Research Ethics, Human Subjects
and Data Management
Or,
Why Bad Cases Make Tough Laws!
Objectives: By the end of this lecture....
•
1. You will have stopped wondering why there are so many
conflicting results out there.
2. You will have stopped wondering why there are so many
hoops to jump through in order to do research.
3. You will realize that the honest person has many
blessings, not the least of which is that they don't have to
keep track of what they lied about.
4. You will be able to assess whether someone else's
research has been conducted in an ethical manner, and
know how to go about planning and conducting ethical
research yourself, with the appropriate guidance.
History Lesson:
• The Three Wonderful Universal Principles and
How We Got Them
History Lesson:
• The Three Wonderful Universal Principles and
How We Got Them
• Respect for Persons
• Beneficence
• Justice
• (Not to mention Integrity and Honesty)
Classic Historical Examples of the
Violation of All of the Above
• Nazi Doctors in Concentration Camps
• Tuskegee Syphilis Study - and Guatemala too!! 40's 70's
• http://en.wikipedia.org/wiki/Unethical_human_experi
mentation_in_the_United_States
• Responses
– Nuremberg Trials/Code - 1946-47 - voluntary participation,
animals first, discontinue if harms to human subjects
– Helsinki Declaration - 1964-2000 - Independent review
required, qualifications required
– Belmont Report - 1979- defining informed consent, noting
ward patients were guinea pigs, private patients were
beneficiaries – what principle is that again? _________
OK, this was bad. Really, Really Bad.
So now…
• All research must be approved by an IRB, and the
IRB decides if your proposal is minimal risk, deidentified and confidential enough to be exempt.
• It's actually quite a bit harder to do research with
special populations now.
• All researchers must be trained in ethics. (There
are really nice online programs to get this done
efficiently so you can get back to trying to write
grants and get published.)
What’s with all the hoops we have to jump
through, and who’s holding them??
• Overheard in 1980-something re research on
institutionalized kids: "I like to think...they're
giving something back.“
• Title 45, Part 46 - Code of Federal Regulations
(aka 45 CFR 46, The Protection of Human
Subjects Regulations)
– Outlines purpose and policies of Institutional Review
Board (IRB)
– Informed consent and protections for children,
pregnant women, fetuses, prisoners, and mentally
incompetent individuals.
How far should you go with informed
consent?
• Comprehensive (ALL risks and benefits), voluntary, and
competent
• Pretty far – PGP had an online exam you have to ace before
participation considered, including an essay question
• Case from UW site:
– Q: Mrs. Franklin, an 81-year-old Alzheimer's patient hospitalized
under your care has been asked to participate in a clinical trial
testing a new drug designed to help improve memory. You were
present when the clinical investigator obtained a signed
informed consent from Mrs. Franklin a few days ago. However,
when you visit Mrs. Franklin today and ask her if she is ready to
begin the study tomorrow, she looks at you blankly and seems
to have no idea what you are talking about.
– Now what?
• Q: Mrs. Franklin, an 81-year-old Alzheimer's patient hospitalized
under your care has been asked to participate in a clinical trial
testing a new drug designed to help improve memory. You were
present when the clinical investigator obtained a signed informed
consent from Mrs. Franklin a few days ago. However, when you visit
Mrs. Franklin today and ask her if she is ready to begin the study
tomorrow, she looks at you blankly and seems to have no idea what
you are talking about.
• A: The competence of Mrs. Franklin to give an ethically valid
informed consent is in doubt. You should contact the primary
investigator to discuss Mrs. Franklin's participation in the trial.
There may be a surrogate who can give consent for her
participation if it is deemed to be in her best interests. Although she
may be considered a vulnerable research subject because of her
mental status, Mrs. Franklin does belong to the population the
intervention is designed to assist, and her participation may benefit
herself and other Alzheimer's patients. However, a careful balancing
of risks and benefits should occur.
Another one from UW
• Q: After having completed a study that
involved the collection of tissue from the
subjects, an investigator wishes to perform
additional analysis of the archived tissue
samples. This nature of this analysis was not
explicitly stated in the original consent form.
Should the investigator be required to obtain
explicit consent for the new research? [And,
can you do a better job with the original
consent in the future?]
• Q: After having completed a study that involved the
collection of tissue from the subjects, an investigator
wishes to perform additional analysis of the archived
tissue samples. This nature of this analysis was not
explicitly stated in the original consent form. Should
the investigator be required to obtain explicit consent
for the new research?
• A: Institutional Review Boards have increasingly
required that explicit consent be obtained, if practical,
before archived tissue can used for research. Archiving
samples for an unspecified “future use” without
explicit consent undermines the autonomy of the
participants. Even if participants may be willing in
general to have surplus tissue used for research
purposes, they should still be asked for their consent.
A Powerful Question
• Q: You have limited funds and can just barely
cover enrolment of enough subjects to
adequately power your study. Can you
explicitly require that subjects may not
withdraw consent or have their data removed
from the study database once they have
provided the initial blood test sample and
received results?
• Q: You have limited funds and can just barely
cover enrolment of enough subjects to
adequately power your study. Can you explicitly
require that subjects may not withdraw consent
or have their data removed from the study
database once they have provided the initial
blood test sample and received results?
• A: Well, no. As in nope, no way, uh-uh, forget it.
If for any reason it would be impossible to do so,
you are obligated to say so up front as well.
Academic Dishonesty and The
Pressure to Publish
• With proper attribution built right in: barney-tobey-too-bad-about-oldainsworth-published-and-published-but-perished-all-th--new-yorkercartoon.jpg….BAD QOTD: “they can’t judge quality but they CAN count.”
Axes To Grind Should Be Left Behind
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Fabrication of Data
Plagiarism
Conflict of Interest
Phony/Honorary Authorship
Unpublished Negative Results
Misleading Lay Press Reports and Overinterpretation/Extrapolation
– Example: Dr. Andrew Wakefield,
http://www.theglobeandmail.com/life/parenting/youngchildren/children-health/article1867998.ece
Authorship
• One of the female pediatric physiatrists is
desperate to get published and says, “Sure,
you can come do research on my clinic
patients – as long as you put my name on the
paper!”
• What if it’s the Dept. head instead?
• And he is a successful current NIH grant
holder?
Sure, you can be a co-author…
• Make substantial contributions AND
– conception and design and/or
– acquisition of data and/or
– analysis and interpretation
• Write or revise all or part or the article AND
• Approve the final version of the entire article.
• Acquisition of funding, collection of data, or
general supervision of the research group, do not
justify authorship [but may merit at least a nice
acknowledgement.]
– guidelines from www.icmje.org
Ethics, Validity, and Applicability
• Piper and Pless
• The Anti-Antioxidant Paper
• LESS research on this subject is urgently needed…
– the worse disease is bad for you and costs more
syndrome , unless validating a clinical scale
– which is better versus what works for some if not all
• Clinical practice versus research
– What’s different between being a patient and being a
subject? What’s the same?
– What can you say to a patient who thinks you are
making them your guinea pig?
Assessing the Literature
• What does the author conclude?
• Do they present valid evidence for it?
– If not, what CAN they validly conclude ? (the
sympathetic reviewer’s question”)
• Does it apply to my patient(s)?
• Do others asking the same thing come up
with the same answers? If not, why??
• (How) Do I need to change my practice?
Additional Routes to Meaningful
Research and Best Practice
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Inform of off-label use of anything
Clinical Trials Registration
COI Disclosure
Consider community-based participatory
research
• http://www.achri.archildrens.org/resources
/research_resources.htm
• http://www.uams.edu/rsc/Resources.htm