Evolution of universal review and disclosure of MRI reports to research participants.

BACKGROUND: Although incidental findings (IF) are commonly encountered in neuroimaging research, there is no consensus regarding what to do with them. Whether researchers are obligated to review scans for IF, or if such findings should be disclosed to research participants at all, is controversial. Objective data are required to inform reasonable research policy; unfortunately, such data are lacking in the published literature. This manuscript summarizes the development of a radiology review and disclosure system in place at a neuroimaging research institute and its impact on key stakeholders. METHODS: The evolution of a universal radiology review system is described, from inception to its current status. Financial information is reviewed, and stakeholder impact is characterized through surveys and interviews. RESULTS: Consistent with prior reports, 34% of research participants had an incidental finding identified, of which 2.5% required urgent medical attention. A total of 87% of research participants wanted their magnetic resonance imaging (MRI) results regardless of clinical significance and 91% considered getting an MRI report a benefit of study participation. A total of 63% of participants who were encouraged to see a doctor about their incidental finding actually followed up with a physician. Reasons provided for not following-up included already knowing the finding existed (14%), not being able to afford seeing a physician (29%), or being reassured after speaking with the institute's Medical Director (43%). Of those participants who followed the recommendation to see a physician, nine (38%) required further diagnostic testing. No participants, including those who pursued further testing, regretted receiving their MRI report, although two participants expressed concern about the excessive personal cost. The current cost of the radiology review system is about $23 per scan. CONCLUSIONS: It is possible to provide universal radiology review of research scans through a system that is cost-effective, minimizes investigator burden, and does not overwhelm local healthcare resources.

The ethical challenges of animal research.

In 1966, Henry K. Beecher published an article entitled "Ethics and Clinical Research" in the New England Journal of Medicine, which cited examples of ethically problematic human research. His influential paper drew attention to common moral problems such as inadequate attention to informed consent, risks, and efforts to provide ethical justification. Beecher's paper provoked significant advancements in human research policies and practices. In this paper, we use an approach modeled after Beecher's 1966 paper to show that moral problems with animal research are similar to the problems Beecher described for human research. We describe cases that illustrate ethical deficiencies in the conduct of animal research, including inattention to the issue of consent or assent, incomplete surveys of the harms caused by specific protocols, inequitable burdens on research subjects in the absence of benefits to them, and insufficient efforts to provide ethical justification. We provide a set of recommendations to begin to address these deficits.

Stakeholder Opinions And Ethical Perspectives Support Complete Disclosure Of Incidental Findings In MRI Research.

How far does a researcher's responsibility extend when an incidental finding is identified? Balancing pertinent ethical principles such as beneficence, respect for persons, and duty to rescue is not always straightforward, particularly in neuroimaging research where empirical data that might help guide decision-making is lacking. We conducted a systematic survey of perceptions and preferences of 396 investigators, research participants and IRB members at our institution. Using the partial entrustment model as described by Richardson, we argue that our data supports universal reading by a neuroradiologist of all research MRI scans for incidental findings and providing full disclosure to all participants.

Moving beyond the welfare standard of psychological well-being for nonhuman primates: the case of chimpanzees.

Since 1985, the US Animal Welfare Act and Public Health Service policy have required that researchers using nonhuman primates in biomedical and behavioral research develop a plan "for a physical environment adequate to promote the psychological well-being of primates." In pursuing this charge, housing attributes such as social companionship, opportunities to express species-typical behavior, suitable space for expanded locomotor activity, and nonstressful relationships with laboratory personnel are dimensions that have dominated the discussion. Regulators were careful not to direct a specific set of prescriptions (i.e., engineering standards) for the attainment of these goals, but to leave the design of the programs substantially up to "professional judgment" at the local level. Recently, however, the Institute of Medicine, in its path-finding 2011 report on the necessity of chimpanzee use in research, bypassed this flexible and contingent concept, and instead, required as a central precondition that chimpanzees be housed in "ethologically appropriate" environments. In so doing, obligations of ethical treatment of one great ape species were elevated above the needs of some research. The evolution and significance of this change are discussed.

Where are we in the justification of research involving chimpanzees?

