Declaration of Helsinki: ethical norm in pursuit of common global goals.

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.

The Declaration of Helsinki in bioethics literature since the last revision in 2013.

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.

The Sun Also Rises: Tracing the evolution of humanistic values in anatomy pedagogy and research, including cadaveric acquisition practices.

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.

50 years of the first ethics commission in Germany: the Ulm Ethics Commission in an international perspective.

Background: The 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 methods: We 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. Results: The 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. Conclusion: The 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.

Gaps in the evidence underpinning high-risk medical devices in Europe at market entry, and potential solutions.

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.

Ethical analysis of cadaver supply and usage processes for research within the scope of the Helsinki Declaration.

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.

Streamlining clinical research: an ESMO awareness call to improve sponsoring and monitoring of clinical trials.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A Critical Assessment of the Quality of Reporting of Ethical Protections in Medical Papers Published in Turkey.

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.

Does teaching medical ethics ensure good knowledge, attitude, and reported practice? An ethical vignette-based cross-sectional survey among doctors in a tertiary teaching hospital in Nepal.

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.

Taking the principle of the primacy of the human being seriously.

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.

Adherence with reporting of ethical standards in COVID-19 human studies: a rapid review.

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.

Informed consent in critically ill adults participating to a randomized trial.

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.

Linking the Declarations of Helsinki and of Taipei: Critical Challenges of Future-Oriented Research Ethics.

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 (Declaration of Taipei) DoT focusing specifically on areas that will facilitate data-driven research, and to further strengthen the protection of research participants.

Ethics framework for treatment use of investigational drugs.

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.

Corrigendum: Linking the Declarations of Helsinki and of Taipei: Critical Challenges of Future-Oriented Research Ethics.

[This corrects the article DOI: 10.3389/fphar.2020.579714.].

Academic Exchange at WFAS Turkey 2019 and Review of RCTs Conducted in China / 全日本鍼灸学会雑誌

The WFAS Annual Conference 2019 was held between November 14th and 17th at Kaya Palazzo Hotel, Antalya, Turkey. The WFAS executive committee was convened on the 14th. In the EC (Executive Committee) meeting, the JSAM proposed inclusion of the Declaration of Helsinki (DoH) in the WFAS Code of Ethics. Other issues discussed in the EC meeting included approval of the special consultative status by the the United Nations ECOSOC (Economic and Social Council) and preparation of the next WFAS symposium in the Netherlands in 2020. Individual presentations and other exhibitions in the symposium are also introduced in the present report. In addition, recent large-scale RCTs of acupuncture conducted in China were reviewed.

[Ethics review in psychological research]. / Ethikvoten in der psychologischen Forschung.

Psychology, as a fundamental and applied science, studies the behavior of humans with empirical and experimental methods. To this end, volunteers are recruited who reveal information about themselves in either natural or experimental settings. Like medical research, psychological research must obey strict ethical principles (according to the Declaration of Helsinki), because it concerns the self-determination, mental, and physical integrity and privacy of the participants.An assessment of psychological research projects according to ethical criteria is therefore mandatory. Research projects must (i) respect the autonomy and dignity of a person, (ii) promise a substantial gain in knowledge, and (iii) maximize the benefits of the research by minimizing possible disadvantages for the participants; (iv) researchers - committed to their social responsibility - must anticipate the social implications of research findings (possibilities of "dual use").Local ethics committees (LECs) for research projects in psychology work on behalf of a university or faculty. They are to be set up as an independent body. The assessment of ethical safety requires the scientific quality of a research project, but must take into account additional considerations. In this respect, it seems sensible that projects that are to be funded by a third-party funder first establish the scientific eligibility and only then the ethical safety by a LEC.