Ethical regulation of biomedical research in Hungary

Hungary joined the Ovideo Treaty (a bioethical health agreement signed by EU countries in 1997), as declared by Law Nr. VI in 2002. In July 1 2002 two departmental orders were enacted: departmental order Nr. [23/2002 (V. 9.)] about the biomedical research in humans and departmental order Nr. [24/2002 (V. 9.)] about the human use and clinical trials of investigational products and the adaptation of Good Clinical Practice (GCP). Both were based on the Health Law. The departmental order on the Medical Research Council [(16/2001 (IV. 28.)] together with these two orders contains the national rules of biomedical research performed in Hungary and also the Hungarian adaptation of various, bioethical principles and directives published by EU or other internationally accepted organisations. According to these regulations from 2002 biomedical research in Hungary could be in agreement with the Oviedo Treaty. Ethical approval and supervision can be obtained from research ethical committees of three types: central, regional and local superimposed upon one another. There are three, central, ethical committees within the frames of the Medical Research Council with national responsibility: Scientific and Research Ethical Committee, Clinical Pharmacological Ethical Committee, Human Reproduction Committee. In some cases regional research ethical committees are entitled to hand out ethical approval and ethical supervision. In those research sites, where the regional research ethical committee is not existent a local committee should be organized for the local ethical control of the research investigations and experiments. This way the ethical requirements and clinical practice by the GCP can be performed in clinical research in Hungary with a special respect to the vulnerable persons possibly involved. The paper gives an overview on recent developments and major ethical principles of the Hungarian biomedical research.     

Ethics are local: engaging cross-cultural variation in the ethics for clinical research.

Relatively little consideration has heretofore been given to the interaction between Western clinical research ethics and non-Western ethical expectations. How should any conflict that might arise when a biomedical investigator and a research subject come from different cultural settings and have different ethical expectations be addressed? Which ethics should govern such trans-cultural clinical research? The answers to these questions are of increasing importance because many countries of the developing world are presently sites of field testing of biomedical agents sponsored and administered by countries of the developed world, especially in the context of the AIDS pandemic. Drawing mainly on examples from Asian medical systems and settings, I elucidate four possible ethical models to guide the conduct of transcultural biomedical research. Two assume that research ethics are culturally relative and two assume that a unified, universalistic conceptualization of research ethics is possible. All four, however, are problematic and are to a large extent deficient. The cause of the deficiencies of these models lies, I argue, in the way that ethics are ordinarily conceived. The proper approach to ethical conflict recognizes that culture shapes (1) the content of ethical precepts, (2) the form of ethical precepts, and (3) the way ethical conflict is handled. Medical ethics may be viewed in cross-cultural perspective as a form of 'local knowledge', and any differences in such knowledge between cultures--since such differences will not conveniently disappear--must be engaged and negotiated.     

An exploration of ethical issues in research in children's health and the environment

The consideration of ethical issues relating to pediatric environmental health is a recent phenomenon. Discussions of biomedical ethics, research on children, and environmental health research have a longer history. In the late 1990s, researchers at the Kennedy Krieger Institute in Baltimore, Maryland, undertook a study to compare the effectiveness of several methods of reducing lead risk in housing. In a preliminary finding in the case of Grimes v. Kennedy Krieger Institute, Inc., a Maryland court questioned the ethics of performing research on children when there is no prospect of direct benefit to those children and whether parents can consent to such research. This case dramatically raised the profile of ethical issues among the pediatric environmental health research community. To broaden the discussion of these issues and in response to the Kennedy-Krieger case, the Children's Environmental Health Network held a working meeting on 5 and 6 March 2004 to explore this topic. The articles in this mini-monograph were prepared by the authors as a result of the workshop and represent their opinions. This article is an introduction to the workshop and a summary of the articles to follow.     

