Institutional ethics review of clinical study agreements

Clinical Study Agreements (CSAs) can have profound effects both on the protection of human subjects and on the independence of investigators to conduct research with scientific integrity. Sponsors, institutions, and even investigators may fail to give adequate attention to these issues in the negotiation of CSAs. Despite the key role of CSAs in structuring ethically important aspects of research, they remain largely unregulated and unreviewed for adherence to ethical norms. Academic institutions routinely enter into research contracts that fail to meet adequate ethical standards. This is a failing that can have serious consequences. Accordingly, it is necessary that some independent body have the authority both to review research contracts for compliance with norms of subject protection and ethical integrity, and to reject studies that fail to meet ethical standards. Such review should take place prior to the start of research, not later. Because of its expertise and authority, the institutional ethics review board (IRB or REB) is the appropriate body to undertake such review. Much recent commentary has focused on contractual restrictions on the investigator's freedom to publish research findings. The Olivieri experience, and that of other investigators, has brought freedom of publication issues into sharp focus. Clinical study agreements also raise a number of other ethical issues relating to human subjects and research integrity, however, including disclosures relating to patient safety, data analysis and reporting, budget, confidentiality, and premature termination of the study. This paper describes the ethical issues at stake in structuring such agreements and suggests ethical standards to guide institutional ethics review.     

Palliative care research: trading ethics for an evidence base

Good medical practice requires evidence of effectiveness to address deficits in care, strive for further improvements, and justly apportion finite resources. Nevertheless, the potential of palliative care is still held back by a paucity of good evidence. These circumstances are largely attributable to perceived ethical challenges that allegedly distinguish dying patients as a special client class. In addition, practical limitations compromise the quality of evidence that can be obtained from empirical research on terminally ill subjects. This critique aims to appraise the need for focused research, in order to develop clinical and policy decisions that will guide health care professionals in their care of dying patients. Weighted against this need are tenets that value the practical and ethical challenges of palliative care research as unique and insurmountable. The review concludes that, provided investigators compassionately apply ethical principles to their work, there is no justification for not endeavouring to improve the quality of palliative care through research.     

Protecting the privacy of family members in survey and pedigree research

The recent controversy at Virginia Commonwealth University involving research ethics raises important and complex issues in survey and pedigree research. The primary questions are whether family members of survey respondents themselves become subjects of the project and if they are subjects whether informed consent must be obtained for investigators to retain private information on these individuals. This article provides an analysis of the ethical issues and regulatory standards involved in this debate for consideration by investigators and institutional review boards. The analysis suggests that strong protections for the rights and welfare of subjects and their family members can be incorporated into survey and pedigree research protocols without hindering projects with extensive consent requirements.     

Balancing the scales of public interest: medical research and privacy

Guidelines for the protection of privacy in the conduct of medical research have been issued by the National Health and Medical Research Council, approved by the Commonwealth Privacy Commissioner, and gazetted on 1 July 1991 (Commonwealth of Australia Gazette No. P19) to remain in force until 30 June 1994. This paper examines the guidelines and seeks to inform researchers, institutional ethics committees and the institutions those committees represent of their content. Responsibilities are placed upon those engaged in the conduct of research and those involved in undertaking ethical review who now have to decide that the public interest in conducting the research substantially outweighs the public interest in privacy. There is also an emphasis on the requirement for surveillance of research projects by institutional ethics committees which has not previously been apparent. Questions are posed to assist in deciding whether a particular research protocol is subject to the guidelines.     

Status of informed consent in the original articles published in a medical journal of Bangladesh

Informed consent and other ethical issues are included in every guideline of research ethics. Taking informed consent from the participants is essential in human health research. The health researchers are not addressing adequately the issues of informed consent and other relevant issues. In many of the published articles in our country, there is no mention of informed consent and other relevant ethical issues. In this study, a 5-years retrospective review was performed on the original articles that described research involving human subjects, and published in the "Journal of Bangladesh College of Physicians and Surgeons" in the period of 1999 to 2003. The objectives of this review were: i) to document whether the author has mentioned about informed consent in the published original article; and ii) to document whether the author has addressed the informed consent procedure in appropriate details. Fifty three original articles were reviewed, only in 7(13.2%) articles the author has mentioned that informed consent was taken from the participants. In 19 (63%) articles, where the subjects were minors or incompetent, there was no mention from whom informed consent was taken. Only in 2(3.7%) articles, the authors have mentioned about the approval of Ethical Review Committee, and in 4(7.5%) articles about the funding agency. Other ethical issues were also ignored. The study documents deficiencies in informed consent and relevant ethical issues in the published articles. This finding demands greater attention to ethical standards on the part of investigators and the editors.     

