IC., Main Body: This article reviews the evolution of IC, from its philosophical origins and initial use in the Ottoman Empire (16th century) to its use in clinical research today. It also presents the vision of the European project i-CONSENT (Grant Agreement number: 741856), whose main purpose is to improve the understanding of ICs in research and identifies the key components of a new paradigm to develop patient-centred ICs., Conclusions: In many cases, the IC has served to protect the investigator or sponsor from complaints. Different ethical guidelines have sought to make the IC a more useful tool, with little success. Today's IC is mainly a bureaucratic and legal process that fails to consider the patient's point of view. In this context, the Guidelines for Tailoring the Informed Consent Process in Clinical Studies provide alternatives to the current IC process, focusing on the patient's opinions and making them part of the process, thereby improving clinical research quality., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Fons-Martinez J et al.)

The World Medical Association's Declaration of Helsinki is in the process of being revised. The following amendments are recommended to be incorporated in pursuit of the common goal of promoting health for all. 1. Data-driven research that facilitates broad informed consent and dynamic consent, assuring participant's rights, and the sharing of individual participant data (IPD) and research results to promote open science and generate social value. 2. Risk minimisation in a placebo-controlled study and post-trial access to the best-proven interventions for all who need them. 3. A future-oriented research framework for co-creation with all the relevant stakeholders., Competing Interests: JS is an owner and executive consultant of PPH plus GmbH & Co. KG. AC is employed by Pfizer Healthcare Ireland. VB is president of IFAPP. SK-F declares that he serves as Associate Editor in Frontiers in Medicine and Frontiers in Pharmacology, and CK serves as a reviewer of Frontiers in Pharmacology. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kurihara, Kerpel-Fronius, Becker, Chan, Nagaty, Naseem, Schenk, Matsuyama and Baroutsou.)

Expansion of data-driven research in the 21st century has posed challenges in the evolution of the international agreed framework of research ethics. The World Medical Association (WMA)’s Declaration of Helsinki (DoH) has provided ethical principles for medical research involving humans since 1964, with the last update in 2013. To complement the DoH, WMA issued the Declaration of Taipei (DoT) in 2016 to provide additional principles for health databases and biobanks. However, the ethical principles for secondary use of data or material obtained in research remain unclear. With such a perspective, the Working Group on Ethics (WGE) of the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine (IFAPP) suggests a closer scientific linkage in the DoH to the DoT focusing specifically on areas that will facilitate data-driven research, and to further strengthen the protection of research participants.

Abstract Background In October 2013, the Declaration of Helsinki was revised a seventh time in its 50 year history. While it is the most widely accepted set of ethical principles for the protection of patients participating in medical research, the Declaration of Helsinki has also been subject of constant controversy. In particular, its paragraph on the use of placebo controls in clinical trials divides the research community into active-control and placebo orthodox proponents, both continuously demanding revisions of the Declaration of Helsinki in favour of their position. The goal of the present project is to compare the mainly theoretical controversy with regulatory implementation. Methods We distributed a questionnaire to national drug regulatory authorities from different countries to collect information on the authorities’ respective approaches to interpretation and implementation of the Declarations’ placebo paragraph in the conduct of medical research. Results Our findings suggest that the majority of drug regulatory authorities have established a practice of a middle ground, allowing placebo controls in some instances. Various interpretations of “serious harm” and “methodological reasons” are proposed as well as safeguards to avoid abuse of the option to use placebo-controls. Conclusion Leaving the placebo paragraph open to various interpretation is a result of the Declaration of Helsinki’s character as a guidance document. With the current version controversy will continue. The Declaration should be continued to be strengthened to enforce the appreciation of conducting medical research with the highest ethical standard.