Ethics guidelines for the creation and use of registries for biomedical research purposes

The clinical information stored in registries and records of different types is a fundamental tool for biomedical research. Up until just a few years ago, hardly any limitations existed on the creation and use of epidemiological registries or the use of information from pre-existing records for research purposes. This situation has changed substantially due mainly to the growing importance current laws place upon the safeguarding of the privacy and confidentiality of personal data. Although the legal framework is already quite explicit, a certain degree of leeway exists for ethical debate and prudence advice for the purpose of conducting valid, useful research with this information which will also respect the rights of the subjects and the laws in force. These guidelines deal with those aspects which have been considered relevant from an ethical standpoint in the handling of records and registries for research-related purposes, including not only the use but also the creation proper of the registries. A total of twenty-four recommendations are provided, grouped into ten sections: warranting of the creation of registry, organization and definition of responsibilities, scientific validity of the research project, ethical requirements of the collections of anonymous and anonymized data, ethical requirements of the registries including personal data, uses of medical records for research purposes, use of historical records of deceased individuals, contact with the research subjects, notification of results and review by a Research Ethics Committee.     

The Institute of Medicine, National Academy of Sciences: formulating AIDS policy

In 1985 the Institute of Medicine, National Academy of Sciences devoted its annual meeting to an exploration of acquired immunodeficiency syndrome (AIDS). The questions raised at the meeting propelled the IOM/NAS to initiate an assessment of the dimensions of the AIDS epidemic and to propose an appropriate national response. The Committee on a National Strategy for AIDS issued its report, "Confronting AIDS: Directions for Public Health, Health Care, and Research," in October 1986. The report detailed strategies for curbing the spread of infection, and for accelerating biomedical and social science research into the causes and possible cures for AIDS. In March 1987, the IOM/NAS established the AIDS Activities Oversight Committee to monitor and assess the nation's progress against AIDS and to coordinate the Academy's growing program of AIDS-related activities. Studies, conferences, and workshops are planned in the areas of drug and vaccine development, modeling the course of the epidemic, research in the behavioral and social sciences, equitable financing of care, pediatric AIDS, early cognitive impairment in HIV infection, IV drug abuse, and other topics.     

医学论文写作时应注意的伦理道德问题

随着人类文明不断进步,社会和谐发展逐渐受到研究者的重视,医学作为直接面对人的科学比其他学科更强调人文主义.医学科研人员在进行科学研究时,所研究的项目不仅要具有科学性和创新性,而且更要注重伦理道德问题.国内外越来越多的生物医学期刊开始注重医学论文的伦理道德问题.本文结合国际期刊编辑委员会2010年发表的《向生物医学期刊投稿的统一要求》及出版物伦理委员会所关心的问题,结合医学论文写作中需要注意的伦理道德问题作一综述.     

Establishing a national biobank. Biobanking infrastructure initiative in Slovakia - Public policy,legal and ethical issues

Resulting from a multi-stakeholder initiative in 2017, a rapid process is underway in Slovakia with the aim of establishing a national system of biobanks by 2020. A combined top-down and bottom-up approach is being followed under the leadership of the Ministry of Health Institute for Research and Development. Relevant national stakeholders, with international expert partner institutions providing additional know how and networking, have been successfully involved since the very beginning of this initiative. State-of-the-art biobanking facilities are to be built in order to accommodate the Slovak National Biobank in the city of Martin (Central Slovakia) and the other major biobank in the city of Košice (Eastern Slovakia), while existing structures – future local biobanks – will be upgraded to achieve complete technical and logistical compatibility. This should enable full compliance of the Slovakia's biobanking system with the appropriate international ethical, legal and professional standards. A related legislative activity has been started, aimed at a comprehensive updating of the existing Slovak biomedical research and health care legislation, to provide for the necessary legal certainty. After successful completion of the Initiative, the Slovakia's biomedical research infrastructure is to be better set for supporting excellent domestic research and development efforts, as well as for its involvement in high-quality international research collaborations and partnerships.     

How should cost-effectiveness analysis be used in health technology coverage decisions? Evidence from the National Institute for Health and Clinical Excellence approach

BACKGROUND: In the National Health Service in England and Wales, technology coverage decisions are taken by the National Institute for Health and Clinical Excellence (NICE). The intention formally to apply cost-effectiveness analysis to the decision-making process distinguishes NICE from most other bodies making similar policy recommendations. We carried out a case study of the NICE Appraisals Committee to explore the influence and use of economic evaluation in the decision-making process. METHODS: Qualitative case study methodology. This involved analysis of all relevant secondary sources, observations of Appraisals Committee deliberations and interviews with a cross-section of Committee members. FINDINGS: Economic evaluation is integrated into the Committee's work. There are two main ways in which the use of economic analysis is understood by Committee members: an ordinal approach, whereby cost-effectiveness is only considered if the technology has passed a clinical effectiveness hurdle; and a framework approach, whereby the economic evaluation and model provide a structure for considering the decision problem and the evidence. These two approaches appear to operate simultaneously but are, in essence, inconsistent. CONCLUSIONS: The NICE 'experiment' has seen cost-effectiveness analysis move to the centre-ground of UK national policy deliberations regarding technology coverage. However, our case study implies that there may be room for further refinement of the appraisal process in order to resolve the observed tension between two different ways of incorporating cost-effectiveness analysis in NICE's decision-making.     

