Transcript RESEARCH ETHICS - UCLA CTSI | Accelerating Discoveries

Responsible Conduct of Research
Involving Humans

Stan Korenman, M.D.


Professor of Medicine
Associate Dean, Ethics
http://www.ctsi.ucla.edu/education/training/webcastsm261
What is Science?

Science is the systematic study of nature.
– It involves all of nature and all the tools we
use to study nature

Systematic study means the use of the
scientific method
A Picture of the Corpus of Science
An advance
A Paradigm Shift
An advance
What Is the Scientific Method ?
Hypothesis directed ….or is it?
 Experiments …. or observations
 Conclusions tentative
 Educated skepticism. “Prove it”
 Each report contributes to the body
 Each scientist is ethically responsible to
preserve and enhance the body of science

Science As A Problem
1. Dangers
Nuclear Energy
Energy consumption Global warming
Chemicals-CFCs, PCBs, Bisphenol A,
Safety of transgenic plants and animals
2. Research Misconduct
3. Risks and Misuse of Human Research
4. Ever Changing Conclusions
Responsibilities Of Science
1. Reason is the instrument of societal development,
and scientific investigation may be the ultimate
expression of human reason.
2. The public supports science to better understand
nature and help humanity.
3. Society’s increasing dependence on scientific
inquiry for advances and for policymaking,
conveys on science a great responsibility to
maintain its integrity.
4. Thus, in carrying out its public trust, science
operates in the realm of human duty i.e. in ethics.
Definition of Ethics

The science of morals; the department of
study concerned with the principles of
human duty.

EMERSON Nature, Idealism Wks. (Bohn)
II. 164 Ethics and religion differ herein; that
the one is the system of human duties
commencing from man; the other, from God
Oxford Dictionary
Sources of Duties –
What We Ought to Do

Not from:
–
–
–
–
–
Pressure groups
Professional organizations
Public opinion
The law
Religion
– We derive our oughts from within. What does
that mean?
Ethics: Study of Moral Behavior
1.CONSEQUENTIALIST ETHICSVarious forms of Utilitarianism;
The act is unimportant – look for greatest good in
the outcome
Making the utilitarian judgment for each act is hard
work – essentially impossible
To make decisions easier, create rules.
Rules comparing goods and greatest goods often lead to
injustices as well as irreconcilable differences of opinion.
What is a life really worth?
2. DEONTOLOGICAL ETHICS
We know instinctively what’s right- hard-wired
Absolute rules like ten commandments,
but values are cultural and change over time, so must
rules (behaviors towards women, minorities, and sexual preference)
Conflicting rules, legal and moral
“Golden Rule” operates for every act
TO MAKE THIS WORK OUT LOTS OF RIGHTS ARE DEFINED
Life, liberty, property
Autonomy, beneficence, justice, privacy
Obligations to others. (fiduciary roles)
You can’t put a value on a life.

3. Virtue ethics
Central concern is the life we live, to be a good person
Choices influenced by what will develop us as good
persons rather than be a slave to hard rules.
Behavioral principles can have legitimate exceptions
– Very susceptible to rationalization
Ethical Dilemma



Mary and Jody are conjoined twins. They,
together have one heart and one pair of
lungs. Surgery will permit Jody to survive
and be reasonably normal while Mary must
die. Without surgery, both will die in a
month or so
CONSEQUENTIALISTS
Operate
DEONTOLOGISTS - Let them both die
because you must not violate the principle
“Thou shall not kill”

Virtue – There can be exceptions to the
biblical rule
Is It Wrong to Use Unneeded Frozen
Embryos As Research Tools
Deontological argument: This is living
human tissue with the potential to be a
person- don’t mess with it.
 Utilitarian argument: These blastocysts
have zero chance of becoming a person and
using them may result in a lot of good for a
large number - use them.


These people are talking past each other.
Decisions Under Uncertainty
Expected Utility
Theory
 Rational decisions
under uncertainty are
made by estimating
the value of the
choices and picking
the option with the
greatest value.

Prospect Theory
Prospect Theory
David Hume
Decisions are powerfully
controlled by:
1. The initial condition.
2. Diminished sensitivity
to changes.
3. Loss-aversion
4. When all the choices
are bad, then risk
taking
Framing the “Decision Architecture”
Robert Cialdini: Influence; 6 Principles






Reciprocation
Consistency
Social Proof
Liking
Authority
Scarcity
Gifts
It’s Standard
Kobe does it
Really nice team
MD won’t harm me
Only a few places left
The End of Philosophy

In an op-ed piece in the
NY Times David Brooks
pronounced the end of
Philosophy because if our
decisions are based on
method of presentation
and outside influences,
then they can’t be called
rational decisions at all.
Plato
Do you agree with
this? Is there a
remedy?
Definition of Research Integrity

"Research integrity may be defined as
active adherence to the ethical principles
and professional standards essential for
the responsible practice of research."
Active Adherence
By active adherence we mean adoption of the
principles and practices as a personal credo, not
simply accepting them as impositions.
Principles
Honesty,
 The golden rule,
 Trustworthiness,
 High regard for the scientific record.
“While we encourage vigorous defense of
one’s ideas and work, ultimately research
integrity means examining the data with
objectivity and being guided by the results
rather than by preconceived notions.”

