PowerPoint Presentation (PDF) - Perfusion.com

David S Edgell, BA, MHSc, CCP, CPC
SickKids, Labatt Family Heart Centre
Toronto, Ontario, Canada
Acknowledgement:
Christine Harrison, Director of Bioethics, SickKids,
Richard Sugarman ,Chair Research Ethics Board
Bob Groom, JECT, Editor in Chief
www.preservationhall.com

Opening Thought
“An experiment is ethical or not at its
If inception; a study is it unethical does not to become start with, ethical it
does post not hoc become – ends do ethical not justify because the it
produces means. There useful is results. no ethical distinction
between ends and means.”
Ethics and clinical research
Henry Beecher, 1966, NEJM Vol.274,24,367 -372

Objectives
• Improve understanding of ethical research.
• Describe the “Gelsinger”case and
publications that illustrate the impact of
unethical research.
• Review Research Ethics references in
AmSECT documents and benchmark
journals.
• Show that written standards are not enough.
• Suggest improving Research Ethics
education for Perfusionists.

Modern era in research ethics
• 1931 directive German Reich Minister of the
Interior
• Forbids “innovative therapy” unless the
“subject or his legal representative has
unambiguously consented to the
procedure in the light of relevant
information provided in advance”

Nuremberg Code – 1947
•“Doctors’ Trial”, post
W.W.II war crimes
tribunal
•Response to
research atrocities
•Deliberate
infection with
malaria, smallpox,
cholera
•Sexual sterilization
experiments
•Cold temperature
experiments
www.nuernberg.de/.../doctors_trial.html Downloaded March 2011

HHS Policy for Protection of Human Research Subjects
Code of Federal Regulations
DEPARTMENT OF HEALTH AND HUMAN SERVICES PART 46 Revised January 15, 2009
• In order to approve research covered by this policy the
IRB shall determine that all of the following
requirements are satisfied:
• Risks to subjects are minimized
• Risks to subjects are reasonable in relation to
anticipated benefits, if any, to subjects, and the
importance of the knowledge that may reasonably be
expected to result.
• Selection of subjects is equitable.
• Informed consent will be sought from each prospective
subject or the subject's legally authorized representative,
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.111

A good place to start!
For help writing a
research protocol
http:www.cc.nih.gov/cc/proto
mechanics/index.html
For studies with complex
ethics or regulatory
considerations contact
your IRB Chair
OHSR (301-402-3444)
The clinical Center’s
Department of Bioethics
(301– 496-2429)
This booklet is available from NIH
50 copies will be at the Ethics Committee table at the
AmSECT Committee Fair this Saturday

What does our professional society
say about research?
• Code of Ethics
• Maintain and promote high standards for perfusion
practice which may include education, research and
scientific presentations and/or publications.
• Protect the rights of patients and animals involved in
research and conduct research in accordance with
accepted ethical and reporting standards.
• AmSECT Role Document
• Quality Improvement framework
• … clinical evaluations and documented clinical and
scientific data.
• … not compromised by gratuities, gifts,
entertainment, consulting engagements, employment
status, or any other material or personal gain.
www.amsect.org

Perfusion projects lend themselves
to Quality Improvement initiatives.
• QI is designed to bring about immediate
improvements in healthcare delivery.
• QI is designed to have its findings applicable
only to the local institution.
• QI is designed to sustain the improvements.
• QI does not require rigid, fixed protocols;
• Within QI activities it is acceptable to adapt the
project over time.
• May be publishable in QI journals

When does it become research?
•Research is defined as “a systematic
investigation, including development,
testing, and evaluation, designed to
develop or contribute to generalisable
knowledge.”

When Do I Require Ethics Approval?
•If you plan to conduct research that
involves human subjects, you are
required to seek, and receive, ethics
approval from the appropriate research
ethics board/committee before
proceeding with your study.
http://comcul.ucalgary.ca/approval

Where does the scientific community stand with respect
to adherence to the concepts of research ethics?
ORI - US dept of Health and Human Services
Benos DJ et al, Advan Physiol Educ 29:59-74,2004

Scientific Misconduct takes various forms.
Benos DJ et al, Advan Physiol Educ 29:59-74,2004

