Ethics in Patient-Oriented Research n Stan Korenman, M.D. n Professor of Medicine n Associate Dean, Ethics.

Ethics in Patient-Oriented ResearchEthics in Patient-Oriented Research

Stan Korenman, M.D.Stan Korenman, M.D.

Professor of Medicine Professor of Medicine Associate Dean, EthicsAssociate Dean, Ethics

M261: Responsible Conduct of M261: Responsible Conduct of Clinical and Translational ResearchClinical and Translational Research

Sep 29 Introduction to Research Ethics Stan KorenmanSep 29 Introduction to Research Ethics Stan Korenman The responsibilities of Institutions Ann Pollack   The responsibilities of Institutions Ann Pollack   Oct 6 Professionalism and the Ethical Imperatives of Clinical Research Oct 6 Professionalism and the Ethical Imperatives of Clinical Research

Neil Wenger Neil WengerOct 13 Protection of Research Subjects IRB Sharon FriendOct 13 Protection of Research Subjects IRB Sharon FriendOct 20 Research Monitoring Laurie Shaker-Irwin Oct 20 Research Monitoring Laurie Shaker-Irwin Technology Transfer Kathryn Atchison Technology Transfer Kathryn Atchison

Oct 27 Genetics and Stem Cell Researc Leslie Raffel Oct 27 Genetics and Stem Cell Researc Leslie Raffel Nov 3 Responsible Conduct of Community and International ResearchNov 3 Responsible Conduct of Community and International Research Roger Detels Roger Detels Nov 10 Privacy and Confidentiality TBNNov 10 Privacy and Confidentiality TBNNov 17 Malfeasance and Misconduct Stan Korenman, Nov 17 Malfeasance and Misconduct Stan Korenman, Ombuds Tom KosakowskiOmbuds Tom KosakowskiNov 24 Pre Thanksgiving HolidayNov 24 Pre Thanksgiving HolidayDec 1 Conflicts of Interest: Built-in Bias.    Stan KorenmanDec 1 Conflicts of Interest: Built-in Bias.    Stan Korenman

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What is Science?What is Science?

Science is the systematic study of nature.Science is the systematic study of nature.– It involves all of nature and all the tools we It involves all of nature and all the tools we

useuse to study natureto study nature Systematic study means the use of the Systematic study means the use of the

scientific methodscientific method

A Picture of the Corpus of Science

An advance

A Paradigm Shift

An advance

What Is the Scientific Method ?What Is the Scientific Method ?

Hypothesis directed ….or is it? Hypothesis directed ….or is it? Experiments …. or observationsExperiments …. or observations Conclusions tentativeConclusions tentative Educated skepticism. “Prove it”Educated skepticism. “Prove it” Each report contributes to the corpus Each report contributes to the corpus Each scientist is ethically responsible to Each scientist is ethically responsible to

preserve and enhance the corpuspreserve and enhance the corpus

Science As A ProblemScience As A Problem

1. 1. DangersDangersNuclear EnergyNuclear Energy

Global warmingGlobal warming

Chemicals-CFCs, PCBs, Bisphenol A, Chemicals-CFCs, PCBs, Bisphenol A,

Safety of transgenic plants and animalsSafety of transgenic plants and animals

Violations of Privacy and confidentiality Violations of Privacy and confidentiality

2.2. Research Research MisconductMisconduct

3. Risks and Misuse of Human Research3. Risks and Misuse of Human Research

4. Ever Changing Conclusions4. Ever Changing Conclusions

Responsibilities Of ScienceResponsibilities Of Science

1. Reason is the instrument of societal development, 1. Reason is the instrument of societal development, and scientific investigation may be the ultimate and scientific investigation may be the ultimate expression of human reason.expression of human reason.

2. The public supports science to better understand 2. The public supports science to better understand nature and help humanity. nature and help humanity.

3. Society’s increasing dependence on scientific 3. Society’s increasing dependence on scientific inquiry for advances and for policymaking, inquiry for advances and for policymaking, conveys on science a great responsibility to conveys on science a great responsibility to maintain its integrity. maintain its integrity.

4. Thus, in carrying out its public trust, science 4. Thus, in carrying out its public trust, science operates in the realm of human duty i.e. in ethics. operates in the realm of human duty i.e. in ethics.