NAS Res Integrity
Practices
Honesty, fairness and proficiency in
1. proposing, performing, and reporting research
2. representing contributions to research proposals and
reports
3. peer review
Collegiality in scientific interactions,
communications and sharing of resources
Avoidance and disclosure of conflicts of interest
Protection of human subjects
Humane care of animals
Adherence to the mutual responsibilities of
mentors and trainees
Responsible Conduct of Research

Social responsibility

Performance

Reporting

Mentoring

Communication
Conflicts of interest

Pope John Paul II,
The preeminence of the profit motive in
conducting scientific research ultimately means
that science is deprived of its epistemological
character, according to which its primary goal
is discovery of the truth. The risk is that when
research takes a utilitarian turn, its speculative
dimension, which is the inner dynamic of man’s
intellectual journey, will be diminished or
stifled.
3/25/02
Social Responsibility
Do science and scientists have ethical
responsibilities to society beyond
discovering truths and problem-solving?
 Do they have a responsibility to report
results, however negative the predictable
consequences.
 Do they have an ethical responsibility to
defend science (intelligent design)

Social Responsibility
“We make it possible and others use it for
good or evil.”
 Scientists must be involved in the
consequences of their work.
 Nuclear fission, Internet, Cloning,
Medicine, Ecology, Sociology
 Can’t predict the consequences of
discoveries and inventions (invention of the

computer)
Responsible Performance
A. Experimental design is most critical
1. Openness
2. Adequate controls
3. Objective end points
4. Proper analytic tools used properly
We now have (brute force biology), a different design
B. Complete and accessible records
Privacy and security (think huge databases)
C. Play by the rules
Human and animal subjects, OSHA, Radiation Safety,
HIPAA, etc.
Ownership of Data
Data include any information obtained during the
process of research, no matter in what form it
is produced, or in what form it is stored.
Medical information - belongs to the research
participant and must be protected for privacy
Research – University owns it and shares with PI
Drug studies- by the sponsor and the institution
Trainees own no data, not even what they worked
on
NIH Rules on Sharing




NIH reaffirms its support for data sharing, believing
that it is essential for expedited exploitation of research
results.
Timely release and sharing of the final research data
from NIH-supported studies for use by other
researchers.
Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are
required to include a plan for data-sharing or state why
data sharing is not possible.
“The timely release of information” must be no later
than the acceptance for publication of the main findings
from the final data set.
Responsible Reporting
A. Full attribution and citation of sources
B. Relevant data included or absence
explained
C. Technical information for replication
included or available online.
D. Authors all contributing and responsible
(in their own domain).
E. Data reported only once as original work
Authors All Contributing And
Responsible
GOOD STUFF
 Initial idea
 Research plan
 Regular review
 Doing the work
 Analyzing results
 Writing it up
LESS IMPORTANT
 Provides funding
 Provides probes, cells,
transgenics, clones
 Occasional advice
 Does an assay
 Paper once-over
First authorship requires both major work and major
writing
Rules for Publishing Clinical
Trials in Major Journals

Registration at inception

Disclosure of all author conflicts of interest to
institution, participants, editors

Roles of sponsor and investigators in the experimental
design, collection, analysis, and interpretation of data,
and of writing of the report

Grassley
Determination that the authors had full access to the
data
Your Other Job, Peer Review
Review of:
They require:
Grants
Publications
Appointments
Promotions
IRB submissions
ESCRO proposals
RAC submissions
Data monitoring
Objective review
Expert assessment
Openness to innovation
Withdrawal if possible
conflict of interest
Absolute confidentiality
Responsible Communication

The most difficult situations between scientists
are due to failure to communicate, sometimes
accidental, sometimes deliberate. The rupture
of trust usually cannot be repaired, to
everyone’s disadvantage.

Terms of collaboration
Sharing of resources
Patent and licensure
Authorship
Interpretation and reporting of results




Collaboration is almost universal in human research.
Mentoring

The job of the mentor is to facilitate the success
of the trainee. If you don’t believe that, then
don’t take on trainees.
– (Trainees, try to find a mentor who cares about your success.)

Explicit moral climate. We do science right!
– The research team needs ethical guidance from its
leaders


Enthusiasm for innovation and failures. What
can we learn? rather than, you made a mistake!
Openness. You can talk about your work.
Explicit guidelines for records, data
Academic Mentoring




Three years ago UCLA developed a mentoring
program that has been very successful in moving
the youngest faculty up the ladder.
They help with going through the promotion
process, negotiations, and general career advice.
Advisors are from different departments than the
faculty and can be objective.
www.faculty.diversity.ucla.edu
Irresponsible Conduct of Research

Social responsibility


Performance




Reporting
Mentoring

Communication


Conflicts of interest


Proposing research to
degrade others
Fabrication,
falsification
Plagiarism
Exploiting, abusing
trainees
Secrecy
Failure to disclose
Unethical Research?
When Southam began injecting people
with HeLa cells in 1954 there was no
formal research oversight in the US.
Since the turn of the century,
politicians had been introducing state
and federal laws with hopes of
regulating human experimentation, but
physicians and researchers always
protested. The bills were repeatedly
voted down for fear of interfering with
the progress of science, even though
other countries –had enacted
regulations as early as 1891.
What would have happened with
Henrietta’s cells if informed consent
were required?