Disclosure Issues in Neuroscience Research

Issues of disclosure arise in neuroscientific research during the informed consent process, whenever incidental findings are identified, and when study results are generated. The possibility of disclosure of incidental findings and/or research results may raise informational expectations on the part of subjects and may alter a study's risk:benefit ratio. We recommend that the informed consent process address this potential consequence of research participation, and specify the conditions under which particular types of information will be offered, the conditions under which information may not be disclosed, and any provisions for helping subjects make sense of the information to be disclosed.     

Disclosing Conflicts of Interest to Research Subjects: An Ethical and Legal Analysis

In this article, I examine the ethical and legal issues related to disclosure of conflicts of interest to research subjects, and discuss some empirical studies related to the topic. I argue that researchers have an ethical obligation to disclose conflicts of interest to research subjects, provided that they take steps to help subjects understand information about conflicts of interest and how to interpret it. Researchers also may have a legal duty to disclose conflicts of interests to subjects, depending on the facts of the case and the court's interpretation of the law. To reinforce and clarify the legal obligation to disclose conflicts of interest, the federal regulations should be amended to include disclosure of conflicts of interest as one of the informed consent requirements. Institutional review boards play a key role in helping researchers to disclose conflicts of interests to subjects in an appropriate manner. Institutional review boards should approve the disclosure language in informed consent documents, and they should require researchers to disclose financial interests to research subjects, if they have any, as a condition of approval.     

Disclosing conflicts of interest to research subjects: an ethical and legal analysis

In this article, I examine the ethical and legal issues related to disclosure of conflicts of interest to research subjects, and discuss some empirical studies related to the topic. I argue that researchers have an ethical obligation to disclose conflicts of interest to research subjects, provided that they take steps to help subjects understand information about conflicts of interest and how to interpret it. Researchers also may have a legal duty to disclose conflicts of interests to subjects, depending on the facts of the case and the court's interpretation of the law. To reinforce and clarify the legal obligation to disclose conflicts of interest, the federal regulations should be amended to include disclosure of conflicts of interest as one of the informed consent requirements. Institutional review boards play a key role in helping researchers to disclose conflicts of interest to subjects in an appropriate manner. Institutional review boards should approve the disclosure language in informed consent documents, and they should require researchers to disclose financial interests to research subjects, if they have any, as a condition of approval.     

Disclosure issues in neuroscience research

Issues of disclosure arise in neuroscientific research during the informed consent process, whenever incidental findings are identified, and when study results are generated. The possibility of disclosure of incidental findings and/or research results may raise informational expectations on the part of subjects and may alter a study's risk:benefit ratio. We recommend that the informed consent process address this potential consequence of research participation, and specify the conditions under which particular types of information will be offered, the conditions under which information may not be disclosed, and any provisions for helping subjects make sense of the information to be disclosed.     

Informed Consent of Very Sick Subjects in Nigeria

This article highlights a number of ethical challenges I face in obtaining informed consent from very sick subjects with suspected pulmonary tuberculosis (TB). Some of the subjects with TB have an associated human immunodeficiency virus (HIV) infection. From my experience in administering informed consent and health surveys, I found the subjects to be generally mentally stable but physically exhausted. Many of the very sick subjects cough excessively and cannot tolerate a 45-minute conversation with the study staff in order for them to administer consent and conduct a survey after the routine clinical evaluation. In this situation, the administration of a qualitative consent that preserves the subject's right and autonomy becomes a challenge.     

Informed consent comprehension among vulnerable populations in Ecuador: video-delivered vs. in-person standard method

The informed consent comprehension process is key to engaging potential research subject participation. The aim of this study is to compare informed consent comprehension between two methods: standard and video-delivered. We compared the in-person and video-delivered informed consent process in the Familias Unidas intervention. We evaluated comprehension using a 7-item true/false questionnaire. There were a total of 152 participants in the control group and 87 in the experimental. General characteristics were similar between both groups (p > 0.05). First-attempt informed consent comprehension was higher in the intervention group but was not statistically significant (80% and 78% respectively p = 0.44). A video-delivered informed consent process did not differ from the standard method of informed consent in a low educational and socioeconomic environment.     

Informed consent of very sick subjects in Nigeria

This article highlights a number of ethical challenges I face in obtaining informed consent from very sick subjects with suspected pulmonary tuberculosis (TB). Some of the subjects with TB have an associated human immunodeficiency virus (HIV) infection. From my experience in administering informed consent and health surveys, I found the subjects to be generally mentally stable but physically exhausted. Many of the very sick subjects cough excessively and cannot tolerate a 45-minute conversation with the study staff in order for them to administer consent and conduct a survey after the routine clinical evaluation. In this situation, the administration of a qualitative consent that preserves the subject's right and autonomy becomes a challenge.     