Definition of EthicsDefinition of Ethics

The science of morals; the department of The science of morals; the department of study concerned with the principles of study concerned with the principles of human duty.human duty.

EMERSONEMERSON Nature, IdealismNature, Idealism Wks. (Bohn) Wks. (Bohn) II. 164 Ethics and religion differ herein; that II. 164 Ethics and religion differ herein; that the one is the system of human duties the one is the system of human duties commencing from man; the other, from commencing from man; the other, from GodGod

Oxford Dictionary

Ethics: 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?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, propertyAutonomy, privacy, justiceObligations to others.You can’t put a value on a life.You can’t put a value on a life.

Ethical DilemmaEthical 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 Is It Wrong to Use Unneeded Frozen Embryos As Research ToolsEmbryos As Research Tools

Deontological argumentDeontological argument: This is living : This is living human tissue with the potential to be a human tissue with the potential to be a person- don’t mess with it.person- don’t mess with it.

Utilitarian argumentUtilitarian argument: These blastocysts : These blastocysts have zero chance of becoming a person and have zero chance of becoming a person and using them may result in a lot of good for a using them may result in a lot of good for a large number - use them.large number - use them.

These people are talking past each other.These people are talking past each other.

Rational Decision-makingRational Decision-making

Behavioral psychologists have learned a Behavioral psychologists have learned a great deal about human preferences and great deal about human preferences and decision-making decision-making

Even what we think of as carefully Even what we think of as carefully considered rational decisions are influenced considered rational decisions are influenced by external factors.by external factors.

Framing the “Decision Architecture” of Framing the “Decision Architecture” of choice opportunities greatly influences the choice opportunities greatly influences the outcome.outcome.

Compliance ProfessionalsCompliance Professionals

Robert Cialdini: Influence; 6 PrinciplesRobert Cialdini: Influence; 6 Principles Reciprocation Reciprocation Gifts Gifts ConsistencyConsistency It’s Standard It’s Standard

Social Proof Social Proof Kobe does it Kobe does it LikingLiking Really nice team Really nice team Authority MD won’t harm Authority MD won’t harm

me me

ScarcityScarcity Don’t miss out Don’t miss out

The End of PhilosophyThe End of Philosophy

In an op-ed piece in the NY Times David In an op-ed piece in the NY Times David Brooks pronounced the end of Philosophy Brooks pronounced the end of Philosophy because if our decisions are based on because if our decisions are based on method of presentation and outside method of presentation and outside influences, then they can’t be called rational influences, then they can’t be called rational decisions at all.decisions at all.

Do you agree with this? Is there a remedy?Do you agree with this? Is there a remedy?

Pope John Paul IIPope John Paul II,,

The preeminence of the profit motive in The preeminence of the profit motive in conducting scientific research ultimately means conducting scientific research ultimately means that science is deprived of its epistemological that science is deprived of its epistemological character, according to which its primary goal character, according to which its primary goal is discovery of the truth. The risk is that when is discovery of the truth. The risk is that when research takes a utilitarian turn, its speculative research takes a utilitarian turn, its speculative dimension, which is the inner dynamic of man’s dimension, which is the inner dynamic of man’s intellectual journey, will be diminished or intellectual journey, will be diminished or stifled.stifled.

3/25/023/25/02

Definition of Research IntegrityDefinition of Research Integrity

"Research integrity may be defined as "Research integrity may be defined as activeactive adherence to the ethical adherence to the ethical principles principles and and professional standardsprofessional standards essential for essential for the responsible practice of research."the responsible practice of research."

Active AdherenceActive Adherence

By active adherence we mean adoption of the principles and practices as a personal credo, not simply accepting them as impositions.