Rationing, randomizing, and researching in health care provision

In this paper the need for valid evidence of the cost-effectiveness of treatments that have not been properly evaluated, yet are already available, albeit in short supply, are examined. Such treatments cannot be withdrawn, pending proper evaluation, nor can they be made more widely available until they have been shown to be cost-effective. As a solution to this impasse the argument put forward recently by Toroyan et al is discussed. They say that randomised controlled trials of such resources could be done but only if resources are randomly allocated independently of a research context. Relevant outcome data could then be collected for research, given this opportunity. (There are already a few investigators who have turned limited resources, mostly health service provision, to their advantage in this way.) We agree. We disagree with Toroyan et al on a number of points. First, they claim that no ethical issue relating to equipoise arises. We disagree and this disagreement depends on our showing that equipoise should be maintained in a relationship that they do not consider. Secondly, they say that consent to data collection is always needed. Again we disagree. Thirdly, they claim that the previous two issues are the only possible ethical issues that could arise. We argue, instead, that there is a further conflict of interests that has ethical import.     

Ethical dilemmas for general practitioners under the UK new contract.

Possible distributive justice frameworks for providing health care by general practitioners are discussed. The ethical considerations before and after the recent changes to the British National Health Service are contrasted, with particular emphasis on a possible ethical divide that has been produced between fund-holding and non-fund-holding general practitioners. It is argued that general practitioners in non-fund-holding practices can continue as ethical advocates for their patients and distribute health care within an egalitarian framework. However, those in fund-holding practices may now be seen as interest advocates and may have to practise utilitarian distributive justice. Patient groups may be needed to ensure that these general practitioners are seen to act justly in the distribution of the health care resources for which they are now responsible.     

Duty to disclose what? Querying the putative obligation to return research results to participants

Many research ethics guidelines now oblige researchers to offer research participants the results of research in which they participated. This practice is intended to uphold respect for persons and ensure that participants are not treated as mere means to an end. Yet some scholars have begun to question a generalised duty to disclose research results, highlighting the potential harms arising from disclosure and questioning the ethical justification for a duty to disclose, especially with respect to individual results. In support of this view, we argue that current rationales for a duty of disclosure do not form an adequate basis for an ethical imperative. We review policy guidance and scholarly commentary regarding the duty to communicate the results of biomedical, epidemiological and genetic research to research participants and show that there is wide variation in opinion regarding what should be disclosed and under what circumstance. Moreover, we argue that there is fundamental confusion about the notion of "research results," specifically regarding three core concepts: the distinction between aggregate and individual results, amongst different types of research, and across different degrees of result veracity. Even where policy guidance and scholarly commentary have been most forceful in support of an ethical imperative to disclose research results, ambiguity regarding what is to be disclosed confounds ethical action.     

The experiences of ethics committee members: contradictions between individuals and committees

The current system of ethical review for medical research in the United Kingdom is changing from the current system involving large committees of 7-18 members reviewing every individual application to a system involving pre-review by small sub-committees of National Research Ethics Officers (NREAs), who have a remit to approve studies if they believe there are no material ethical issues imposed by the research. The reliability of this new system depends on the reliability of the NREAs and in particular the ability of small groups to effectively identify and appropriately assess the seriousness of all the material ethical issues that may be posed by an application. There is anecdotal evidence to suggest that many individual research ethics committee members have had experience of believing that a study presents no material ethical concerns, then on reaching the committee and discussing the application they realise that the committee feels it does present significant ethical concerns. If this is the case then this casts doubt on the reliability of NREAs or small groups to effectively identify ethically problematic research and appropriately respond to this to protect research participants. In this paper we describe a small questionnaire based piece of research carried out to assess how common this and other relevant experiences are.     

