Family Studies Issues
Convener: Georgia Weisner
Collaborators: Melissa Barber, June Cassano, Eric Juengst, Eric
Kodish, , Patricia Marshall, Anne Matthews, Max Mehlman, Mary
Quinn Griffin, Eric Topel, Peter Whitehouse, Chris Winkelman
Under the leadership of Dr. Wiesner, this CGREL research group
focuses on developing and conducting studies to increase
our understanding of the research ethics surrounding genetic
family studies. The issues of privacy, informed consent, and
psychosocial dynamics within the family are examined as
they relate to specific phases of family studies. Relevant topics
include: enrollment and participation; inclusion of non-participating
family members in pedigree analysis; data collection; genetic
sample collection and storage; generation of genetic markers;
genetic analysis. Further, this group works with other CGREL
groups in addressing the ethics of research conduct when translating
gene discoveries to the clinic, tissue-based gene identification
research, and gene transfer research.
Specific Aims:
1. To annotate and compare the research protocols of four CWRU
family-based genetic studies that differ in health-related risks.
Each step of the research protocol, including contact, enrollment,
collection of clinical information, collection of family information,
collection of genetic samples, generation of genotypes, statistical
analysis, and (potential) disclosure of results, will be analyzed
in each study.
2. To assess the level of concern expressed by the participants
and family members in each of these four studies with regard
to contact, enrollment, informed consent, time required of the
participant, and use of pedigree information in research studies.
Rationale:
Our current understanding of human genetic disease is a direct
result of family studies research over the last half-century.
The benefits of this research have been enormous, and range
from the discovery of specific genes that cause common diseases,
such as cancer or heart disease, to a deeper understanding of
the mechanics of how environmental factors interact with the
human genome or set of genes. However, these advances in genetic
science often alarm the lay public. In 1990, one harsh view
was that scientists " have given no more thought to the
potential social applications of genome mapping and sequencing
than Victor Frankenstein had given to the consequences of creating
his monster …". 46
Nevertheless, genetic studies based on research with extended
families (collectively known as pedigree or family studies)
are now the mainstays of biomedical research. Family pedigree
studies were previously considered to have little, if any, inherent
ethical conflicts by researchers in the field because the studies
were often based on observations of a rare condition in a small
number of families. In joining a proposed research study, these
families were eager to discover the genetic link to their condition,
and often worked closely with the research team. The potential
impact of this research was limited to a few families with these
unusual disorders. In contrast, present-day family pedigree
studies are often focused on the familial nature of common diseases
and are conducted on a national and international scale. Contemporary
family pedigree projects are a hybrid between standard epidemiological
research and molecular analysis of gene function, in which large
numbers of individuals and their family members are enrolled
to identify genes that cause human disease. Thus, these studies
can potentially impact many more people in communities across
the country.47
A crucial difference between family pedigree studies and other
biomedical research lies in the collection and analysis of information
on family groups, rather than unrelated individual volunteers.48
Because epidemiologic protocols analyze clinical information
on a large number of cases, the risks and benefits of these
studies stem from the potential impact on an individual volunteer.
In contrast, the information gained from one family member in
family pedigree research can lead to consequences for other
family members.49 Holtzman and Andrews further argue that genetic
research "is different because it often involves testing,
and thus creates genetic information about individuals and groups
that did not exist before."50 As a result, participation
in genetic research can have significant psychosocial consequences
for research volunteers.51 By enrolling in a pedigree research
study, participants must face concerns over the propensity to
develop a disease, potential genetic discrimination, and the
consequences of medical decisions based on perceived risk for
disease. Human geneticists who study rare monogenic disorders
have recognized these psychosocial issues for many years.52
Current and future researchers aided by the enormous growth
in genetic research will focus on common disease processes.
In this way, a greater proportion of the general population
could potentially learn about being at risk for health problems
because a relative participated in a family pedigree study.
Thus, as genetic family-based studies become more prevalent,
the potential for unforeseen harm to participants and their
family members will increase.53
Controversies arising from these harms can have significant
impacts on the genetic research enterprise by undermining public
trust. Recent debates over the status of extended family members
as "involuntary human subjects" in genetic family
studies provide one example of this phenomenon.54 This controversy
has led to the Office for Human Research Protections requiring
informed consent from all "secondary subjects" in
family studies, which researchers worry will lead to an overly
restrictive research environment. For some, it is not clear
that these additional family members meet the definition of
a 'human subject" for informed consent purposes, or how
best to recruit them if they do. Others believe that family
history information "belongs" to the person reporting
the family history, and not to each individual in the pedigree.55
Botkin published guidelines for pedigree research in 2001 to
assist researchers and local IRBs to: 1) determine if the additional
family member is a research subject; 2) determine whether informed
consent can be waived. He recommends that the "general
sensitivity of the information" gathered from probands
about family members be taken into account when the IRB determines
the need for prior consent from family members. He suggests
that common diagnoses (e.g., cancer, diabetes, heart disease)
have lower levels of sensitivity and risk, while other conditions
(e.g., criminality, alcoholism or psychiatric disorders) are
considered more sensitive; if the issues being studied are sensitive,
the relatives might be exposed to a higher level of risk by
the research protocol.56
One difficulty in resolving these potential conflicts is that
there is little known about the research participant's thoughts,
concerns, and fears about enrolling and partaking in genetic
family studies. Few studies testing specific hypotheses about
research ethics have been reported regarding the participants'
views about the level of privacy and confidentiality of family-based
information.57 Juengst has suggested that what the social sciences
tell us about three virtues that Americans endorse for family
life-i.e., loyalty, security, and intimacy, can be used to suggest
hypotheses about the kinds of moral tensions that one might
expect new genetic information to produce within different kinds
of American families.12 This is a conceptual framework that
now needs to be returned to the social sciences for testing
and cross-cultural revision in the context of actual family
studies. Further, a review of the literature did not find any
reports exploring the impact more stringent requirements might
have on the researcher. The research of this group is designed
to meet these needs.
|
