Ethics of research involving vulnerable subjects.pptx

DILLA UNIVERSITY
COLLEGE OF HEALTH SCIENCE AND MEDICINE
Seminar on Ethics of research involving vulnerable subjects
Prepared by: - Melkam Andargie

Ethics of research involving vulnerable subjects
• The federal research regulations do not explicitly define
“vulnerable subject”.
• But they include an explicit definition: “When some or all of
the subjects are likely to be vulnerable to coercion or undue
influence,
• Additional safeguards have been included in the study to
protect the rights and welfare of these subjects.
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Ethics of research involving vulnerable subjects Cont…
• The Helsinki Declaration also provides guidance on research
involving vulnerable subjects: specifically considered protection.
• Medical research with a vulnerable group is only justified if the
research is responsive to the health needs or priorities of this group
and the research cannot be carried out in a non-vulnerable group.
• In addition, this group should stand to benefit from the knowledge,
practices or interventions that result from the research.
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• Likewise, The Council for International Organizations of
Medical Sciences (CIOMS) guidelines requires additional
protections for vulnerable subjects:
– When vulnerable individuals or groups are considered for
recruitment in research, researchers and research ethics
committees must ensure that specific protections are in
place to safeguard the rights and welfare of them.
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• CIOMS guideline in 2002 and 2016 versions also includes sections which address
research involving children, pregnant women, and adults with mental disabilities or
diseases that affect decision-making.
 Research regulations an ethical guidance include the following types of additional
protections for vulnerable subjects:
 Justification for including vulnerable subjects in research,
 Limits on research risks,
 Safeguards for Consent,
 Safeguards for privacy/confidentiality and
 Benefit sharing.
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• Foetuses/pregnant women, Neonates, and Infants and young children are
vulnerable subjects to both Risk and exploitation.
• Older children and adolescents, mentally disabled or ill adults, Military
personnel, Employees and seriously ill patients are vulnerable subjects to
Risk, decision-making, exploitation. Impoverished people and racial/ethnic
minorities are also vulnerable subjects to exploitation.
• Individuals lacking language proficiency and Elderly are vulnerable
subjects for decision-making.
• Disaster victims and Students also are vulnerable to decision-making and
risk
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Research Involving Children
• Children are the first type of vulnerable subject.
• Under the Common Rule, an IRB may approve three types of paediatric
research:
a) research that does not offer direct benefits to the subjects but is minimal
risk;
b) research that offers directs benefits to the subjects; and
c) research that does not offer direct benefits to the subjects but is minor
increase over minimal risk and is likely to yield generalizable knowledge
about the subject’s disorder or condition.
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Research Involving Children cont…
• McCormick (1974) published an essay in Perspectives in Biology and
Medicine in which he argued that children can participate in research with
their parents’ proxy consent.
• Ramsey (1976) strongly objected to McCormick’s view because it treats
children as moral agents who are obligated to contribute to society.
• Ramsey argued that we should not ascribe duties of beneficence to children
because they are developing persons and not fully moral agents. After
much deliberation, the National Commission sided with McCormick.
• The federal research regulations reflect McCormick’s view that it is
acceptable to enrol children in some types of non-beneficial, low-risk
research.
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Research Involving Adults with Mental Disabilities or
Diseases that Impair Decision-Making
• Adults with mental disabilities or diseases that impair decision-
making need additional protections in research because they may
have compromised ability to consent to research participation.
• A dementia patient may not have adequate memory or reasoning
skills to make competent decisions.
• Likewise, an adult with psychosis may also have impaired cognitive
abilities, especially if his or her condition is not well-controlled.
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• The federal research regulations do not include any special rules for
protecting mentally disabled or ill adults in research or place any
limitations on the risks that these subjects may be exposed to in research.
• One reason why the federal regulations may not include additional
protections for mentally disabled or ill adults is that these subjects are a
highly diverse group: some mentally ill or disabled adults may have good
decision-making abilities, while others may not.
• Also, some may be able to make decisions under certain conditions (e.g.
when their condition is controlled by medication) but not others.
Diseases that Impair Decision-Making cont…
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• Most commentators agree that adults with mental disabilities or
diseases that may impair decision-making should not be included in
research unless there is a sound scientific justification.
• There are often good scientific reasons for including mentally
disabled or diseased adults in research. For example, researchers
may want to learn more about psychosis, depression, dementia, drug
addiction, traumatic brain injury, and other diseases or conditions
that can impair decision-making.
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• Some adults may develop mental illnesses or disability while
they are participating in long-term studies.
• Research protocols that include adults with mental disabilities
or diseases that may impair decision-making should include
procedures for assessing the subject’s decision-making
capacity and
• identifying a legally authorized representative (LAR) if the
subject is incapable of providing consent.
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• In some cases, adults with declining mental abilities may sign advance
directives for research participation when they are still competent.
• Research advance directives are similar to other advance directives, such as
living wills, in that they allow competent adults to express their preferences
concerning certain decisions before they lose their mental faculties.
• Research advance directives promote the competent adult’s autonomous
decision-making by allowing him or her to decide whether to participate in
research.
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• One issue that may arise in assessing decision-making capacity
is that investigators or members of the research team may have
a conflict of interest that could bias their judgment.
• To minimize the potential for bias, investigators could use a
formal decision-making capacity assessment tool or have an
independent party assess decision-making capacity.
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• Most commentators agree that enrolling adults with mental disabilities or
diseases that may impair decision-making capacity in minimal risk research
does not raise any special ethical concerns because it does not expose them
