Responsible Conduct of Research:

Human Subjects, Part 2

Describe the Informed Consent
process for a study in which you have
been involved?
 Objectives
• Define informed consent
• Review privacy and confidentiality in research
• Evaluate methods of subject recruitment
• Discuss international human subjects research
 What is it Informed consent?

“Informed consent is a decision to participate in research, taken by a

competent individual who has received the necessary information;
who has adequately understood the information; and who, after
considering the information, has arrived at a decision without having
been subjected to coercion, undue influence or inducement, or
intimidation.” CIOMS 2002

http://www.cioms.ch/frame_guidelines_nov_2002.htm Accessed on
March 15, 2013
 Still on consent

Informed consent is the knowledgeable authorization by a

patient (in the case of clinical practice or study) to authorize
medical intervention, and one that is in accord with the
patient's values and preferences; or in biomedical research, a
process by which a prospective participant indicates his or
her willingness to be part of a research or study
 Purpose of informed consent

Emanuel et al. (2000: 2706) identify a 2-fold purpose of I/C as

follows:

“to ensure that individuals control whether or not they

enroll in clinical research and participate only when the
research is consistent with their values, interests, and
preferences.”
 Still on purpose

• To protect patients/research participants from exploitation by

investigators

• To protect researchers/sponsors/institutions from unnecessary

litigations arising from research

• To ensure that research is conducted according to accepted

ethical norms or principles

• Serves as a statement of contract between researchers and

participants
 Grounds for informed consent

Robert Levine argues thus:

“the firmest grounding for the requirement to seek consent is

the ethical principle ‘respect for persons’- a principle which,
when interpreted in a Kantian sense stipulates that research
subjects will be treated as an end and not merely as a means
to another’s end”
 Informed Consent
• Major component of Declaration of Helsinki,
Belmont Report, U.S. Food and Drug
Administration and U.S. Department of Health
and Human Services Regulations, and Good
Clinical Practice guidelines
• Process, not a form
• Key element of research involving human
subjects
 Informed Consent
• Trial involves research, purpose of trial, trial
treatment, probability of assignment to each
group
• Procedures to be followed, subject’s
responsibilities, aspects of trial that are
experimental
• Foreseeable risks/inconveniences, benefits,
alternatives
• Compensation/treatment in event of injury
 Informed Consent
• Anticipated payment for participation
• Anticipated expenses
• Participation is voluntary, may refuse to
participate or withdraw without penalty or loss
of benefits
• Monitor, auditor, IRB, and regulatory
authorities have access to medical records for
verification, without violating confidentiality
• Records identifying the subject will be kept
confidential
 Informed Consent

• Subject will be informed in a timely fashion

about new information relevant to
continued participation
• Person to contact for further information
and for trial-related injury
• When participation may be terminated
• Expected duration of the trial
• Approximate number of subjects to be
studied
 Informed Consent

• Subject should receive copy of informed

consent before starting study, and updates
as appropriate
 5 minute conversation

• How can a non-scientist, non-clinician evaluate what

‘risk’ means in a clinical study?
– Would they know the difference between a 2% risk
and a 5% risk?
– Would they know the difference between a “very
small risk” and a “slight risk” or a “small risk”?
• How much should they be told about details that they
can’t really understand but might scare them off?
 Objectives
• Define informed consent
• Review privacy and confidentiality in research
• Evaluate methods of subject recruitment
• Discuss international human subjects research
 Privacy and Confidentiality

• Procedures must be developed to protect the privacy

of subjects and the confidentiality of their
medical/research data.
• Research subjects must be informed about the extent
to which records will be kept confidential, including a
description of who may have access to the research
records.
 Privacy and Confidentiality

• HIPAA (Health Insurance Portability and

Accountability Act)
– US law to protect privacy of health information
• Genetic information
– NIH requirement to contribute DNA and other
research participant information to central
repository for Genome-wide Association
Studies (GWAS)
 Stored Samples
Tissue, blood or DNA

• Was consent obtained for future research?

• If not:
– Were samples collected in distant past?
– Are they anonymous/de-identified?
– Is someone who has identifying information removing
the identifiers and providing de-identified data?
• Was consent obtained only for specific uses?
• Was consent time-limited (e.g., 10 years)?
 Stored Samples

• If consent was not obtained for future research,

samples can only be used if:
– Research involves no more than minimal risk;
– Waiver/alteration of consent will not adversely
affect the rights and welfare of the subjects;
– Research could not be practicably carried out
without the waiver or alteration; and
– Whenever appropriate, subjects will be provided
with additional information after participation
 Objectives
• Define informed consent
• Review privacy and confidentiality in research
• Evaluate methods of subject recruitment
• Discuss international human subjects research
 Subject Recruitment

• Media advertising (e.g., print, radio, TV)

• Posters
• Physician-to-physician letters
• Direct to patient letters/phone calls
Issues in Recruiting Human Subjects

• Recruitment incentives (“bonuses”)