A prime example in the current literature.
May 2011 • Volume 112 • Number 5 editorial
www.anesthesia-analgesia.org
• Notices of Retraction
• In 2009, Dr. Joachim Boldt published a manuscript in
Anesthesia & Analgesia - Comparing albumin and
hydroxyethyl starch priming cardiopulmonary bypass.
• “review determined that there was no IRB approval for the study. The article
was retracted in December 2010.”
• “Research without IRB approval is a violation of human rights. As described in
Guide for Authors,26 and a recent editorial,27 Anesthesia & Analgesia requires
IRB approval for all human research. There are no exceptions.”
• “The 22 manuscripts published by Dr. Boldt for which IRB approval has not
been confirmed by LÄK-RLP are hereby retracted for unethical conduct of
research.”
• “103 additional manuscripts included Dr. Boldt as a coauthor”
http://www.anesthesia-analgesia.org/ Downloaded April 10, 2011

A significant proportion of journals still do not
demand statements of adherence to standards.
A comparison of journal instructions regarding institutional review board approval and conflict
of interest disclosure between 1995 and 2005, Rowan- Legg, J Med Ethics :35 74-78 ; 2009

What about our benchmark journals?
• Human investigation
• “Include the date of institutional review board or
human research committee approval, or the ethical
guidelines that were followed by the investigators
in the materials and methods section of the
manuscript.”
http://www.ject.org/sections/authorinstructions/index.html downloaded March 2011

What about our benchmark journals?
“When reporting experiments on
human subjects, indicate
whether the procedures followed
were in accordance with the
ethical standards of the
responsible committee on
human experimentation
(institutional or regional) or with
the Declaration of Helsinki 1975,
revised Hong Kong 1989.
http://www.uk.sagepub.com/repository/binaries/pdf/PRF_Manuscript_Guidelines.pdf#6.2
Downloaded March 2011

What is the Perfusionist’s role.
Time Magazine
April 2002
Although we may not have initiated the research, the projects of
others have an impact on us.
The public expects that we are knowledgeable and attentive with
respect to their rights.

Case from the literature
“Gene Therapy Under Scrutiny
Experts Suggest Tougher Controls”
18-year-old Jessie Gelsinger, volunteered to be part of a study
conducted at the University of Pennsylvania.
He had a rare metabolic disease, ornithine transcarbamylase
deficiency, which prevents the body from properly
processing nitrogen.
The disease is usually fatal at birth, but Gelsinger had not
inherited the disease; in his case it was the result of a
genetic mutation and as such was not as severe - some of
his cells were normal which enabled him to survive on a
restricted diet and special medications.
http://www.cbsnews.com/stories/1999/12/08/broadcasts/main57783.shtml

A failure to adhere to research ethics.
• Gelsinger was injected with an adenoviral vector carrying a
corrected gene to test the safety of the procedure.
• An (FDA) investigation concluded that the scientists
involved in the trial, broke several rules of conduct:
• Inclusion of Gelsinger as a substitute for another
volunteer who dropped out, despite having high
ammonia levels that should have led to his exclusion
from the trial
• Failure by the university to report that two patients had
experienced serious side effects from the gene therapy
• Failure to mention the deaths of monkeys given a similar
treatment in the informed consent documentation.

What has this got to do with Perfusion?
Jesse’s last hours according to his father
• 10:30
• 3:00
• 5:00
• 12:00
• 8:00 AM
Respiratory failure on the ventilator resulted in
ECMO being requested.
“It seemed to take forever for them even to get
an artificial lung ready.”
“Dr. S came to see me and said the ECMO had a
major leak and Dr. R had his finger on the leak.
I quipped that I was a plumber , maybe that’s
what they needed.”
“More than 10 units of blood used in hooking
him up. When we finally got to see Jesse he was
bloated beyond all recognition. His eyes were
swelled shut and the wax was being extruded
out of his ears.”
Next day - Jesse died

Impact
All medical research
has been affected.
1981 - 1999
• The University of Pennsylvania paid the parents an
undisclosed amount in settlement.
• Both the PI and the University are reported to have
had financial stakes in the research.
• The Gelsinger case was a severe setback for scientists
working in the field.

Heart Ache
• “We are just research subjects in an enormous
marketplace, manipulated into believing the hype and
vision of the very ambitious. That ambition is blinding
not only the innocent but also those so tied up in the
endeavors of modern science that they have no hope of
really seeing the right path to the truth.”
• Paul Gelsinger on the death of his son
Uninformed consent: The Case of Jesse Gelsinger by Paul
Gelsinger in Law and Ethics in Biomedical Research, edited
by Lemmens and Waring, U of T Press, 2006

Conclusion
•Historically Perfusionists have focused
their attention on clinical practice but
they have used research methods to
advance their knowledge base.
•Research ethics and its processes are
not meant to hinder research but to
ensure that good research is
undertaken.

Conclusion
•Ethical research practices are essential
for Perfusionists as we continue to
assume our potential as respected
health professionals working as valued
members of an interdisciplinary team.
•Research Ethics education should be a
strategic objective of AmSECT.