Anticipated Ethics and Regulatory Challenges in PCORnet: The National Patient-Centered Clinical Research Network

PCORnet, the National Patient-Centered Clinical Research Network, seeks to establish a robust national health data network for patient-centered comparative effectiveness research. This article reports the results of a PCORnet survey designed to identify the ethics and regulatory challenges anticipated in network implementation. A 12-item online survey was developed by leadership of the PCORnet Ethics and Regulatory Task Force; responses were collected from the 29 PCORnet networks. The most pressing ethics issues identified related to informed consent, patient engagement, privacy and confidentiality, and data sharing. High priority regulatory issues included IRB coordination, privacy and confidentiality, informed consent, and data sharing. Over 150 IRBs and five different approaches to managing multisite IRB review were identified within PCORnet. Further empirical and scholarly work, as well as practical and policy guidance, is essential if important initiatives that rely on comparative effectiveness research are to move forward.     

Ethics of research design

Discussions of ethical issues in research involving human subjects most usually provoke concerns about valid informed consent procedures. However, considering the recognized limitations of informed consent, arguably the way a study is designed is a more consequential concern for subject well‐being. This paper summarizes ethical issues in the design of clinical research, with reference to historic and current guidelines. Special attention is given to randomized clinical trials (RCTs) and psychiatric research.     

Resolving Beecher's Paradox: Getting beyond IRB reform

Protection of persons participating as research subjects is an essential element of ethical research conduct. There is growing concern that the existing system of institutional review boards (IRBs) and informed consent may not be adequate and is in need of reform. When science and medicine are “merged”; in clinical research, confusion of roles and conflicts of interests arise in relationships between patient‐subjects and physician‐investigators. IRBs have always had a primary role in protection of research participants. Their efforts to protect research subjects may make it more difficult for investigators to conduct research. This tension has lead to the development of an adversarial relationship between IRBs and investigators. Investigators and IRBs are also subject to external pressures that could impact efforts to protect research subjects. Efforts are underway to address these concerns. IRB reform, while needed, is not likely to be sufficient. Adoption of a new paradigm in which IRBs, investigators and research sponsors collectively accept protection of research subjects as their primary and shared responsibility may provide a more effective and efficient model that will be better able to deal with difficult ethical and social issues in clinical research.     

The therapeutic misconception,beneficence, and respect

In order to provide benefits to society, human medical trials must place subjects at risk of harm. This activity is thought to be justified in part by the consent of the subjects involved. But, studies have shown that most such consents are based on a therapeutic misconception (TM); the false belief of subjects that their researchers will act as their personal physicians (seeking their benefit and protecting them from harm), rather than placing them at risk of harm for the good of others. Toleration by researchers of the TM in their subjects is a form of “informational manipulation”; that renders consent procedures disrespectful to subject autonomy. Consent obtained from subjects who labor under a TM is neither voluntary nor informed; as long as they have not been disabused of the TM, the action they take in enrolling in a trial is not the one they intend nor is it autonomously chosen. Changes in consent procedures should be adopted to ensure that all subjects are aware inter alia that (a) the health interests of future patients (as well as the researchers’ and their sponsors’ financial interests) may be more important to researchers than the interest of a subject in his or her health, and (b) normal subjects neither understand nor believe this when told. Close attention to the response of prospective subjects to this information should allow for the exclusion of all but the truly altruistic. However, the result of conscientious implementation of such policies would likely be that human medical research could no longer be conducted on more than a minimal level.     

EXCLUDING PARTICULAR INFORMATION FROM CONSENT FORMS

Although the informed consent process is crucial to protecting human research subjects, there are cases when particular information within the consent form may present risks to those subjects. In this paper, we examine a case in which including the sponsor’s name on the consent form may allow the form to serve as a surrogate for subjects’ HIV status.

There is no literature addressing the ethical acceptability of excluding particular information from consent forms, and there exists little regulatory guidance on this issue. We argue that excluding information from the consent form is, in fact, obligatory when that information is disclosed orally during the consent process but its presence on the form poses risks to the subjects the consent process is designed to protect. Further, we argue that the regulations ought to be amended to reflect this obligation.     

