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Introduction: Vulnerability in
First-in-Human Trial Participants:
Vulnerability
in Biomedical
The 21st-century translational science campaign could Vulnerability as a Regulatory Category
Research
lead to an increase in first-in-human (FIH) trials. As tests in Human Subject Research
of investigational interventions move from the labora-tory to human research, scientists, officials, and review committees should address ongoing concerns about the ethics of FIH trials. In this article, I describe three ethical This article examines and critiques the use of the term considerations relevant to all FIH trials: (1) the require- “vulnerability” in U.S. and international regulations and ment for adequate preclinical research; (2) study design guidelines on research ethics. After concluding that the safeguards; and (3) choice of subject population. I also term is currently used in multiple, often inconsistent, examine specific ethical considerations relevant to the senses, it calls on regulators to differentiate between three three subject populations (healthy volunteers, seriously ill distinct types of vulnerability: “consent-based vulnerabil- patients lacking standard treatment options, and stable ity,” “risk-based vulnerability,” and “justice-based vulner- patients) involved in FIH research. I recommend a variety of actions that could increase subject protection and the value of the information generated in FIH trials. Vulnerability in Research: Individuals
The Vulnerability of the Very Sick
When seriously ill patients for whom existing treatments Individuals with limited resources are often presumed to are inadequate are invited to participate in clinical trials be vulnerable in research. Concerns include the possibil- that offer a new treatment, should those persons be con- ity of impaired decision making, susceptibility to undue sidered “vulnerable”? And if so, what additional protec- inducement, and risk of exploitation. Although each of tions should they be accorded? This article attempts to these concerns should be considered by investigators and IRBs, none justifies categorical exclusion of individuals with limited resources. Vulnerability in Clinical Research with
Patients in Pain: A Risk Analysis
Limited English Proficiency and
Disparities in Clinical Research
Some have characterized patients living with intractable pain as a vulnerable population in both clinical and Patients with Limited English Proficiency (LEP) are a research settings. Labeling the population as vulnerable, protected class under the Civil Rights Act. However, clini- however, does not provide clarity regarding the potential cal trials continue to remain largely inaccessible to this risks that they face when they participate in research. population. This article lays out the scientific, legal, and Instead, research vulnerability for patients in pain is a ethical rationales for the inclusion of LEP subjects in clini- function of an interaction between their pain conditions and elements of the research enterprise. Therefore, the identification of potential risks requires consideration not only of characteristics of patients with chronic pain, but also consideration of features of researchers, the quality of institutional oversight, and the medical/social environ-ment within which the research is conducted. This paper provides an analysis of those risks and provides some sug-gestions as to how the risks might be better managed.
vulnerability in biomedical research • spring 2009 It also addresses broader questions of potential for stigma Vulnerable Brains: Research Ethics and
and risk to individuals and communities. The article concludes that the research should be permitted legally because either it does not involve human subjects, or it satisfies the requirements for waiver of consent; and that Seven specific challenges in patient vulnerability related to the research should also be permitted because the ethical neurosurgical advancement highlight needed augmenta- principal of avoiding harm to individuals is fully satis- tions for standards in innovation and research that do not fied based on a careful reading of the lessons of the tissue unduly inhibit access to potential therapies while assuring bank, biological property rights, and blinded seropreva- lence study debates, as well as a consideration of other potential harms that might be involved.
