Using empirical data to inform the ethical evaluation of placebo controlled trials

There has been considerable debate about the ethical acceptability of using placebo-controls in clinical research. Although this debate has been rich in rhetoric, considering that much of this research is predicated upon the assumption that data from this research is vital to clinical decision-making, it is ironic that researchers have introduced little data into these discussions. Using some published research concerning the use of placebo-controls in clinical research in hypertension and psychiatric drug trials, I suggest some ways that such data might be incorporated into the ethical analysis concerning placebo use in clinical trials. This approach promises to be important for enhancing conceptual and scientific understanding as well as public policy decision-making. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

Describing our “humanness”: Can genetic science alter what it means to be “human”?

Over the past several decades, geneticists have succeeded in identifying the genetic mutations associated with disease. New strategies for treatment, including gene transfer and gene therapy, are under development. Although genetic science has been welcomed for its potential to predict and treat disease, interventions may become ethically objectionable if they threaten to alter characteristics that are distinctively human. Before we can determine whether or not a genetic technique carries this risk, we must clarify what it means to be “human”. This paper inquires how “humanness” has been defined within various academic fields. The views of several legal theoreists, scientists, bioethicists, psychologists, philosophers and anthropologists whose works seem to best reflect how “humanness” is understood in their respective fields of study are considered. Our survey attempts to chart a path for a more detailed study on the meaning of “humanness” in the future. We assess four traits commonly identified in the literature as defining what it means to be human: cognition, biological or physiological composition, social interaction with other “human” beings, and spirituality. The nature of the relationship between these characteristics, in our view, is symbiotic: genetic intervention which alters one of them could have repercussions on one or more of the others. In conclusion, we offer guidance to those participating in genetic research and treatment regarding the parameters within which they may proceed without threatening the preservation of what is distinctively human.     

Ethical issues in biomedical research: Perceptions and practices of postdoctoral research fellows responding to a survey

We surveyed 1005 postdoctoral fellows by questionnaire about ethical matters related to biomedical research and publishing; 33% responded. About 18% of respondents said they had taken a course in research ethics, and about 31% said they had had a course that devoted some time to research ethics. A substantial majority stated willingness to grant other investigators, except competitors, access to their data before publication and to share research materials. Respondents’ opinions about contributions justifying authorship of research papers were mainly consistent but at variance with those of many biomedical journal editors. More than half said they had observed what they considered unethical research practices. To increase the chances of getting a grant funded, 27% said they were willing to select or omit data to improve their results; to make publication of their work more likely or to benefit their career, 15% would select or omit data and 32% would list an undeserving author. Of respondents who thought they had been unfairly denied authorship on a paper, or been listed with or asked to list an undeserving author, 75% said they would be willing to list an undeserving author (P<0.001). Having taken a course dealing with research ethics had no effect on stated willingness to select or omit data or to fabricate data in the future, but was positively associated with willingness to grant undeserved authorship (P<0.04). Although these results do not controvert research demonstrating the effectiveness of ethics courses during professional education, they indicate that the research environment is a powerful component of a trainee’s experience and ethical development. Preliminary results of this work were presented in part as a poster at the forumEthics, Values, and the Promise of Science, presented by Sigma Xi, The Scientific Research Society, 25–26 February 1993 in San Francisco, California, USA.     

A Troubled Dance: Doing the Work of Research Ethics Review

The fast growing interest in the work of university ethics review boards is evident in the proliferation of research and literature in the area. This article focuses on a Research Ethics Board (REB) in the Canadian context. In-depth, open-ended interviews with REB members and findings from a qualitative study designed to examine the ethics review of school-based research are used to illustrate points raised in the paper. The author’s experiences as academic researcher, advisor to student researchers and a 3-year term as an REB member inform the discussion. Macro issues related to the general workings of the board (e.g., maintaining appropriate membership) and micro issues connected to individual REB members’ experiences of reviewing research applications are examined. The author’s goal is to contribute to a fastgrowing conversation related to the issues that influence university ethics review while drawing attention to the contribution that faculty members’ understandings of their work as REB members can make to that conversation.     

Scientific societies and research integrity: What are they doing and how well are they doing it?

Scientific societies can play an important role in promoting ethical research practices among their members, and over the past two decades several studies have addressed how societies perform this role. This survey continues this research by examining current efforts by scientific societies to promote research integrity among their members. The data indicate that although many of the societies are working to promote research integrity through ethics codes and activities, they lack rigorous assessment methods to determine the effectiveness of their efforts. An earlier version of this paper was presented at the AAAS-Office of Research Integrity (ORI) meeting in Washington DC on the theme: “The Role and Activities of Scientific Societies in Promoting Research Integrity” held on April 10–11, 2000.     