A review of adjuvants for Leishmania vaccine candidates

Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to antigens has led many researchers to re-focus their vaccine development programs. Although several vaccine candidates have been tested against leishmaniasis, there is yet no effective vaccine against this parasitic disease. Recent research has documented that efforts to develop effective Leishmania vaccine have been limited due to lack of an appropriate adjuvant. In view of this, this review paper outlines some of the adjuvants that have been used in Leishmania vaccine candidates and cites a few of the responses obtained from these studies. The aim of the present review is to consolidate these findings to facilitate the application of these adjuvants in general and experimental vaccinology.     

Ethical dilemmas in malaria vector research in Africa: Making the difficult choice between mosquito,science and humans

Malaria vector studies are a very important aspect of malaria research as they assist researchers to learn more about the malaria vector. Research programmes in various African countries include studies that assess various methods of preventing malaria transmission including controlling the malaria vector. Various institutions have also established mosquito colonies that are maintained by staff from the institutions. Malaria vector research presents several dilemmas relating to the various ways in which humans are used in the malaria vector research enterprise. A review of the past and present practices reveals much about the prevailing attitudes and assumptions with regard to the ethical conduct of research involving humans. The focus on the science of malaria vector research has led some researchers in African institutions to engage in questionable practices which reveal the ethical tensions inherent in the choice between science and the principles of justice, nonmaleficence and respect for individuals. The analysis of past and present choices in malaria vector research has relevance to broader questions of human dignity and are in line with the current emphasis on ethical research worldwide.     

Informed consent for research: international perspectives

Problems in obtaining and documenting informed consent are especially difficult to resolve in countries whose cultures differ considerably from those of most Western nations. Confusion between the research and therapeutic contexts are widespread. Two departures from widely accepted ethical standards are discussed: withholding information about the research and requiring a husband's permission for his wife to participate. Supporters of such departures claim that they are justified by the cultural context of the country in which the research is carried out. One program at the World Health Organization has developed guidelines stating that requiring partner agreement or authorization for an individual to participate in research violates the autonomy of research subjects and their right to confidentiality. A study carried out at one reproductive health clinic in Chile describes a process of obtaining informed consent to research that could serve as a model for US investigators interested in making informed consent a meaningful and ethically respectable aspect of their research activities. Research involving human subjects should adhere to a single, universally applicable standard of informed decision making by participants.     

Medical records: practicalities and principles of patient possession.

This review of issues and research is in two parts: 1) practical problems surrounding patient-held records and 2) ethical arguments for and against patient-held records. We argue that research on patient-held records indicates that there are no substantial practical drawbacks and considerable ethical benefits to be derived from giving patients custody of their medical records.     

Professional Integrity in Clinical Research

In response to public concern over abuses in human medical experimentation, the dominant approach to the ethics of clinical research during the past 30 years has been regulation, particularly via institutional review board review and approval of scientific protocols and written consent forms. However, the effectiveness of regulatory mechanisms in ensuring the ethical conduct of clinical research is limited. Little attention has been devoted to the nature and role of professional integrity of physician investigators, a conscientious framework for guiding investigators in the socially important but morally complex activity of clinical research. Professional integrity is vital in forging an ethically sound relationship between investigators and patient volunteers, a relationship that differs in important ways from the patient-physician relationship in standard clinical practice. We examine critically 2 models of the moral identity of physician investigators, the investigator as clinician and the investigator as scientist; in neither of these 2 models can the physician investigator eliminate completely the moral conflicts posed by clinical research. The professional integrity of physician investigators depends on a coherent moral identity that is proper to the enterprise of clinical research. The roles of clinician and scientist must be integrated to manage conscientiously the ethical complexity, ambiguity, and tensions between the potentially competing loyalties of science and care of volunteer patients.      

Ethics review of research: in pursuit of proportionality

The ethics review system of research is now well-established, at least in the developed world, although there are many differences in how countries view it and go about managing it. The UK specifically is now seeking to revise its system by speeding up the process of ethics approval but only for some studies. It is proposed that only those studies which pose "no material ethical issues" should be "fast-tracked". However, it is unclear what this means, who should decide and what should be included in this category. In this paper, we go some way towards answering these questions. While we are certain that the debate is only just beginning, we are equally certain that it will continue to run long after the system has been reformed. To stimulate this conversation and to inform a pilot project of the new system directly, we review two candidates to help give some substance to the notion of "material" ethical issues. Firstly, material could mean a certain type or degree of risk. Second, material could mean how physically invasive the research is. We conclude that there is still much work to be done on making the system of governing health and social care consistent and practicable.     

