Transcript Ethics in Epidemiologic Research Javier Lopez-Zetina, PhD, MA Associate Professor Department of Health Science California State University, Long Beach.

Ethics in Epidemiologic
Research
Javier Lopez-Zetina, PhD, MA
Associate Professor
Department of Health Science
California State University, Long Beach
Module Outline
1. Overview of the IRB Principles of Beneficence, Justice and
Respect for Persons
2. Overview of specific applications of IRB Principles
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Informed Consent
Confidentiality
Disclosure of risks and benefits
Disclosure of conflict of interest
3. Current ethical dilemmas and controversies
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Shared clinical decision-making
Genetic screening
International ethics and IRB review of international collaboration
Participant observation and community-based participatory
research
• Non federally-funded research: ethical framework
Overview of the IRB Principles of
Beneficence, Justice, and
Respect for Persons
At the conclusion of this topic, the student will be able to:
1. Identify and summarize the three basic ethical principles governing
academic research under IRB oversight. Students will read and
comprehend the basic principles expounded in the Belmont Report.
The Belmont Report is available online at the CSULB IRB website.
2. Explain and cite specific application of the principle of Beneficence in
public health research
3. Recognize specific examples of application of the principle of Justice
in bio-medical and community health research.
4. Summarize basic tenets of the principle “Respect for Persons”,
particularly in the context of community-based research.
Presentation of Invited Speakers
Depending on availability, professional
staff from the California State
University, Long Beach Institutional
Review Board will be invited to provide
a succinct summary of the Board’s
mandate and activities.
Video Presentation
In addition, a short video titled: The Belmont
Report: Basic Ethical Principles and Their
Applications, will be presented to the class
for an extended overview of the IRB
Principles. The video is produced by the
National Library of Medicine for the National
Institutes of Health and the Food and Drug
Administration.
Overview
The Belmont Report, a document developed by
agencies of the U.S. government during the
decade of 1960’s, constitutes the ideological
and theoretical foundation of ethical research
in U.S. academic institutions. U.S. academic
institutions receiving federal funding for
research are obligated to enforce compliance
with these principles. As previously
mentioned, three principles are recognized
as fundamental components of ethical
research. They are briefly summarized as
follows.
The CSULB IRB policy document defines
Beneficence as follows. “Persons are treated in an
ethical manner not only by respecting their
decisions and protecting them from harm, but also
by making efforts to secure their well being. Such
treatment falls under the principle of beneficence.
The term "beneficence" is often understood to
cover acts of kindness or charity that go beyond
strict obligation. In this document, beneficence is
understood in a stronger sense as an obligation.
Two general rules have been formulated as
complementary expressions of beneficent actions
in this sense: (1) do not harm and (2) maximize
possible benefits and minimize possible harms”.
CSULB IRB policy definition. Justice. “Who ought to
receive the benefits of research and bear its burdens?
This is a question of justice, in the sense of "fairness in
distribution" or "what is deserved." An injustice occurs
when some benefit to which a person is entitled is
denied without good reason or when some burden is
imposed unduly. Another way of conceiving the
principle of justice is that equals ought to be treated
equally. It is necessary, then, to explain in what
respects people should be treated equally. There are
several widely accepted formulations of just ways to
distribute burdens and benefits. Each formulation
mentions some relevant property on the basis of which
burdens and benefits should be distributed. These
formulations are (1) to each person an equal share, (2)
to each person according to individual need, (3) to
each person according to individual effort, (4) to each
person according to societal contribution, and (5) to
each person according to merit”.
CSULB IRB policy definition. Respect for
Persons. “Respect for persons incorporates
at least two ethical convictions; first, that
individuals should be treated as autonomous
agents, and second, that persons with
diminished autonomy are entitled to
protection. The principle of respect for
persons thus divides into two separate moral
requirements: the requirement to
acknowledge autonomy and the requirement
to protect those with diminished autonomy”.