Research ethics and the principle of Justice as Fairness – A restatement

In my recent article, I addressed the question of whether a potential categorical exclusion of decisionally impaired patients from non-therapeutic medical research would be inaccordance with the Principle of Justice as Fairness. I came to the conclusion that a categorical exclusion of decisionally impaired persons from relevant research projects may collide with Rawls’s understanding of Justice as Fairness. Derek Bell has criticized my paper by denying that it is legitimate to apply Rawls to this bioethical problem. In my restatement I try to show that an extrapolation of John Rawls’s thought to such bioethical cases is possible, because Rawls himself has written that his orientation towards decisionally non-impaired persons is an idealized situation that allows extrapolations. In a second part I try to show that Bell hasroughly misunderstood my concept of “presumed consent” which I make a prerequisite for the legitimisation of research on decisionally impaired persons. In using advance consent as a proposal for resolving the problem, Bell has indirectly confirmed my approach because he is using a similar construct of consent, which operates with similar hypotheses and probabilities of error. I see here no categorical difference between Bell’s conclusion and my discussion. Thus, Bell’s reply does not represent a refutation of my thoughts, but rather it is a para phrased confirmation of my central theses. I conclude by showing the relevance of Rawls, pointing out that the discussion between Bell and me illustrates how Rawls’s concept of reflective equilibrium is an appropriate approach to finding a solution to this bioethical problem. This revised version was published online in June 2006 with corrections to the Cover Date.     

The Emergence of Clinical Research Ethics Consultation: Insights From a National Collaborative

The increasing complexity of human subjects research and its oversight has prompted researchers, as well as institutional review boards (IRBs), to have a forum in which to discuss challenging or novel ethical issues not fully addressed by regulations. Research ethics consultation (REC) services provide such a forum. In this article, we rely on the experiences of a national Research Ethics Consultation Collaborative that collected more than 350 research ethics consultations in a repository and published 18 challenging cases with accompanying ethical commentaries to highlight four contexts in which REC can be a valuable resource. REC assists: 1) investigators before and after the regulatory review; 2) investigators, IRBs, and other research administrators facing challenging and novel ethical issues; 3) IRBs and investigators with the increasing challenges of informed consent and risk/benefit analysis; and 4) in providing flexible and collaborative assistance to overcome study hurdles, mediate conflicts within a team, or directly engage with research participants. Institutions that have established, or plan to establish, REC services should work to raise the visibility of their service and engage in open communication with existing clinical ethics consult services as well as the IRB. While the IRB system remains the foundation for the ethical review of research, REC can be a valuable service for investigators, regulators, and research participants aligned with the goal of supporting ethical research.     

Roles for scientific societies in promoting integrity in publication ethics

Scientific societies can have a powerful influence on the professional lives of scientists. Using this influence, they have a responsibility to make long-term commitments and investments in promoting integrity in publication, just as in other areas of research ethics. Concepts that can inform the thinking and activities of scientific societies with regard to publication ethics are: the “hidden curriculum” (the message of actions rather than formal statements), a fresh look at the components of acting with integrity, deviancy as a normally occurring phenomenon in human society, and the scientific community as an actual community. A society’s first step is to decide what values it will promote, within the framework of present-day standards of good conduct of science and given the society’s history and traditions. The society then must create educational programs that serve members across their careers. Scientific societies must take seriously the implications of the problem; set policies and standards for publication ethics for their members; educate about and enforce the standards; bring the issues before the members early and often; and maintain continuing dialogue with editors. An earlier version of this paper was presented at the AAAS-Office of Research Integrity (ORI) meeting in Washington DC on the theme: “The Role and Activities of Scientific Societies in Promoting Research Integrity” held on April 10–11, 2000.     

On the Limits of Parental Proxy Consent: Children's Right to Non-Participation in Non-Therapeutic Research

This paper considers what are the appropriate limits of parental or guardian proxy consent for a child's participation in medical or social science research. Such proxy consent, it is proposed, is invalid in regards “non-therapeutic research.” The latter research may add to scientific knowledge and/or benefit others, but any benefit to the child research participant is but a coincidental theoretical possibility and not a primary objective. Research involving children, without intended and acceptable prospect of beneficial outcome to the individual participant, even if with negligible risk, does not meet the test for “best interests.” Proxy consent for children's involvement in research is justifiable only when given for and on behalf of the child in his or her best interest to enhance the child's well-being. Only in the latter case is the parental proxy consent situation analogous in regards key criteria to a competent individual consenting to research participation. This revised version was published online in August 2006 with corrections to the Cover Date.     