On December 15, 2011, the Institute of Medicine (IOM) Committee on the Use of Chimpanzees in Biomedical and Behavioral Research issued a final report commissioned by the National Institutes of Health (NIH). It changed the landscape of discussion about the necessity of using chimpanzees in research. The Committee advanced three principles of scientifically warranted research on chimpanzees, but NIH's statement of task provided inadequate opportunity for the Committee to investigate moral problems and their implications for public policy. The IOM Committee's report is a landmark document, but it has weaknesses in its justificatory framework, largely resulting from the Committee's narrow remit from NIH and IOM. We analyze cases mentioned in the report and argue that numerous central ethical issues are neglected, especially ones of justification. Additionally, we consider whether the principles offered by the Committee could be used as criteria governing the use of other animals in biomedical and behavioral research.

Debriefing and accountability in deceptive research.

Debriefing is a standard ethical requirement for human research involving the use of deception. Little systematic attention, however, has been devoted to explaining the ethical significance of debriefing and the specific ethical functions that it serves. In this article, we develop an account of debriefing as a tool of moral accountability for the prima facie wrong of deception. Specifically, we contend that debriefing should include a responsibility to promote transparency by explaining the deception and its rationale, to provide an apology to subjects for infringing the principle of respect for persons, and to offer subjects an opportunity to withdraw their data. We also present recommendations concerning the discussion of deception in scientific articles reporting the results of research using deception.

What do we really know about conflicts of interest in biomedical research?

RATIONALE: Conflicts of interest in research have long been seen to pose serious threats to the integrity of research. Indeed, the past two decades have revealed increased attention to the possible influence of conflicts of interest as the number of research studies funded by private industry have increased. OBJECTIVES: We review empirical findings directly pertinent to issues concerning financial conflicts of interest in biomedical research, and we provide an overview of the current issues and state of understanding concerning such conflicts in research. METHODS: We searched Medline from January 1992 to January 2002 to locate current studies that have reported primary or secondary empirical data pertaining to conflicts of interest in research. RESULTS: The rate of potential conflicts of interest for researchers appears to be at least 30% in some situations although the accuracy of such a rate is untested, and the rate of disclosure of conflicts of interest is as low as 2%. Furthermore, some evidence exists to indicate that researchers with conflicting interests may indeed offer different professional opinions and judgments than those for whom such conflicts do not exist. The effectiveness of various disclosure and management methods for conflicts of interest is unknown. CONCLUSIONS: We summarize the current empirical literature, concluding that relatively little is known based on such data. We suggest a number of questions that need to be answered by future research, and we offer recommendations for policy makers to consider and evaluate in the future in identifying, revealing, and managing conflicts of interest.

Ethical issues in the use of animals in biomedical and psychopharmocological research.

RATIONALE: The ethical debate concerning the use of animals in biomedical and pharmacological research continues to be replete with misunderstandings about whether animals have moral standing. OBJECTIVES: This article briefly reviews the central ethical positions and their relationship to the basic parameters of research regulation from an international perspective. The issues associated with the validation of animal models will then be discussed. Finally, suggestions for empirical ethics research will be presented. METHODS: Recent literature reviews were accessed and analyzed. RESULTS: This review summarizes the pertinent ethical and research literature. CONCLUSIONS: In summary, regardless of the ethical perspective one favors, there is strong agreement that animals matter morally and that at a minimum their welfare must be considered. This position is reflected in the structure of national regulatory schemes that emphasize the three Rs (replacement, reduction, refinement). Researchers should more actively participate in the discussion by becoming more knowledgeable about the details of the ethical issues. Research with animal models has been problematic in that it has often focused on attempting to produce global models of psychiatric disorders, which suffer from inherent validity problems. Researchers must also become more sophisticated about issues of model validation and the nature of the animals they use.

Participants' understanding of the process of psychological research: debriefing.

In a broad-based study of experiences in psychological research, 65 undergraduates participating in a wide range of psychological experiments were interviewed in depth. Overall findings demonstrated that participants hold varying views, with only 32% of participants characterizing their experiences as completely positive. Participants' descriptions of their debriefing experiences suggest substantial variability in the content, format, and general quality of debriefing practices. Just over 40% of the debriefing experiences were viewed favorably. Positive debriefing experiences were described as including a thorough explanation of the study and detailed information concerning the broader relevance of the experiment to the field of psychology. The most common complaint, characterizing 28.8% of the responses, was that the debriefing was unclear and that insufficient information was provided. Participants' views of psychological research and the discipline of psychology were also elicited. Results are discussed in terms of ethical and methodological implications.