Health research ethics review and needs of institutional ethics committees in Tanzania

This study was undertaken to describe the performance of health research ethics review procedures of six research centres in Tanzania. Data collection was done through a self-administered questionnaire and personal interviews. The results showed that there were on average 11 members (range = 8-14) in each Research Ethic Committee. However, female representation in the committees was low (15.2%). The largest proportion of the committee members was biomedical scientists (51.5%). Others included medical doctors (19.7%), social scientists (7.6%), laboratory technologists (10.6%), religious leaders (4.5%), statisticians (3.0%), teachers (1.5%) and lawyers (1.5). Committee members had different capacities to carry out review of research proposals (no capacity = 2%; limited capacity = 15%; moderate capacity = 20%; good capacity = 48%, excellent capacity = 13%). Only half of the respondents had prior ethics review training. Although the majority deemed that ethical guidelines were very important (66%), there were challenges in the use of ethical guidelines which included lack of awareness on the national accreditation mechanisms for ethics committee (59%). Adherence to ethical principles and regulations was influenced by being a scientist (OR = 42.47), being an employee of a professional organization (OR = 15.25), and having an interests in the use of ethical guidelines (OR = 10.85) These findings indicate the need for capacity strengthening (through training and resource support), inclusion of more female representation and other mandatory professions to the research ethics committees.     

Public Advocacy and Allocation of Federal Funds for Biomedical Research

Members of Congress and officials of the National Institutes of Health face heightened pressure from public advocacy groups seeking more funding for research on specific health conditions. In response, Congress and the Institute of Medicine have urged the NIH to create more opportunities for the public to participate in decision making on allocation of biomedical research resources. The ethical and policy implications of including advocates in the deliberations are explored, leading to the conclusion that public participation could contribute to more defensible decisions under three conditions: public participants are fairly selected and meaningful opinions are solicited; public participants look beyond their narrow constituencies to consider the health needs of the broader public; and NIH officials develop materials to assist participants with their deliberations.     

Strengthening biostatistics resources in sub-Saharan Africa: research collaborations through U.S. partnerships

On September 30, 2009, the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) conducted a workshop on strengthening biostatistics resources in sub-Saharan Africa (SSA). An increase in global spending on health research over the last decade has boosted funds available to conduct biomedical research in low- to mid-income countries. The HIV/AIDS pandemic, the re-emergence of malaria and tuberculosis, and other emerging infectious agents are major driving forces behind the increase in biomedical research and clinical care programs (clinical trials, observational studies and, other public health programs) in SSA (Exp. Biol. Med. 2008; 233:277-285). In addition, the increased engagement of the United States (U.S.) government through the Global Health Initiative, which expands the traditional focus beyond infectious diseases to other causes of poor health and to the recognition of need the to strengthen health systems for a sustainable response, only increases the need for in-depth in-country expertise in all aspects of biomedical research (White House Press Release, 2009). In this workshop, researchers both from the U.S. and SSA were invited to discuss their collaborative work, to discuss ways in which biostatistical activities are carried out within their research projects, and to identify both general and specific needs for capacity building in biostatistics. Capacity building discussions highlighted the critical need to increase the number of well-trained in-country biostatisticians, both to participate in ongoing studies and to contribute to an infrastructure that can produce the next generation of biostatistical researchers.     

HoMER - an opportunity or threat to general practice research?

The National Health and Medical Research Council (NHMRC) Harmonisation of Multicentre Ethical Review (HoMER) project aims to implement a 'single ethical review', where the outcome of an ethical and scientific review by a single recognised Human Research Ethics Committee (HREC) will enable multiple institutions to decide whether or not to participate in a given study. The desired process will include agreement on time frames, authority of the reviewing HREC, respect among the jurisdictions, verification by independent organisations, and compliance with the national statement and relevant statutory and administrative frameworks. However, there appears to be little discourse on the implications for general practice research in the research community.     