Overview of specific applications
of IRB Principles
•
•
•
•
Informed Consent
Confidentiality
Disclosure of risks and benefits
Disclosure of conflict of interest
Learning Objectives
By the end of this section, the student should be able to:
1. Understand how the concept of informed consent is
derived from the three IRB Principles.
2. Describe the concept of informed consent as it ultimately
preserves the integrity and autonomy of the research
subject.
3. Describe the basic components of an Informed Consent
Document.
a. Confidentiality
b. Disclosure of Risks and Benefit
c. Disclosure of Conflict of Interest
4. Recognize the importance of cultural factors (i.e.
language preference) in developing informed consent
documentation.
Overview
Informed Consent and Confidentiality are the most important applications of
the IRB principles. Essentially, this application recognizes long-standing
concerns regarding the need to protect the physical and moral integrity
and autonomy of research subjects. Although well-intentioned, the
research paradigm prior to the development of the concept of informed
consent, basically assumed that the researcher “knew” what was better for
the research participants and that the integrity and autonomy of the
participants needed not be discussed extensively with the research
subjects. The informed consent concept stipulates that detailed
information on potential risks and benefits must be given to the research
subject as part of a decision-making process leading to a well-informed
articulation of the participant’s values and expectations.
Moreover, the protection and active defense of the autonomy and integrity
of the participants is further extended to include safeguards for preserving
confidentiality of the personal and research data obtained from
participants. Two research approaches focusing on confidentiality has
been developed to secure a balance between the ethical concerns of
research and the scientific need for data: confidentiality of data and
anonymity of study results. These applications of confidentiality will be
reviewed as fundamental components of the study cases.
Case Study/Discussion Questions
Vertical transmission of HIV continues to pose
dramatic challenges to clinicians and public
health experts in the U.S. and around the world.
Over the past two decades several research
protocols have been implemented nationally and
internationally with the goal of determining
pharmacologic modalities best suited for the
prevention of HIV vertical transmission. One of
these research protocols, PACTG 1002 was
implemented among U.S. subjects, but was the
subject of ongoing controversy over ethical
issues.
Familiarize yourself with the suggested readings and
answer the following questions:
• Based on your knowledge of clinical trials, draw a simple diagram illustrating the
arms of PACTG 1022 (JAIDS)
• What was the endpoint of PACTG 1022 (JAIDS and Harper’s)
•Search the internet (for example the FDA website) and describe in one paragraph
what an FDA’s “Category C’ trial entails
•What are the clinical features of a current AIDS diagnosis
•Based on the newspaper report and without knowing the details of the natural
history of disease, answer the question: What experimental issues are at stake
when evaluating the efficacy of prophylaxis treatment to prevent vertical
transmission of HIV (Harper’s)
•Describe in one paragraph what might possibly explain that no signed consent
form was found for the study subject (Ms. Hafford), and who died in the course
of the PACTG 1022 study (Harper’s)
•According to the article what are four reasons people participate in clinical trials
(Harper’s)
•PACTG 1022 was modeled after HIVNET 012, how many and what were the arms
of HIVNET 012 (Harper’s)
•Why the experimental design of HIVNET 012 called for not using a placebo
(Harper’s)
•Explain what the purpose of randomization is
•Search the CSULB IRB webpage and report what rules are in place when
encountering AEs (adverse effects) and SAEs (serious adverse effects).
References
Hitti J; Frenkel LM; Stek AM; Nachman SA;
Baker D; Gonzalez-Garcia A; Provisor A.
Maternal toxicity with continuous nevirapine
in pregnancy: results from PACTG 1022.
Journal of acquired immune deficiency
syndromes: JAIDS, 2004, 36.
Farber, Celia. Out of control. AIDS and the
corruption of medical science. Harper’s
Magazine. March, 2006.
