Transcript Guidelines for the ethical conduct of research

Guidelines for the ethical
conduct of research
Marcalee Sipski, MD
Professor and Director of Neuroscience Research
University of Alabama Dept. of PM&R
Adapted from
NIH Offices of Human Subjects Research Guidelines for the Conduct of
Human Subjects Research at the NIH
History
The Nuremberg Code



In 1946 23 Nazi physicians went on trial for
crimes committed against POW.
Crimes included exposure of humans to
extremes of temperature, performance of
mutilating surgery and deliberate infection
with a variety of lethal pathogens
Fundamental ethical standards for the
conduct of research were codified
The Nuremberg Code




Reflected in the Declaration of Human Rights and
accepted in principle by each of the 51 original
signatory nations of the Charter of the United
Nations.
10 conditions that must be met in order to justify
research involving human subjects
Voluntary informed consent of subjects
Scientifically-valid research design that would
produce fruitful results for the good of society
1953-NIH Clinical Center
 The 1st US Policy for
protection of human subjects
 Gave special protection to
adult health research
volunteers who had little to
gain from research
participation
 Prospective review of
research from persons
without direct involvement or
investment in the work-the
start of the IRB
1960’s
 With the greater
increase in human
rights, interest grew in
the rights of research
subjects
 Newspaper reports of
investigators in NY
injecting elderly indigent
people with live cancer
cells (without their
consent) to learn more
about the immune
system
1966
 A highly respected
anesthesiologist and
physician-investigator
shocked the medical
community when he
reported that unethical
or questionally ethical
practices were common
in human subjects
research in many of
America’s premier
research institutions
The Helsinki Recommendations




Biomedical research should conform to
accepted scientific principles
IRB’s must be used
Research must be conducted under the
supervision of an appropriately trained
medical person
The question must be as important as the
risk
The Helsinki Recommendations








Concern for the interests of the subject must always prevail over the interests of
science and society.
The subject’s privacy must be protected along with their physical and emotional
integrity
Research hazards must be predictable
When publishing results, they must be accurate
Each potential subject must be adequately informed of the aims, methods,
anticipated benefits and potential hazards of the study and the discomfort it may
entail. They must also know they can quit at any time.
The physician should then obtain the subject’s freely-given informed consent,
preferably in writing.
The issues of dependent relationships, legal incompetence and minors should be
consider when performing research
Research protocols should include a statement of the ethical considerations involved
Clinical Research






In the treatment of the sick person, the physician must be free to use a new
diagnostic and therapeutic measure, if in his or her judgement it offers hope of
saving life, reestablishing health or alleviating suffering.
Potential benefits, hazards and discomfort of a new method should be weighed
against the advantages of the best current diagnostic and therapeutic methods.
Every patient -- including those of a control group, if any -- should be assured
of the best proven diagnostic and therapeutic method.
Refusal of the patient to participate in a study must never interfere with the
physician-patient relationship.
If the physician considers it essential not to obtain informed consent, the
specific reasons for this proposal should be stated in the experimental protocol
for transmission to the independent committee
The physician can combine medical research with professional care, the
objective being the acquisition of new medical knowledge, only to the extent
that medical research is justified by its potential diagnostic or therapeutic value
for the patient.
Non-clinical biomedical research




It is the duty of the physician to remain the protector of
the life and health of that person on whom biomedical
research is being carried out.
Subjects should be volunteers
Investigator or the investigating team should discontinue
the research if in his/her or their judgement it may, if
continued, be harmful to the individual.
The interest of science and society should never take
precedence over considerations related to the wellbeing
of the subject.
1966: HEW Policy


Applied to all human subjects research conducted
or support by HEW
Prospective review of HSR, taking into account
the rights and welfare of the involved subjects, the
appropriateness of informed consent procedures,
and the risks and potential benefits of the
procedures. Consent was required to be
documented and signed by subjects or their
representatives
Tuskegee Syphilis Study
Tuskegee