Unnecessary delays in ethical approval of multicentre clinical trials

Medical ethical committees and institutional review boards serve to protect patients and healthy volunteers participating in research projects. Among clinical researchers there exists a general feeling that, although the importance of protecting research subjects is acknowledged, obtaining approval for a research protocol takes too much time, especially in the case ofmulticentre clinical trials. The Dutch Ministry of Health, Welfare and Sport and the Central Committee on Research involving Human Subjects (CCMO) have tried to streamline and shorten the approval process, but so far these efforts have failed. The failure can be attributed not only to the ethical committees but also to the investigators and hospital management. It is argued that lack of knowledge of the application rules and failure by all parties to observe the appropriate procedures are the major causes of delay. If all involved would adhere strictly to the rules and regulations that are already in place, unnecessary delays would be avoided and research applications would obtain approval within 60 days of submission, even in the case ofmulticentre trials.     

Ethical Dilemmas in Community-Based Participatory Research: Recommendations for Institutional Review Boards

National and international codes of research conduct have been established in most industrialized nations to ensure greater adherence to ethical research practices. Despite these safeguards, however, traditional research approaches often continue to stigmatize marginalized and vulnerable communities. Community-based participatory research (CBPR) has evolved as an effective new research paradigm that attempts to make research a more inclusive and democratic process by fostering the development of partnerships between communities and academics to address community-relevant research priorities. As such, it attempts to redress ethical concerns that have emerged out of more traditional paradigms. Nevertheless, new and emerging ethical dilemmas are commonly associated with CBPR and are rarely addressed in traditional ethical reviews. We conducted a content analysis of forms and guidelines commonly used by institutional review boards (IRBs) in the USA and research ethics boards (REBs) in Canada. Our intent was to see if the forms used by boards reflected common CBPR experience. We drew our sample from affiliated members of the US-based Association of Schools of Public Health and from Canadian universities that offered graduate public health training. This convenience sample (n = 30) was garnered from programs where application forms were available online for download between July and August, 2004. Results show that ethical review forms and guidelines overwhelmingly operate within a biomedical framework that rarely takes into account common CBPR experience. They are primarily focused on the principle of assessing risk to individuals and not to communities and continue to perpetuate the notion that the domain of “knowledge production” is the sole right of academic researchers. Consequently, IRBs and REBs may be unintentionally placing communities at risk by continuing to use procedures inappropriate or unsuitable for CBPR. IRB/REB procedures require a new framework more suitable for CBPR, and we propose alternative questions and procedures that may be utilized when assessing the ethical appropriateness of CBPR. Flicker is with the Faculty of Environmental Studies, York University, Toronto, Canada; Travers is with the Ontario HIV Treatment Network, Toronto, Canada; Guta is with the University of Toronto, Toronto, Canada; McDonald is with the Community Based Research Resource Centre, Wellesley Institute, Toronto, Canada; Meagher is with the Mental Health Community Advisory Panel, St. Michael’s Hospital. Toronto, Canada.     

医学期刊编辑对生物医学研究伦理问题的处理方式调研及建议

【目的】 探讨医学期刊编辑处理生物医学研究伦理问题的方式,为推动确立医学期刊伦理审查规范提供参考。【方法】 通过问卷星向国内医学期刊编辑发放调查问卷,对审稿时和论文出版后处理医学伦理相关问题的方式展开调研。【结果】 共回收问卷230份。调查显示:在审稿阶段,在保护患者隐私方面,英文期刊、中英双语期刊的编辑更注重要求作者提供授权同意相关证明材料;中、英文期刊以及中英双语期刊的编辑对涉及人体试验伦理问题的处理方式都比较规范。但是,对于研究是否获得患者知情同意、动物实验研究是否经过伦理委员会审查、回顾性研究是否需要伦理审查、涉及人的研究是否在临床试验注册中心注册等问题,编辑还需要进一步重视。在论文出版后,编辑发现的医学伦理问题主要是“涉及人的研究未说明是否经过伦理委员会审查”。对论文出版后发现的没有保护患者隐私和没有在临床试验注册中心注册的问题,大部分期刊缺乏相关处理方案。【结论】 编辑应加强对论文知情同意、动物实验伦理、回顾性研究伦理的审查,并审查涉及人的研究是否在临床试验注册中心注册,以推动我国医学期刊的高质量发展。     

What deserves our respect? Reexamination of respect for autonomy in the context of the management of chronic conditions

Medicine, Health Care and Philosophy - The global increase in patients with chronic conditions has led to increased interest in ethical issues regarding such conditions. A basic biomedical...     