Current ethical dilemmas and
controversies
• Shared clinical decision-making
• Genetic screening
• International ethics and IRB review of
international collaboration
• Participant observation and communitybased participatory research
• Non federally-funded research: ethical
framework
Learning Objectives
By the end of this discussion, students will be able to:
1. Recognize how the three ethical principles of academic
research are implemented in clinical settings.
2. List three controversies concerning mass genetic
screening
3. Discuss ethical tensions and conflicts arising from
international collaboration in research.
4. Cite one example in which modalities of communitybased research and participant observation appear to
be in conflict with the IRB doctrine.
5. Discuss the limitations of the IRB doctrine as it applies
to non federally-funded research.
Overview
Despite our comprehensive ethical framework, public health
practitioners are constantly faced with new challenges arising from
the evolving and extended nature of what constitutes “research”.
For example, few or no regulations for the protection of human
subjects are followed by private companies conducting research
with their employees and with their own funds (McDaniel, Solomon
et al. 2006). Another gray area posing unique ethical challenges is
international research (Miller 1988; Kelley 2002; Hyder, Wali et al.
2004). Domestically, the growing tension between the IRB
prescriptive translations of ethical principles and the specific need
of community participatory research is generating ethical issues
that are as yet, unresolved (Malone, Yerger et al. 2006). Next, but
not last or least, examination of genetic variation in large
communities and populations has often been met with heated
controversy over whether such screening and testing, even under
IRB protection, is bound to cast upon entire communities the
stigma of being branded “genetically defective” (Sterling,
Henderson et al. 2006). Using study cases, the final section of
this ethics module will examine these specific examples and
situations of ethical dilemmas and controversies.
Case Study/Discussion Questions
Study Case 1. Genetic Screening
Scientists are turning to genetic variation research in hopes of
addressing persistent racial/ethnic disparities in health.
Despite ongoing controversy, the advancement of genetic
variation research is likely to produce new knowledge and
technologies that will substantially change the ways in which
we understand and value health. They also may affect the
ways in which individuals and groups organize socially,
politically, and economically. Addressing concerns that may
exist in different communities is vital to the scientific and
ethical advancement of genetic variation research. We
review empirical studies of public willingness to participate in
and opinions about genetic research with particular attention
to differences in consent and opinion by racial/ethnic group
membership, (Sterling, Henderson et al. 2006).
Questions
1. What is the impact of genetic screening in
different communities. Cite at least two
examples.
2. What are some of the factors hindering
participation in genetic screening
3. How do consent, values and expectations
vary by race/ethnic membership vis a vis
genetic screening.
Study Case 2.
International research collaboration
BACKGROUND: Increasing collaboration between industrialized and developing
countries in human research studies has led to concerns regarding the potential
exploitation of resource deprived countries. This study, commissioned by the
former National Bioethics Advisory Commission of the United States, surveyed
developing country researchers about their concerns and opinions regarding
ethical review processes and the performance of developing country and US
international review boards (IRBs).
METHODS: Contact lists from four international organizations were used to identify
and survey 670 health researchers in developing countries. A questionnaire
with 169 questions explored issues of IRB review, informed consent, and
recommendations.
RESULTS: The majority of the developing country researchers were middle aged
males who were physicians and were employed by educational institutions,
carrying out research on part time basis. Forty four percent of the respondents
reported that their studies were not reviewed by a developing country IRB or
Ministry of Health and one third of these studies were funded by the US. During
the review process issues such as the need for local language consent forms
and letters for approval, and confidentiality protection of participants were
raised by US IRBs in significantly higher proportions than by host country IRBs.
CONCLUSION: This survey indicates the need for the ethical review of
collaborative research in both US and host countries. It also reflects a desire for
focused capacity development in supporting ethical review of research, (Hyder,
Wali et al. 2004).
Questions
1. What is the National Bioethics Advisory
Commission?
2. List five ethical concerns of researchers in
developing countries
3. What was the gender/age membership of
most researchers surveyed in developing
countries? What are some of the implications
of this gender/age make-up for the
development of an ethical framework in
developing countries?