Scientific evidence and the judicial system

Research involving the vulnerable sick raises difficult challenges for investigators and Institutional Review Boards. Exactly who among the ill counts as vulnerable is a matter of judgement, and involves consideration of susceptibility to harm and capacity to provide free and informed consent. A balanced approach is required when protections are considered, and the benefits as well as the risks of research participation must be carefully weighed. A variety of protections for the vulnerable sick in research are available, including enrolling subjects in a study only with a strong justification, ensuring that consent is free and comprehending, and setting limits on the risk to which they may be asked to endure. Discussion of three contemporary controversies, placebo‐controlled trials in the psychiatric setting, phase I clinical trials and oncology patients, and emergency room research involving patients incapable of giving consent, highlights the little recognized prominence of risk‐benefit issues in the clinical studies in the vulnerable sick.     

Perceptions of Academic Health Science Research Center Personnel Regarding Informed Consent Processes and Therapeutic Misconception

Introduction: Instrumentation exists to measure voluntariness and misunderstanding in informed consent processes. However, research personnel’s perspectives about using instrumentation to measure therapeutic misconceptions in research participants has not been reported. We designed a workshop to promote research personnel knowledge of emerging instrumentation and to study the perceptions of research personnel regarding such instruments.

Methods and Findings: Two nationally recognized experts who have developed psychometric instruments to measure aspects of informed consent presented their recent findings to research personnel of the Medical University of South Carolina at a one-day workshop. Following the presentations, workshop attendees divided into two focus groups and shared their perceptions regarding the presentation content. Inductive thematic analysis detected themes related to informed consent processes including: investigator/provider role clarity; investigator transparency; therapeutic misconception; and screening subjects for understanding.

Conclusion: Our findings suggest future directions in applied, proactive empirical research to better understand investigator perceptions and practices related to transparency in research, and to develop instrumentation to detect risks to the integrity of informed consent in order to promote voluntariness and autonomy and minimize therapeutic misconception in research practices.     

Informed Consent and Investigational New Drug Abuses in the U.S. Military

Objective: The focal point of this investigation was to research the ethical issues surrounding the military's requests for informed consent waivers when using investigational drugs, and the recent debate surrounding the anthrax vaccine as an investigational new drug (IND). Design: The military's management of the informed consent process was examined using documents obtained through the Freedom of Information Act, Institutional Review Board (IRB) minutes, consent forms, legal pleadings, and protocols for specific investigational drugs. Results: In December 1990, prior to Operation Desert Storm, the Federal Drug Administration (FDA) granted the Department of Defense (DoD) an unprecedented waiver to the federally mandated informed-consent requirement for the use of investigational drugs. However, the waiver approval was conditional, and the FDA insisted on several safeguards. Partially in response to the subsequent Gulf War Syndrome debate, the FDA recently evaluated the military's use of investigational drugs during the Gulf War. The FDA cited the military for significant deviations from the originally approved protocols. Most notably, the military was found to be abusing the IRB process by convening a second IRB when the first IRB concluded that waiving informed consent was unethical. In addition, there was a gross lack of documentation and no monitoring of adverse reactions. The DoD's plan to use the current anthrax vaccine on all 2.4 million troops against inhalation anthrax has kindled an additional investigational drug controversy. The safety and efficacy of the use of the anthrax vaccine as a prophylactic against inhalation anthrax have been questioned by both military and medical organizations. There have never been any published studies of human efficacy or long-term effects for the anthrax vaccine. In addition, the military is not using the vaccine for its intended purpose, and it is also not adhering to prescribed dosing schedules. There is clear evidence to support the claim that, in fact, the military's use of the anthrax vaccine should be considered experimental. Conclusions: I argue that in medical situations, the military is obligated to treat its troops as autonomous persons entitled to basic rights and protections. The DoD is currently using an approved drug, the anthrax vaccine, for an unapproved purpose and in an unapproved manner. In doing so, the DoD is not only violating the FDA's regulations against such practices, it is also violating an executive order which only allows the president to authorize the use of INDs on service members without their consent.     

A method for considering the acceptability of novel biotechnologies for the control of brushtail possums

Abstract

Public acceptance and regulatory approval of biotechnologies is increasingly dependent on consideration of cultural, ethical and spiritual effects, and the opportunity for community involvement. The objective of this study was to articulate a means for researchers to identify relevant issues during the development of the technologies. It encompassed the substantive issues, such as safety, the provision of credible and adequate public information, and the opportunity for citizens, as well as stakeholders, to give society's informed consent. In this initial analysis of novel toxins and infertility or sterility-inducing agents being developed to manage pest populations of brushtail possums, several issues were identified. They included the risk associated with fertility controls entering the food chain, the severity of animal welfare compromise with toxins, and the adequacy of terminology used to describe pest control agents. This approach provides a means for researchers to acknowledge the issues contributing to public acceptance of biotechnologies during their development and with the involvement of those with interests in biotechnology.     