“Because you're worth it?” The taking and selling of transplantable organs

In the UK, the legal processes underpinning the procurement system for cadaveric organs for transplantation and research after death are under review. The review originated after media reports of hospitals, such as Alder Hey and Bristol, retaining organs after death without the full, informed consent of relatives. The organ procurement systems for research and transplantation are separate and distinct, but given that legal change will be applicable to both, some have argued now is the time to introduce alternative organ transplant procurement systems such as presumed consent or incentive based schemes (despite inconclusive British and American research on the status of public attitudes). Findings are reported in this paper from qualitative and quantitative research undertaken in Scotland in order to ascertain the public acceptability of different procurement systems. Nineteen in depth interviews carried out with donor families about their experiences of donating the organs of the deceased covered their views of organ retention, presumed consent, and financial incentives. This led onto a representative interview survey of 1009 members of the Scottish public. The originality of the triangulated qualitative and quantitative study offers exploration of alternative organ procurement systems from different "sides of the fence". The findings suggest that the legal changes taking place are appropriate in clarifying the role of the family but can go further in strengthening the choice of the individual to donate.     

Research, ethics and conflicts of interest.

In this paper, I have tried to develop a critique of committee procedures and conflict of interest within research advisory committees and ethical review committees (ERCs). There are specific features of conflict of interest in medical research. Scientists, communities and the subjects of research all have legitimate stakeholdings. The interests of medical scientists are particularly complex, since they are justified by the moral and physical welfare of their research subjects, while the reputations and incomes of scientists depend on the success of their science. Tensions of this kind must at times produce conflict of interest. It is important to recognise that conflicts of interest may unwittingly lead to manipulation of research subjects and their lay representatives on research committees. It is equally important to recognise distinctions between the legal and moral aspects of conflict of interest. Some practical suggestions are made which may go some way towards resolving these difficulties. They indicate what might be needed to ensure the validity of ethical discourse, and to reduce the risks associated with conflict of interest.     

In the lion's den? Experiences of interaction with research ethics committees

Research ethics review is an important process, designed to protect participants in medical research. However, it is increasingly criticised for failing to meet its aims. Here, two researchers reflect on their experiences of applying for ethical approval of observational research in clinical settings. They highlight some problems faced by reviewers and researchers and propose a two-stage ethical review process that would alert researchers to the committee's concerns and allow them to give a more considered response.     

Ethics in systematic reviews

Since its introduction by the Nuremberg Code and the Declaration of Helsinki, the place held by ethics in biomedical research has been continuously increasing in importance. The past 30 years have also seen exponential growth in the number of biomedical articles published. A systematic review of the literature is the scientific way of synthesising a plethora of information, by exhaustively searching out and objectively analysing the studies dealing with a given issue. However, the question of ethics in systematic reviews is rarely touched upon. This could lead to some drawbacks, as systematic reviews may contain studies with ethical insufficiencies, may be a possible way to publish unethical research and may also be prone to conflict of interest. Finally, informed consent given for an original study is not necessarily still valid at the systematic review level. There is no doubt that routine ethical assessment in systematic reviews would help to improve the ethical and methodological quality of studies in general. However, ethical issues change so much with time and location, and are so broad in scope and in context that it appears illusory to search for a universal, internationally accepted standard for ethical assessment in systematic reviews. Some simple suggestions could nevertheless be drawn from the present reflection and are discussed in the paper.     

医疗技术专门伦理委员会的建立与必要性

从医院工作实际分析,科学研究与新医疗技术引进存在差异,引进是重点。引进的新医疗技术属于临床医疗服务项目,故设立医疗技术伦理委员会可使该范围内伦理审查更具操作性,避免将成熟技术引进人为改变为研究。但伦理审查不可或缺,以保障医疗质量安全、提高医疗服务能力。审查重点是限制类医疗技术,不接受禁止类医疗项目;审查内容包括资质、设备条件及安全保障措施等;审查仍需遵循伦理学原则。