iPLEDGE Allegiance to the Pill:
In Defense of Bioethics
Toby L. Schonfeld, N. Jean Amoura, and Although bioethics societies are developing standards for clinical ethicists and a code of ethics, they have been The United States Food and Drug Administration (FDA), castigated in this journal as “a moral, if not an ethics, in collaboration with pharmaceutical manufacturers, have disaster” for not having completed this task. Compared recently implemented a heavily revised risk-management with the development of codes of ethics and educational program for patients on isotretinoin (Accutane), a drug standards in law and medicine, however, the pace of pro- with known and pronounced teratogenic effects. This fessionalization in bioethics appears appropriate. Assessed revised risk management plan places significant burdens by this metric, none of the charges leveled against bioeth- on both providers and patients in the hopes of achiev- ics are justified. The specific charges leveled against the ing its goal of reducing fetal exposure to isotretinoin. American Society for Bioethics and Humanities (ASBH) The main focus of this paper is to discuss the burdens of and its Core Competencies report are analyzed and reject- various aspects of the program in relationship to poten- ed as artifacts of an ahistoric conception of the stages by tial corresponding benefits. In particular, we evaluate which organizations professionalize. For example, the the pregnancy rates of women on isotretinoin therapy charge that the ASBH should provide definitive criteria for compared with that of the general population and the what counts as “medical ethics consultation” antecedent rate changes based on the risk management programs. to further progress towards professionalization is assessed Additionally, we investigate whether the benefits of the by comparing it with the American Medical Association’s program for women have increased as the benefits have decades-long struggle to define who can legitimately claim risen. We devote special attention to the ethical implica- the title “medical doctor.” Historically, clarity about who is tions of the intent of the program and to an analysis of the legitimately a doctor, a lawyer — or a “clinical ethicist” — ethical justification of the restrictions placed on women of is a byproduct of, and never antecedent to, the decades– childbearing potential (WCP) as it compares to the risk- long process by which a field professionalizes. The charges benefit relationship of using isotretinoin.
leveled against ASBH thus appear to be a function of impatient, ahistoric perfectionism. Prejudice and the Medical Profession:
A Walk in the Park: A Case Study
Zita Lazzarini, Patricia Case, and Over the past decades the mortality rate in the United States has decreased, and life expectancy has increased. Yet a number of recent studies have drawn Americans’ Can researchers, interested in novel ways to assess HIV attention to the fact that racial and ethnic disparities seroprevalence among populations which are otherwise persist in health care. It is clear that the U.S. health care hidden, collect condoms that have been discarded on the system, which is the envy of the world, is not only flawed ground in a public sex environment and test them for by basic injustices, but may be the cause of both injury HIV? Researchers, who use other types of abandoned and death for members of racial and ethnic minorities. samples, such as discarded syringes, hair or saliva sam- Progress has been made in several areas since the original ples, or excess biological samples, confront similar issues. Institute of Medicine 2002 report. However, five years This review evaluates whether such abandoned tissues can later, the 2007 National Healthcare Disparities Report be studied based on U.S. Code of Federal Regulations and (NHDR) reported that overall, disparities in quality and literature on related issues including: research involving access for minority groups and poor populations have banked tissues, blinded seroprevalence studies, and prop- not been reduced since the original report. The three key erty claims that individuals might make on the samples. themes that have emerged from this report are the fol- lowing: (1) overall, disparities in health care quality and Symposium
access are not getting smaller; (2) progress is being made, articles are
but many of the biggest gaps in quality and access have not been reduced; and (3) the problem of persistent uninsur- ance is a major barrier to reducing disparities. Unless mea- sures are taken to address this racism, unless a new sense of trust is established between the medical establishment and racial and ethnic minorities, these injustices will con- tinue to deepen and expand, and more lives will be placed in jeopardy. What is needed is a comprehensive, multi-lev- el, culturally relevant strategy that contains interventions that target individuals, communities, and the nation as a whole. This will entail understanding the causes of racism in the medical profession, identifying practical interven- tions that address racism in individuals, communities, and the nation as a whole, and forming partnerships that will work to develop a new sense of trust between the medical establishment and the minority communities. Independent
articles are essays
Currents in Contemporary Ethics
unrelated to the symposium topic, subjects within the larger medical Teaching Health Law
Reviews in Medical Ethics
Columns are
written or edited by leaders in their fields and appear in each issue of Recent Developments in Health Law
Harvard Law and Health Care Society Pharmaceutical
Index to Volume 36
Regulations
Calendar of Events
vulnerability in biomedical research • spring 2009

Source: http://www.aslme.org/media/downloadable/files/links/t/o/toc37_1.pdf