The reason why Macon County was chosen was explained by The Health Service's Taliford Clark
in a report, "Macon County, is a natural laboratory; a ready-made situation. The rather low
intelligence of the Negro population, depressed economic conditions, and the common
promiscuous sex relations not only contribute to the spread of syphilis but the prevailing
indifference with regard to treatment."
Free medicine for the treatment of "Bad Blood" brought 600 subjects into the study, 399 were
suffering from syphilis and the remaining 201 were a control group. None of the participants were
ever told that they had the disease, nor were they ever told that an experiment was taking place.
Subjects of the experiment had treatment for syphilis deliberately withheld from them. During
World War II, they were kept out of the draft by the PHS, because joining the army would have
meant a blood test and treatment for the disease if it had been discovered. The subjects were
kept out of national programs that would have led to a cure.
Experiment continued until 1972 whistle blower
Results contributed nothing: syphilis led directly to the deaths of 28 of the participants, a further
100 died of related complications, 40 spouses were infected and 19 children were born with
congenital syphilis
Senate committee on labor and human
resources




Held hearings on the Tuskegee study and other
alleged health care abuses of prisoners and
children which led to . . . . . .
1)enactment of the National Research act of 1974
2)National Commission for Protection of Human
Subjects of Biomedical and Behavioral Research
3)Imposition of a moratorium on research
conducted or supported by HEW involving live
human fetuses until the National Commission
could study and make recommendations on it
National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research




Functioned from 1974-78
Evaluated the existing HEW system and
recommended improvements
Issued reports on research involving
pregnant women, live human fetuses,
prisoners, children, the mentally disabled
and the use of psychosurgery
Also, issued The Belmont Report
The Belmont Report: 3 principles

Respect for persons: acknowledges the
dignity and autonomy of individuals.
Requires informed consent for research
and requires that people with diminished
autonomy such as live human fetuses,
children, prisoners, the mentally disabled,
and people with severe illnesses be
provided with additional protections
The Belmont Report: 3 principles

Beneficence requires us to protect
individuals by maximizing anticipated
benefits and minimizing harms. This
requires carefully examination of study
design along with risks and benefits
including at times identifying alternative
ways of obtaining benefits sought from
research. Research risks must always be
justified by expected research benefits.
The Belmont Report: 3 principles


Justice requires that we treat subjects fairly. Subjects
should be carefully and equitably chosen to insure that
certain individuals or classes of individuals such as
prisoners,elderly people or financially impoverished people
are not systematically selected or excluded unless there
are scientifically or ethically valid reasons for doing so.
Unless there is justification for an exception, research
should not involve persons from groups that are unlikely to
benefit from subsequent applications of the research.
So what does this mean for your
university?


Title 45 Code of Federal
Regulations, Part 46 Protection of
Human Subjects (45 CFR Part
46)—Framework in which
investigators can ensure efforts
have been made to protect the
rights and welfare of research
subjects
Each research institution studying
human must have their policies
for subject protection in an
“assurance of compliance”
So what does this all mean for you?


Institutional Review
Board
Principal investigators
are responsible for
protecting the rights
and welfare of the
human subjects who
participate in their
research
Does your research involve human
subjects?


A “human subject” is a
living individual about
whom an investigator
obtains either 1)data
through interaction or
intervention with the
person or 2)identifiable
private information
Many times the lines are
blurred
Activities that are generally exempt. . .
The collection and study of. . . . .





Samples from deceased individuals
Samples collected only for diagnostic purposes
Samples or data available from commercial or
public repositories or registries
Established cell lines that are publicly available to
qualified scientific investigators
Self-sustaining, cell-free derivative preparations
including viral isolates, cloned DNA, or RNA
Six categories of Research that are
generally exempt


Research conducted in established or commonly accepted
educational setting, involving normal educational practices e.g.(i)
research on regular and special education instructional strategies,
or (ii) research on the effectiveness or comparison of instructional
techniques, curricula, or classroom management methods
Research involving the use of educational tests, survey procedures,
interview procedures or observation of public behavior, unless: (i)
Information obtained is recorded in such a manner that human
subjects can be identified, directly or through identifiers linked to the
subjects; and (ii) any disclosure of the human subjects' responses
outside the research could reasonably place the subjects at risk of
criminal or civil liability or be damaging to the subject's financial
standing, employability, or reputation.
Six categories of Research that are
generally exempt