Study Case 3.
Participant observation and
community-based participatory research
Community-based participatory research (CBPR) addresses the
social justice dimensions of health disparities by engaging
marginalized communities, building capacity for action, and
encouraging more egalitarian relationships between
researchers and communities. CBPR may challenge
institutionalized academic practices and the understandings
that inform institutional review board deliberations and,
indirectly, prioritize particular kinds of research. We present our
attempt to study, as part of a CBPR partnership, cigarette sales
practices in an inner-city community. We use critical and
communitarian perspectives to examine the implications of the
refusal of the university institutional review board (in this case,
the University of California, San Francisco) to approve the
study. CBPR requires expanding ethical discourse beyond the
procedural, principle-based approaches common in biomedical
research settings. The current ethics culture of academia may
sometimes serve to protect institutional power at the expense of
community empowerment.
Questions
1. What is CBPR (Community-based
participatory research)?
2. In the view of the research report’s authors,
how the IRB deliberations hinder CBPR?
3. According to the authors, how the
procedural, principle-based doctrine of the
IRB help sustain institutional power at the
expenses of community empowerment?
Study Case 4.
Non federally-funded research:
ethical framework
In the United States, companies that use their own funds to
test consumer products on their employees are subject to
few regulations. Using previously undisclosed tobacco
industry documents, we reviewed the history of that
industry's efforts to create internal guidelines on the
conditions to be met before employee taste testers could
evaluate cigarettes made from tobacco treated with
experimental pesticides. This history highlights 2 potential
ethical issues raised by unregulated industrial research:
conflict of interest and lack of informed consent. To
ensure compliance with accepted ethical standards, an
independent federal office should be established to
oversee industrial research involving humans exposed to
experimental or increased quantities of ingested, inhaled,
or absorbed chemical agents.
Questions
1. Companies may test consumer products
using their own employees. List three
potential ethical problems with this approach.
2. Specifically, describe how conflict of interest
may arise under this unregulated research
approach
3. Specifically, list three potential ethical
conflicts as a result of conducting research
that lacks an informed consent process
Work Cited and Suggested
Preliminary Module Bibliography (Appended)
Hyder, A. A., S. A. Wali, et al. (2004). "Ethical review of health research: a perspective from
developing country researchers." J Med Ethics 30(1): 68-72.
Kelley, S. D. (2002). "The forum. A contextualized approach to IRB review for collaborative
international research." Ethics Behav 12(4): 371-6.
Malone, R. E., V. B. Yerger, et al. (2006). ""It's Like Tuskegee in Reverse": A Case Study of
Ethical Tensions in Institutional Review Board Review of Community-Based Participatory
Research." Am J Public Health 96(11): 1914-1919.
McDaniel, P. A., G. Solomon, et al. (2006). "The ethics of industry experimentation using
employees: the case of taste-testing pesticide-treated tobacco." Am J Public Health 96(1):
37-46.
Miller, J. (1988). "Towards an international ethic for research with human beings." Irb 10(6): 911.
Sterling, R., G. E. Henderson, et al. (2006). "Public Willingness to Participate in and Public
Opinions About Genetic Variation Research: A Review of the Literature." Am J Public
Health 96(11): 1971-1978.
The Belmont Report [video] : basic ethical principles and their
applications / Produced by the National Library of Medicine for the National
Institutes of Health and the Food and Drug Administration. Imprint [Bethesda, MD] : National
Library of Medicine, [1986?]
Hitti J ; Frenkel LM ; Stek AM ; Nachman SA ; Baker D ; Gonzalez-Garcia A ; Provisor A .
Maternal toxicity with continuous nevirapine in pregnancy: results from PACTG 1022.
Journal of acquired immune deficiency syndromes : JAIDS, 2004, 36.
Farber, Celia. Out of control. AIDS and the corruption of medical science. Harper’s Magazine.
March, 2006.