Placebos and the UK medical research council — and the consumer perspective

The UK Medical Research Council, in order to further its mission of maintaining and improving human health, supports a substantial number of clinical trials on a wide variety of medical questions; some of these trials involve the use of placebos as controls or to maintain blinding. Before providing support, proposed trials are carefully reviewed to assess scientific quality, and to determine whether a placebo is required and is ethical — in addition to ethics review by independent Research Ethics Committees. Some questions such as the choice of placebos in trials in developing countries, in surgical trials and those involving alternative medicine require consideration of additional, specific issues. Involvement of consumers in MRC work has been increasing and includes the establishment of a Consumer Liaison Group; members of this group comment on patient information leaflets for clinical trials, helping to improve patient understanding of trials and ensuring topics like placebo use are explained clearly. Views differ on the value of placebos in clinical care and on their mechanism of action; continuing research is helping to clarify the issues. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

The council of Europe’s instruments on biomedical research: how is conflict of interest addressed?

Conflict of interest is an issue that has been put in the spotlight by the commercial application of the new biomedical technologies. This paper presents the approach of the Council of Europe and the binding legal instruments to deal with this problem. The main focus is on the Convention on Human Rights and Biomedicine, and its draft additional Protocol on Biomedical Research. An earlier version of this paper was presented at an International Conference on “Conflict of Interest and its Significance in Science and Medicine” held in Warsaw, Poland on 5–6 April, 2002. The views expressed are personal and do not necessarily reflect any official position of the Council of Europe.     

Beyond conflict of interest: the responsible conduct of research

This paper reports data and scholarly opinion that support the perception of systemic flaws in the management of scientific professions and the research enterprise; explores the responsibility that professional status places on the scientific professions, and elaborates the concept of the responsible conduct of research (RCR). Data are presented on research misconduct, availability of research guidelines, and perceived research quality. An earlier version of this paper was presented at an International Conference on “Conflict of Interest and its Significance in Science and Medicine” held in Warsaw, Poland, 5–6 April, 2002. The opinions expressed herein are those of the author and do not necessarily represent the views of the Office of Research Integrity, the U.S. Department of Health and Human Services, or any other federal agency.     

American college of epidemiology ethics guidelines: Foundations and dissemination

Epidemiology is a core science of public health, focusing on research related to the distribution and determinants of both positive and adverse health states and events and on application of knowledge gained to improve public health. The American College of Epidemiology (ACE) is a professional organization devoted to the professional practice of epidemiology. As part of that commitment, and in response to concerns for more explicit attention to core values and duties of epidemiologists in light of emerging issues and increased scrutiny of epidemiology, the College developed, adopted, and published a set of Ethics Guidelines. The structure of the ACE ethics guidelines is in four parts: (1) a brief statement of core values and duties of epidemiologists, coupled with the virtues important to professional practice; (2) concise statements of key duties and obligations; (3) exposition of the duties and obligations with more applications; and (4) a brief summary and conclusion. The Guidelines have been published on the ACE website and in the official College journal Annals of Epidemiology. The guidelines contain (and maintain) core elements that define the discipline of epidemiology and its fundamental duties, but they are also intended to be dynamic and evolving, responsive to a changing professional and social environment. An earlier version of this paper was presented at the AAAS-Office of Research Integrity (ORI) meeting in Washington DC on the theme: “The Role and Activities of Scientific Societies in Promoting Research Integrity” held on April 10–11, 2000. Affiliations of co-authors: Douglas L. Weed, MD, MPH, PhD is Director of the Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute; Jeffrey P. Kahn, PhD, MPH, is Professor of Medicine and Director of the Center for Bioethics, UMN Twin Cities, Minneapolis; Michael A. Stoto, PhD, is Associate Director for Public Health, RAND Center for Domestic and International Health Security, Arlington, VA.     

The Ethics Trapeze

This article constitutes the introduction to a collection of essays in volume 4 of JAE, representing an extremely diverse collection of pieces written by authors from equally diverse backgrounds with the purpose of sharing the theoretical and practical issues related to research-ethics, or on ethics more generally. All of the articles are fresh contributions to the research-ethics review debate. The 17 authors of the 12 articles come from the United States, South Africa, and Canada. Their disciplinary or research backgrounds include Aboriginal literatures, English literature, English-as-a Second-Language pedagogy, French literature, history, language and literacy, liberal arts, and linguistics – all fields in the cluster of the humanities. The volume also has contributions from social work, sociology, and speech pathology. The world of research-ethics review has become so pervasive that it invades all areas of research: it does not respect disciplinary boundaries. The articles in this special volume represent, in short, a microscope of the research world.     

Action research,emancipation and design thinking

This article evaluates the notion and practice of action research, as defined by contributors to the recent special issue ‘Action Research and Emancipation’ in this journal. The author argues that, although action research implicitly has a design orientation, it largely draws on the humanities and sciences as its main role models. As a result, action researchers nowadays do not see themselves as design professionals. Idealized design methods serve to illustrate how design research can help realize the emancipatory intentions of action researchers. Copyright © 2004 John Wiley & Sons, Ltd.     