The therapeutic misconception,beneficence, and respect

In order to provide benefits to society, human medical trials must place subjects at risk of harm. This activity is thought to be justified in part by the consent of the subjects involved. But, studies have shown that most such consents are based on a therapeutic misconception (TM); the false belief of subjects that their researchers will act as their personal physicians (seeking their benefit and protecting them from harm), rather than placing them at risk of harm for the good of others. Toleration by researchers of the TM in their subjects is a form of "informational manipulation" that renders consent procedures disrespectful to subject autonomy. Consent obtained from subjects who labor under a TM is neither voluntary nor informed; as long as they have not been disabused of the TM, the action they take in enrolling in a trial is not the one they intend nor is it autonomously chosen. Changes in consent procedures should be adopted to ensure that all subjects are aware inter alia that (a) the health interests of future patients (as well as the researchers' and their sponsors' financial interests) may be more important to researchers than the interest of a subject in his or her health, and (b) normal subjects neither understand nor believe this when told. Close attention to the response of prospective subjects to this information should allow for the exclusion of all but the truly altruistic. However, the result of conscientious implementation of such policies would likely be that human medical research could no longer be conducted on more than a minimal level.     

Informed consent for research on stored blood and tissue samples: a survey of institutional review board practices

Numerous position papers have outlined informed consent recommendations for the collection, storage, and future use of biological samples; however, there currently is no consensus regarding what kinds of information should be included in consent forms. This study aimed to determine whether institutional review boards (IRBs) vary in their informed consent requirements for research on stored biological samples, and whether any variation observed could be correlated to factors such as volume of work, IRB members' familiarity with ethical issues in genetic research, and IRBs' use of either of two policy guidelines as resources. A brief survey was mailed to all IRB chairpersons on a mailing list obtained from the Office for Human Research Protections. Survey questions included whether consent forms for the collection of biological samples for future use address each of six provisions recommended in current guidelines and position statements, and whether IRBs used the Office for Protection from Research Risks' 1993 Protecting Human Research Subjects: Institutional Review Board Guidebook, chapter 5 (hereinafter IRB Guidebook) or the National Bioethics Advisory Commission's 1999 Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, Volume I (hereinafter Report) in their deliberations. Despite a low response rate (22%, 427 respondents), results indicate that IRB practices vary substantially. The degree to which the provisions were included in consent forms was found to correlate positively with IRBs that review a greater volume of protocols annually, those that use the National Bioethics Advisory Commission Report in their deliberations, and those that draw on both the Report and the IRB Guidebook.     

Working Group on Ethical Considerations in Science and Scholarship∗

Persons can be subject to involuntary treatment for mental illness or substance abuse in a variety of circumstances. The ability of such persons to give a valid informed consent for research often has been called into question, because the coercive nature of the treatment is thought to impair the voluntariness of their decision making. A careful consideration of the nature of coercion from a “moralized”; perspective focuses attention on two elements that determine the acceptability of consent: the fairness of the proposal to which consent is sought, and the moral baseline from which the proposal is made. Even when coercion is not present, disproportionate rewards offered for participation in research can impair the voluntariness of consent, as can the unintended effects of the social structure of the system in which the research is taking place. When coercion, defined as a moralized concept, is not present, however, and other conditions do not substantially impair voluntariness, consent to research legitimately may be sought from involuntarily treated populations.     

Reflexive Research Ethics in Fetal Tissue Xenotransplantation Research

For biomedical research in which the only involvement of the human subject is the provision of tissue or organ samples, a blanket consent, i.e., consent to use the tissue for anything researchers wish to do, is considered by many to be adequate for legal and Institutional Review Board (IRB) requirements. Alternatively, a detailed informed consent provides patients or study participants with more thorough information about the research topic. We document here the beliefs and opinions of the research staff on informed consent and the discussion-based reflexive research ethics process that we employed in our fetal tissue xenotransplantion research on the impact of environmental exposures on fetal development. Reflexive research ethics entails the continued adjustment of research practice according to relational and reflexive understandings of what might be beneficent or harmful. Such reflexivity is not solely an individual endeavor, but rather a collective relationship between all actors in the research process.