• Dual Investigator-physician role
– What is best for the subject vs. what is best for
the protocol
• Confidentiality of medical records
• Financial disclosure – to subjects, regulators
• Subject compensation
 Objectives
• Define informed consent
• Review privacy and confidentiality in research
• Evaluate methods of subject recruitment
• Discuss international human subjects research
 Why International Research?
• Economic, epidemic, and regulatory
contributions to the “fluid map” of clinical
trials (Petryna 2006)
– Economic: recruitment costs, background costs
– Epidemic: numbers of patients, lack of access to
care
– Regulatory: 1994 change in NIH rules, many
countries have loose research oversight
 Whose Standards Apply?
• Lurie & Wolfe 1997
• How do we resolve issues of context when
considering the ethics of research?
– Context and the experiment-therapy dilemma
– Context and clinical equipoise
• What should be considered the standard of
care?
 Providing Care through Clinical Research:
Incentive, Exploitation, or Benefit?
Some of our patients cannot pay for antiretrovirals, "not even
one baht" (THAIDS pediatrician)

• When can the export of clinical research reflect principles of

justice – both risks and benefits?
• When can a person be considered vulnerable to a potentially
exploitative clinical trial?
 Post-study Care
“Although we stated clearly in our consent forms that we could not
promise post-trial drug supply, we were compelled to take action when
faced with the tragic prospect of watching patients reversing their
excellent quality of life gained while on antiretrovirals”
“During the first few years at THAIDS…we not strong enough” to require
post trial drug support for former study subjects, because companies “just
go to some other site”

•How do we account for post-study care within current ethical

structures?
•How can we balance public health impact of clinical trials
with individual impact for participants?
 What is Owed Local Medical Systems?
For example, right now, we are going to do a nutritional trial using some biscuits
from [Europe]. To be given to people who still don’t need the antiretrovirals, to
see the immune response, something like that, as compared to placebo. Just look
at the CD4+ count, viral load, and the clinical manifestations. We proposed that
we should do a good nutritional assessments. Anthropometrics…biochemical
assessment, and nutrition (macronutrients, micronutrients, and so on). Although
this was not initially put in as one, in the protocol. So we try to submit as a sub-
study. We don’t know how, how lucky we will be able to convince the sponsor to
do that. But this is something we think,…because as I always think, if we are
going to do research for this types of study, for biscuits, instead of being
beneficial for the biscuit producer we should have some benefit for our own, in
terms of our own interest in nutrition, in some…so we can do some of our own
research.
(HIV research clinic director, Thailand)
 Context and Informed Consent
Norms in Northern Nigeria Informed consent questions
• Age of majority for women: • When does a participant
16 or at marriage need parental consent?
• Married women have no • Can a woman give
recognized autonomy from independent consent?
their husbands • What if a woman wishes to
• Consequences of divorce participate, but the
include loss of property, husband disagrees?
severing of rights to • What if a woman does not
children, and no mechanism wish to participate, but the
for alimony husband disagrees?
 Logistics of Clinical Trials
• What are the consequences of the form of
clinical trials, and how do these forms interact
with patient vulnerability?
– Parachute research
– Annexed sites
• IRBs, Ethical Boards, local oversight: Do they
work?
– Documentary compliance vs. deep compliance
Philosophical basis of I/C

 Based on several lines of philosophical reasoning: the need

to protect and maintain human dignity

 Based on the Hippocratic admonition “to help, or at least, to

do no harm”- a way to promote patient or subjects’ benefit
and welfare
 Philosophical basis of I/C

 I/C can be justified on the grounds of social benefit:

producing the “greatest good for the greatest number”
(utilitarianism)

 Based on the ethical norm of “respect for persons”- not to

treat persons as means but as ends (Kantianism)
 Religious basis for I/C

Some basic tenets of religions provide a basis for

informed consent, e.g., the teaching that each
individual’s life is a gift from God and is of infinite
worth (the “sanctity of life”)
 Legal basis

The Nuremberg trials and sentencing of Nazi physicians after

WW II and some other cases of litigation arising almost
exclusively in the context of medical practice provide legal
grounding for informed consent, e.g., a 1914 legal judgment in
America: Schloendorff v. Society of New York Hospital

This is a case about court findings that surgery ought not to

have been performed on a patient who had agreed to an
abdominal examination under anaesthesia but had declined an
operation
 The legal basis (2)

The Schloendorff v. Society of New York Hospital case is one

about court findings that surgery ought not to have been
performed on a patient who had agreed to an abdominal
examination under anaesthesia but had declined an
operation
 The legal basis (3)

In the famous statement which eloquently

expressed the view of the right of competent
people to self-determination, the Judge
demurred, saying:

Every human being of adult years and sound mind has a right to
determine what shall be done with his own body; and a surgeon
who performs an operation without his patient’s consent
commits an assault.
• What are some Informed Consent
issues you think need to be
addressed to responsibly conduct
research?
University Policies and Procedures
Questions & Discussion