Ethics education in science and engineering: The case of animal research

Conclusion The past one hundred fifty years of debate over the use of animals in research and testing has been characterized mainly byad hominem attacks and on uncritical rejection of the other sides’ arguments. In the classroom, it is important to avoid repeating exercises in public relations and to demand sound scholarship. This paper is a modification of material originally included in the handbook which accompanied the American Association for the Advancement of Science (AAAS) Seminar “Teaching Ethics in Science and Engineering”, 10–11 February 1993.     

Influences of Creative Personality and Working Environment on the Research Productivity of Business School Faculty

Previous research on creative working environments has focused on business organizations. This study examined the influence of creative personality and creative working environment on the research productivity of business faculty. It was hypothesized that creative personality, family support, colleague support, research resources, and workload pressures would all have a positive association with research productivity. Management faculty people (N = 247) employed in business schools with a doctoral program participated in an online survey. Research productivity was assessed using both objective counts of journal publications across a 5-year period and self-report. Support from colleagues and workload pressures were positively associated with total self-reported publications. Research resources and workload pressures were positivly associated with publications in top management journals. Implications for future research and practice are discussed.     

Group mentoring to foster the responsible conduct of research

This article reports on a method of group mentoring to strengthen responsible research conduct. A key feature of this approach is joint exploration of the issues by trainees and their faculty research supervisors. These interactions not only help participants learn about current ethical norms for research practice, but also draw on the accumulated experience of faculty and staff about practical problems of research conduct, and help to make faculty more articulate about responsible research conduct and so better able to guide their trainees. By working with departments or laboratories as a whole the method facilitates the formulation of specific norms appropriate to particular research situations and to strengthen the group’s ability to support appropriate behavior and deal with new issues as they arise. It also gives students more ways to ask questions about research practice and to benefit from the experience of all members of their department or group as well as their own research supervisors. The method is well tested and has been well received by a wide variety of departments and research groups. It provides the means for a constructive and enjoyable response to the Public Health Service’s (PHS) new Policy on Instruction in the Responsible Conduct of Research (RCR) that requires education in the responsible conduct of research for all those funded by PHS funds, including faculty and staff as well as trainees. An earlier version of this paper was presented at a National Science Foundation sponsored conference on Mentoring and Research Values: Students as Vital Human Resources, Chicago, IL, USA, March 1995.     

Placebo: Its action and place in health research today

The place for the placebo in human clinical research is addressed in this paper. The World Medical Association which is comprised of some 80 National Medical Associations uses much of its resources to address medical ethics and human rights issues. It adopted the Declaration of Helsinki in June 1964 which addressed the protection of individuals in clinical trials. The use of placebos assumes an important role in this document. Five Revisions of the Declaration of Helsinki have occurred and the most recent was adopted in October 2000. The provisions on placebo are now in Paragraph 29 which reads as follows: “The benefit, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic methods exists.” The reactions to the newly revised version of the Declaration of Helsinki were numerous and rapid, not the least of which was the paragraph I quoted above. At the direction of the WMA Council, a small group of experts together with the WMA workgroup studied the Paragraph 29 to ensure that no ethically sound research was being restricted by the revision. The outcome was approved by the Council and later the WMA General Assembly in October 2000. This gives a note of clarification as to the appropriate use of placebos. Numerous papers and statements over the last several years have described positions very much in line with the Note of Clarification cited above. This paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

Human and Animal Subjects of Research: The Moral Significance of Respect versus Welfare

Human beings with diminished decision-making capacities are usually thought to require greater protections from the potential harms of research than fully autonomous persons. Animal subjects of research receive lesser protections than any human beings regardless of decision-making capacity. Paradoxically, however, it is precisely animals’ lack of some characteristic human capacities that is commonly invoked to justify using them for human purposes. In other words, for humans lesser capacities correspond to greater protections but for animals the opposite is true. Without explicit justification, it is not clear why or whether this should be the case. Ethics regulations guiding human subject research include principles such as respect for persons—and related duties—that are required as a matter of justice while regulations guiding animal subject research attend only to highly circumscribed considerations of welfare. Further, the regulations guiding research on animals discount any consideration of animal welfare relative to comparable human welfare. This paper explores two of the most promising justifications for these differences␣between the two sets of regulations. The first potential justification points to lesser moral status for animals on the basis of their lesser capacities. The second potential justification relies on a claim about the permissibility of moral partiality as␣found in common morality. While neither potential justification is sufficient to justify the regulatory difference as it stands, there is possible common ground between supporters of some regulatory difference and those rejecting the current difference.