Participants' understanding of the process of psychological research: informed consent.

Sixty-five undergraduates participating in a wide range of psychological research experiments were interviewed in depth about their research experiences and their views on the process of informed consent. Overall, 32% of research experiences were characterized positively and 41% were characterized negatively. One major theme of the negative experiences was that experiments were perceived as too invasive, suggesting incomplete explication of negative aspects of research during the informed consent process. Informed consent experiences were viewed positively 80% of the time. However, most of the participants had a limited view of the purpose of informed consent: less than 20% viewed the process as a decision point. Results suggest a number of common pitfalls to standard informed consent practices that have not generally been recognized. Results are discussed in terms of both ethical and methodological implications. Suggestions for improving the informed consent process are also provided.

Institutional animal care and use committees: a flawed paradigm or work in progress?

In his challenging article, Steneck (1997) criticized the creation of the Institutional Animal Care and Use Committee (IACUC) system established by the 1985 amendments to the Animal Welfare Act. He saw the IACUC review and approval of biomedical and behavioral research with animals as an unnecessary "reassignment" of duties from existing animal care programs to IACUC committees. He argued that the committees are unable to do the work expected of them for basically three reasons: (a) the membership lacks the expertise in matters relevant to animal research and care, (b) there exists an inherent and disabling conflict of interest, and (c) the committee's operational base of authority is alien to academic culture and violates essential aspects of academic freedom. In addition, he found that the system is burdensome, requiring enormous expenditures of time and money that inappropriately diverts resources away from the business of scientific discovery. We dispute several aspects of Steneck's historical account and the coherence of his proposals. We believe his proposals, if followed, would be a step back into a failed past.

Harry F. Harlow and animal research: reflection on the ethical paradox.

With respect to the ethical debate about the treatment of animals in biomedical and behavioral research, Harry F. Harlow represents a paradox. On the one hand, his work on monkey cognition and social development fostered a view of the animals as having rich subjective lives filled with intention and emotion. On the other, he has been criticized for the conduct of research that seemed to ignore the ethical implications of his own discoveries. The basis of this contradiction is discussed and propositions for current research practice are presented.

Gender differences in attitudes toward animal research.

Although gender differences in attitudes toward animal research have been reported in the literature for some time, exploration into the nature of these differences has received less attention. This article examines gender differences in responses to a survey of attitudes toward the use of animals in research. The survey was completed by college students and consisted of items intended to tap different issues related to the animal research debate. Results indicated that women were more likely than men to support tenets of the animal protection movement. Likewise, women were more likely than men to favor increased restrictions on animal use and were more concerned than men about the suffering of research animals. Analysis of item contents suggested that women endorsed items reflecting a general caring for animals, were more willing than men to make personal sacrifices such as giving up meat and medical benefits in an effort to protect animals, and were more likely than men to question the use of animals in research on scientific grounds. Men, on the other hand, tended to emphasize the potential benefits arising from the use of animals in research.

Animals in biomedical research: the undermining effect of the rhetoric of the besieged.

It is correctly asserted that the intensity of the current debate over the use of animals in biomedical research is unprecedented. The extent of expressed animosity and distrust has stunned many researchers. In response, researchers have tended to take a strategic defensive posture, which involves the assertation of several abstract positions that serve to obstruct resolution of the debate. Those abstractions include the notions that the animal protection movement is trivial and purely anti-intellectual in scope, that all science is good (and some especially so), and the belief that an ethical consensus can never really be reached between the parties.

Harry Harlow: Lessons on explanations, ideas, and mentorship.

Harry F. Harlow died on December 6, 1981, in Tucson, Arizona. An examination of the process of his professional contributions reveals an intensely antagonistic attitude toward simplistic explanations of psychological phenomena, and a willingness to entertain experimental ideas born in a wide variety of ways. Harlow exemplified these attitudes by designing often disarmingly simple experiments which served as crucial rejoinders to firmly stated explanatory positions. It is also clear that Harlow considered his own constructions as fair game for this style of direct analysis. As a person, Harlow is pictured as a loyal, laissez faire mentor who desired affection but not academic conformity.