Transcript Clinical Investigator’s Program:Why Research Ethics Matter

Clinical Investigator’s Program:
Why Research Ethics Matter
Michelle A. Mullen
University of Ottawa Departments of
Paediatrics & Women’s Studies
Bioethicist, CHEO
Clinical Research: an ethical enterprise
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Cancer Rx
Transplantation
Infectious Diseases
Cardiovascular Care
Genetics
Goals…
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Walk in the hall of ignomy
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Lessons to be learned?
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Why ethics matters…
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Good Science & Good Ethics
– take home messages
Dr. Roger Poisson 1994
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Falsified data in groundbreaking lumpectomy vs.
mastectomy cohort
Claimed he was trying to do the
best for his patients: conflated
clinician and researcher roles
FDA ban from any access to
U.S. funds and disciplined by
his professional college
Lessons…?
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FDA disqualified Poisson from grants process after
he acknowledged falsifying results of other studies
ORI found “115 well-documented instances of data
fabrication”
Investigators must continually remember when they
are acting as researchers and when they are acting as
clinicians. Investigators need adequate training as
scientists.
A colleague described Poisson as a “proud man-proud
to say that he puts most of his patients in trials,
proud to get grants, proud to get his name on
research papers”
Dr. Nancy Olivieri 1998
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Dr. Olivieri wanted to tell research
subjects and the scientific community
of potential (lethal) risks with the drug
(deferiprone) that children in a clinical
trial were taking as experimental
treatment for thalassaemia
The manufacturer of the drug ordered
her not to disclose these findings to
participants or researchers
Public and protracted conflict
Lessons…?
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Institutions need to adopt AND enforce
strict conflict of interest polices
Institutions and REBs need to review
contracts
Confidentiality clauses that potentially
restrict informing either participants or the
scientific community are unacceptable (timelimited notification clause)
Clinician investigators need to understand
their obligations, rights, responsibilities prior
to undertaking clinical research
Mr. Gabriel Lessard
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In 1991 Lessard volunteered to take
part in a study to screen for
prostate cancer
The next year researchers found a
slight abnormality but decided the
result wasn't important and chose
not to tell Lessard
In 1993, researchers did another
test, with abnormal results but it
was too late, the cancer too invasive
Lessons…?
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Quebec coroner Luc Malouin says researchers
put medicine on the back seat
"The doctor has the obligation to give the
truth to the patient"
Standards for clinical disclosure (Reibl v
Hughes SCC) are higher in the research
context
Consent, disclosure of pertinent/unexpected
findings, disemmination of research results
should be considered a priori
Ryan 2002
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4 year old child died at the
Children's Hospital of
Eastern Ontario after he
was given a "significant
overdose" (25X) of an
experimental drug
(Interleukin II) for
‘treatment’ of NB
CHEO has been praised for
its transparent approach in
handling this issue
Lessons…?
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FDA inspection; letter to trial physician
posted on web site
Previous OD and toxicity reported, not taken
account of – safety and monitoring
HC did not undertake separate investigation,
but notified research centres, drug
companies, REBs and hospitals across Canada
that adherence with regulations “is
obligatory”
Mistakes happen on clinical trials -
Jesse Gelsinger
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18 yo first patient to die in
clinical trials for gene therapy
OTC (ornithine transcabamylase)
deficiency, usually fatal at birth
-some normal cells enabled him
to survive with diet / meds
Sept/99 Jesse injected with
adenovirus carrying a corrected
gene
died four days later (massive
immune response with multiple
organ failure and brain death)
Lessons…?
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FDA concluded scientists involved in the trial
broke several rules of conduct:
Inclusion of Gelsinger as a substitute for another
volunteer, despite having high ammonia levels that
should have led to his exclusion
Failure by the university to report that two
patients had experienced serious side effects
from the gene therapy
Failure to disclose the deaths of monkeys given a
similar treatment in the informed consent
documentation.
The University of Pennsylvania later issued a
rebuttal, but paid the parents an undisclosed
amount in settlement
Why ethics matters…
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Why do patients come to us?
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Who benefits from clinical research?
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Who pays for research?
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Starting research process from ethical
viewpoint…
Good Science & Good Ethics needed
Good Science & Good Ethics
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Equipoise
Roles/dual agency
Disclosure
 risks & benefits
 conflict of interest
 unexpected results
 recruitment
(vulnerable populations)
Safety & Monitoring
Regulations
Even if I don't
finish, we need
others to continue.
It's got to keep
going without me.
Terry Fox