responsible conduct of research involving humans
TRANSCRIPT
Responsible Conduct of Research
Involving Humans
Stan Korenman, M.D.
Professor of Medicine
Associate Dean, Ethics
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?
Unethical Research?
M261: Responsible Conduct of
Clinical and Translational Research
Sep 28 Introduction to Research Ethics Stan Korenman
Oct 5 Professionalism and the Ethical Imperatives of Clinical Research
Neil Wenger
Oct 12 Protection of Research Subjects, the IRB process Sharon Friend
Oct 19 Research Facilitation and Oversight Laurie Shaker-Irwin
Intellectual Property and Technology Transfer Emily Loughran
Oct 26 Issues in Stem Cell Research Steve Peckman
Nov 2 Genetics and Stem Cell Research Leslie Raffel
Nov 9 Responsible Conduct of Community and International Research
Roger Detels
Nov 16 Malfeasance and Misconduct Stan Korenman,Tom Kosakowski
Nov 23 Pre Thanksgiving Holiday
Nov 30 Conflicts of Interest: Stan Korenman, Ann Pollack
Receive Exam
Receive Exam
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 corpus
Each scientist is ethically responsible to
preserve and enhance the corpus
Science As A Problem
1. Dangers Nuclear Energy
Global warming
Chemicals-CFCs, PCBs, Bisphenol A,
Safety of transgenic plants and animals
Violations of Privacy and confidentiality
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
Ethics: Study of Moral Behavior
1) CONSEQUENTIALIST ETHICS-
Various forms of Utilitarianism;
The act is unimportant – look for greatest good in
the outcome
Making the utilitarian judgement 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
Rules like ten commandments,
but values are cultural and change over time, so must rules behaviors towards women and minorities
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, privacy, justice
Obligations to others.
You can’t put a value on a life.
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
What to do?
CONSEQUENTIALISTS Operate
DEONTOLOGISTS - Let them both die
because you must not violate the principle
“Thou shall not kill”
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.
Rational Decision-making
Behavioral psychologists have learned a
great deal about human preferences and
decision-making
Even what we think of as carefully
considered rational decisions are influenced
by external factors.
Framing the “Decision Architecture” of
choice opportunities greatly influences the
outcome.
Compliance Professionals
Robert Cialdini: Influence; 6 Principles
Reciprocation Gifts
Consistency It’s Standard
Social Proof Kobe does it
Liking Really nice team
Authority MD won’t harm me
Scarcity Don’t miss out
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.
Do you agree with this? Is there a remedy?
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
Research Integrity
Research integrity is essential for achieving
scientific excellence and for earning the public's
trust.
Integrity embodies above all an individual
scientist’s commitment to intellectual honesty and
personal responsibility and an institution's
commitment to maintaining an environment that
promotes responsible conduct.
Civilized vs survivalist behavior.
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
Social Responsibility
Do science and scientists have ethical
responsibilities to society beyond
discovering truths and developing
solutions to problems?
Do they have a responsibility to report
results, whatever the predicted
consequences.
Do they have an ethical responsibility to
defend science (against intelligent design)
Responsible Conduct of Research
Social responsibility
Performance
Reporting
Mentoring
Communication
Conflicts of interest
Social Responsibility
“We make it possible and politicians use it
for good or evil.”
Scientists must be involved in the
consequences of science and technology.
Nuclear fission, Internet, Genomics,
Cloning, Medicine, Ecology, Sociology
Can’t predict the consequences of
discoveries and inventions
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 sometimes the
investigator
Trainees own no data, not even what they worked
on
Types Of Research
Exploratory
Small experiments
Few controls
Frequent changes of conditions
Multiple systems
Prepare for definitive study
Definitive
Large experiments
Comprehensive
controls
Optimized conditions
One system
Publish
brute force biology and observational studies have different
designs.
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:
Grants
Publications
Appointments
Promotions
IRB submissions
SCRO submissions
RAC submissions
Data monitoring
Require:
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
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!
– Science needs ethical guidance from 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
management, authorship
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