Research involving the use of educational tests (cognitive,
diagnostic, aptitude, achievement), survey procedures, interview
procedures, or observation of public behavior that is not exempt
under paragraph (2) above if: (i) The human subjects are elected or
appointed public officials or candidates for public office; or (ii)
federal statutes(s) require(s) without exception that the
confidentiality of the personally identifiable information will be
maintained throughout the research and thereafter.
Research, involving the collection or study of existing data,
documents, records, pathological specimens, or diagnostic
specimens, if these sources are publicly available or if the
information is recorded by the investigator in such a manner that
subjects cannot be identified, directly or through identifiers linked to
the subjects.
Six categories of Research that are
generally exempt


Research and demonstration projects which are conducted by or
subject to the approval of department or agency heads, and which
are designed to study, evaluate, or otherwise examine: (i) Public
benefit or service programs; (ii) procedures for obtaining benefits or
services under those programs; (iii) possible changes in or
alternatives to those programs or procedures; or (iv) possible
changes in methods or levels of payment for benefits or services
under those programs.
Taste and food quality evaluation and consumer acceptance
studies, (i) if wholesome foods without additives are consumed or
(ii) if a food is consumed that contains a food ingredient at or below
the level and for a use found to be safe, or agricultural chemical or
environmental contaminant at or below the level found to be safe,
by the Food and Drug Administration or approved by the
Environmental Protection Agency of the Food Safety and Inspection
Service of the U.S. Department of Agriculture.
Elements of a Research Proposal



Must receive approval from the IRB before beginning your
study
Proposal is a written description of, and scientific rationale
for, the proposed research activity. It includes a discussion of
the human subject protection issues that are relevant to the
study and addresses, at a minimum: the risks to subjects; all
procedures which are experimental; the anticipated benefits
to subjects, if any; the anticipated number of subjects; the
proposed consent document and consent process to be
used, and appropriate additional safeguards if potentially
vulnerable subjects are to be enrolled. e.g.
the elderly, prisoners, children, cognitively impaired
individuals, or people who are economically or educationally
disadvantaged.
What is the IRB evaluating?


Is study design
consistent with sound
scientific principles
and ethical norms?
Does the protocol
meet project
assurance criteria for
approval?
What is the IRB evaluating?


Have the necessary
elements of informed
consent been fulfilled?
Are additional
appropriate
safeguards provided if
potentially vulnerable
subjects are to be
studied?
As one can see the IRB process can be
quite painful and expensive. . . .
So, who is on the IRB anyway?




Representatives from
various professional
disciplines
Someone from the
clergy
A consumer
representative
Potentially someone to
protect vulnerable
parties
Elements of Informed consent: In Lay
Language









Description of the study
Description of inclusion and exclusion criteria
Number of subjects
Anticipated risks
Anticipated benefits
Information about the study sponsor
Rights as a research subject
Who to contact
Financial information
Practical Issues with regards to Human
Subjects Protection





You must indicate to the IRB how you will recruit
and advertise for study subjects
Copies of Advertisements must be provided
It is fair game to approach your own patients
verbally
It is often useful to come up with a consent to
provide patients to be included on future mailing
lists for involvement in clinical trials
When you do send out mailings it is the norm to
provide a number where people call for
information about the study
Practical Experiences from A Sex
Researcher




Realize that many personalities exist on
IRB’s
Realize that when you are younger, many
senior people feel as if it is their perogative
to direct you
Realize that the rules constantly change
Make sure you cross your ts and dot your is
HIPPA


Generally with most IRB applications you
must also complete a HIPPA checklist and
appropriate documentation
Potential data identifiers are lengthy
Practice makes perfect

An exercise to understand what you need
to put in a consent form. . . .