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