to significant risks.
• Enrolling these subjects in medically beneficial research does not raise
special ethical concerns because it offers them benefits (such as treatment)
which compensate them for risk exposure.
• The ethical issues with enrolling these adults in more than minimal risk,
non-beneficial research are similar to those that arise with enrolling
children in these types of studies, since the research subjects have not
consented to participation.
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Research Involving Pregnant Women
• Investigators and research sponsors routinely excluded all
women, not just pregnant women, from clinical trials.
• The reasons for excluding women from clinical trials were
twofold.
• First, many were concerned about the legal liability arising
from harms to the foetus from in utero exposures to drugs,
radiation, or other interventions or procedures.
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• The reasons for excluding women from clinical trials were
twofold.
• First, many were concerned about the legal liability arising
from harms to the foetus from in utero exposures to drugs,
radiation, or other interventions or procedures. The
thalidomide tragedy of the 1950s and 1960s was still fresh on
investigators’ and sponsor’s minds.
Research Involving Pregnant Women cont…
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• Thousands of children whose mothers had taken this drug to
control nausea during pregnancy were born with severe birth
defects, such as stunted limbs.
• The tragedy affected mostly European children, because the
Food and Drug Administration (FDA) was still reviewing
thalidomide when the adverse effects of the drug surfaced.
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• Investigators and sponsors believed that, to be on the safe side, all women
should be excluded from clinical trials, because;
• Female research subjects might have false negative Px tests, and even if a
woman were not pregnant during the study, the effects of the drug might
linger and cause foetal harm if she subsequently became pregnant.
• Many believed that the female reproductive cycle was an uncontrolled
variable that could make it difficult to interpret clinical trial data.
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• Investigators and sponsors were concerned that female
hormones, such as oestrogen and progesterone, might interact
with medications and confound clinical trial data.
• During the 1980s, women’s health advocates argued that
investigators and sponsors were unfairly excluding women
from clinical research and that these policies had a negative
impact on women’s health.
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• Since women and men are physiologically different, results from studies of
the safety and efficacy of a treatment in men might not readily apply to
women’s health care.
• Physicians might not know whether a drug affects women differently than
men, or how to dose the drug in women, for example.
• Women’s health advocates also argued that diseases that affect mostly
women, such as breast cancer, were understudied.
• In response to these concerns, Congress passed laws requiring the National
Institutes of Health (NIH) and FDA to develop policies for including
women and minorities in research.
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• The NIH requires that funded-investigators include women
and minorities in research unless there is a legitimate scientific
or ethical reason for exclusion.
• For example, women do not need to be included in a study of
prostate cancer, because they do not have prostates.
• Pregnant women may be excluded from more than minimal
risk studies that do not offer benefits to the women or foetus to
comply with federal regulations
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• Foetuses are extremely susceptible to harm from exposures to drugs in
utero.
• Drugs can harm the foetus by:
1) Crossing the placenta and acting directly on the foetus;
2) Impairing the function of the placenta and restricting blood flow to the
foetus;
3) Causing the uterus to contract prematurely; and
4) Lowering the woman’s blood pressure which can reduce blood flow to the
foetus.
• Two to three percent of birth defects result from medications taken during
pregnancy.
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• Investigators and sponsors are justifiably hesitant to include pregnant
women in clinical trials, given the potential for foetal harm.
• As a result of the reluctance to include pregnant women in clinical drug
trials, less than 10% of the medications approved by the FDA contain
information in the labelling pertaining to the risk of birth defects.
• Given the lack of knowledge about how drugs affect the developing fetus,
many clinicians advise women to refrain from taking any unnecessary
medications during pregnancy and to taper off medications prior to
attempting to conceive.
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• Despite these concerns, investigators and sponsors might decide that
it would be important to include pregnant women in a drug study to
promote women’s health.
• Some women must take medications during pregnancy to manage
illnesses, such as hypertension, diabetes, asthma, epilepsy, or
depression, which could threaten their life or health if untreated.
• Lack of knowledge about how these medications affect pregnant
women or their fetuses could lead to unsafe prescribing practices.
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• Before initiating a drug study that will include pregnant
women, investigators should evaluate the evidence about
potential teratogenicity effects of the drug from FDA
databases, human observational studies, and animal
experiments.
• If investigators decide to exclude pregnant women from a
study, they should require fertile females to take a pregnancy
test prior to enrolment.
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• As a side note, while much of the ethical and regulatory discussion
concerning research-related birth defects has focused on the pregnant
woman, it is important to realize that a father’s toxic exposures may also
impact the fetus.
• Some studies have shown that paternal genetic or epigenetic damage
caused by drugs, toxic chemicals, pesticides, or radiation can be transmitted
to offspring.
• Investigators should keep this in mind when designing clinical trials and
informing men about potential risks to their children from exposures to
radiation or drugs
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Reference
• Chen, D.T., F.G. Miller, and D.L. Rosenstein. 2002. Enrolling decisionally impaired
adults in clinical research. Medical Care 40 (9 Suppl): V20–V29.
• Jonsen, A.R. 2006. Nontherapeutic research with children: The Ramsey versus
McCormick debate. Journal of Pediatrics 149 (1 Suppl): S12–S14.
• National Bioethics Advisory Commission. 1998. Research involving persons with mental
disorders that may affect decisionmaking capacity. Washington, DC: National Bioethics
Advisory Commission.
• Rosenstein, D.L., and F.G. Miller. 2008. Research involving those at impaired risk for
decisionmaking capacity. In The Oxford handbook of clinical research ethics, ed.
E.J. Emanuel, C. Grady, R.A. Crouch, R.K. Lie, F.G. Miller, and D. Wendler, 437–445.
New York: Oxford University Press.
• World Medical Association. Ethical principles for medical research involving human
subjects (2013 revision).
• Centers for Disease Control and Prevention 2016. Medications and pregnancy.
14/10/2022 28

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