Clinical evaluation strategies for a live attenuated tetravalent dengue vaccine

Butantan Institute is a public Brazilian biomedical research-manufacturer center affiliated to the São Paulo State Secretary of Health. Currently, Butantan is one of the main public producers of vaccines, antivenoms, and antitoxins in Latin America. The partnership between Butantan and the National Institutes of Health (NIH) of the United Sates has been one of the longest and most successful partnerships in the development and manufacturing of new vaccines. Recently, Butantan Institute has developed and manufactured a lyophilized tetravalent live attenuated dengue vaccine with the four dengue viruses attenuated and licensed from the Laboratory of Infectious Diseases at The National Institutes of Allergy and Infectious Diseases (LID/NIAID/NIH). The objective of this paper is to describe the clinical evaluation strategies of a live attenuated tetravalent dengue vaccine (Butantan-DV) developed and manufactured by Butantan Institute. These clinical strategies will be used to evaluate the Butantan-DV Phase III trial to support the Butantan-DV licensure for protection against any symptomatic dengue caused by any serotype in people aged 2 to 59 years.     

Ethics, politics, and human embryo stem cell research.

Three reports on ethical aspects of research involving human embryonic stem cells were issued in the final months of 1999. Two were from governmental agencies or commissions: the National Institutes of Health and the National Bioethics Advisory Commission. The third report was issued by the American Association for the Advancement of Science and the Institute for Civil Society. All three reports endorse the use of federal funds for embryonic stem cell research, but other differences distinguish these reports. This article describes the differences and provides an ethical analysis of the main arguments.     

Is IQWiG's 15% Threshold Universally Applicable in Assessing the Clinical Relevance of Patient-Reported Outcomes Changes? An ISPOR Special Interest Group Report

This article discusses a recent methodological change to assess the additional benefit of drug intervention by the German Federal Joint Committee (Gemeinsamer Bundesausschuss), a key stakeholder in EUnetHTA21 (European Network for Health Technology Assessment joint consortium for future EU HTA regulation), methodological workstream. The German Federal Joint Committee (Gemeinsamer Bundesausschuss) set a universal individual response threshold at ≥ 15% of the scale range of the measurement instrument, for all patient-reported outcomes, to achieve an additional benefit rating for a given pharmaceutical intervention. This approach is originally based on a corresponding recommendation from the Institute for Quality and Efficiency in Health Care.The merits of this approach are reviewed from various perspectives, including the evidence basis, statistical and psychometric considerations, and regulatory perspectives by the ISPOR Clinical Outcomes Assessment Special Interest Group’s multistakeholder group of authors (academia, contract research organizations, and industry). Particular focus is placed on the patient perspective within the Institute for Quality and Efficiency in Health Care approach.The article development incorporated feedback from ISPOR members during well-attended ISPOR US and European conference presentations and 2 formal rounds of written review. The authors concluded that the ≥ 15% response threshold is incongruent with previously defined and scientifically established thresholds and is not well-suited for universal implementation. Further scientific evidence and discussion among all stakeholders are needed, especially should this universal rule be considered in the context of future joint clinical assessments of health technologies in the European Union scheduled from 2025 onward.     

Community-based participatory research as a tool to advance environmental health sciences

The past two decades have witnessed a rapid proliferation of community-based participatory research (CBPR) projects. CBPR methodology presents an alternative to traditional population-based biomedical research practices by encouraging active and equal partnerships between community members and academic investigators. The National Institute of Environmental Health Sciences (NIEHS), the premier biomedical research facility for environmental health, is a leader in promoting the use of CBPR in instances where community-university partnerships serve to advance our understanding of environmentally related disease. In this article, the authors highlight six key principles of CBPR and describe how these principles are met within specific NIEHS-supported research investigations. These projects demonstrate that community-based participatory research can be an effective tool to enhance our knowledge of the causes and mechanisms of disorders having an environmental etiology, reduce adverse health outcomes through innovative intervention strategies and policy change, and address the environmental health concerns of community residents.