PrinciplesPrinciples

Honesty, Honesty, The golden rule, The golden rule, Trustworthiness, Trustworthiness, High regard for the scientific record. High regard for the scientific record. ““While we encourage vigorous defense of While we encourage vigorous defense of

one’s ideas and work, ultimately research one’s ideas and work, ultimately research integrity means examining the data with integrity means examining the data with objectivity and being guided by the results objectivity and being guided by the results rather than by preconceived notions.” rather than by preconceived notions.” NAS Res NAS Res IntegrityIntegrity

PracticesPractices

Honesty, fairness and proficiency in Honesty, fairness and proficiency in 1. proposing, performing, and reporting research1. proposing, performing, and reporting research2. 2. representing contributions to research proposals and representing contributions to research proposals and

reportsreports3. 3. peer reviewpeer review

Collegiality in scientific interactions, Collegiality in scientific interactions, communications and sharing of resourcescommunications and sharing of resources

Avoidance and disclosure of conflicts of interestAvoidance and disclosure of conflicts of interestProtection of human subjectsProtection of human subjectsHumane care of animalsHumane care of animalsAdherence to the mutual responsibilities of Adherence to the mutual responsibilities of

mentors and traineesmentors and trainees

Social ResponsibilitySocial Responsibility

Do science and scientists have ethical Do science and scientists have ethical responsibilities to society beyond responsibilities to society beyond discovering truths and developing discovering truths and developing solutions to problems?solutions to problems?

Do they have a responsibility to report Do they have a responsibility to report results, whatever the predicted results, whatever the predicted consequences.consequences.

Do they have an ethical responsibility to Do they have an ethical responsibility to defend science (defend science (Intelligent DesignIntelligent Design))

Responsible Conduct of ResearchResponsible Conduct of Research

Social responsibilitySocial responsibility

PerformancePerformance

ReportingReporting MentoringMentoring

CommunicationCommunication Conflicts of interestConflicts of interest

Social ResponsibilitySocial Responsibility

““We make it possible and politicians use it We make it possible and politicians use it for good or evil.”for good or evil.”

Scientists must be involved in social Scientists must be involved in social development derived from science and development derived from science and technology, health care reform, global technology, health care reform, global warming, pollution of the earth.warming, pollution of the earth.

Can’t predict the consequences of Can’t predict the consequences of discoveries and inventions discoveries and inventions

Nuclear fission, Internet, Genetics, Nuclear fission, Internet, Genetics, Cloning, Medicine, Ecology, SociologyCloning, Medicine, Ecology, Sociology

Responsible PerformanceResponsible Performance

A. Experimental design is most criticalA. Experimental design is most critical

1. Openness1. Openness

2. Adequate controls2. Adequate controls

3. Objective end points3. Objective end points

4. Criteria for rejecting data4. Criteria for rejecting data

We now have (We now have (brute force biology),brute force biology), a different design a different design

B. Complete and accessible recordsB. Complete and accessible records

Privacy and security Privacy and security (think huge databases)(think huge databases)

C. Play by the rulesC. Play by the rules

Human and animal subjects, OSHA, Radiation Safety, Human and animal subjects, OSHA, Radiation Safety, HIPAA, etc.HIPAA, etc.

Ownership of DataOwnership of Data

Data include any information obtained during the Data include any information obtained during the process of research, no matter in what form it process of research, no matter in what form it is produced, or in what form it is stored.is produced, or in what form it is stored.

Medical information - belongs to the research Medical information - belongs to the research participant and must be protected for privacyparticipant and must be protected for privacy

Grants – University owns it and shares with PIGrants – University owns it and shares with PI

Drug studies with the sponsor and sometimes the Drug studies with the sponsor and sometimes the investigator investigator

Trainees own no data, not even what they worked Trainees own no data, not even what they worked onon

NIH Rules on SharingNIH Rules on Sharing

NIH reaffirms its support for data sharing, believing NIH reaffirms its support for data sharing, believing that it is essential for expedited translation of research that it is essential for expedited translation of research results. results.

Timely release and sharing of the final research data Timely release and sharing of the final research data from NIH-supported studies for use by other from NIH-supported studies for use by other researchers. researchers.

Investigators submitting an NIH application seeking Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are $500,000 or more in direct costs in any single year are required to include required to include a plan for data-sharinga plan for data-sharing or state why or state why data sharing is not possible.data sharing is not possible.

““The timely release of information” must be no later The timely release of information” must be no later than the acceptance for publication of the main findings than the acceptance for publication of the main findings from the final data set.from the final data set.

Responsible ReportingResponsible Reporting

A. Full attribution and citation of sourcesA. Full attribution and citation of sources

B. Relevant data included or absence B. Relevant data included or absence explainedexplained

C. Technical information for replication C. Technical information for replication included or available online.included or available online.

D. Authors all contributing and responsibleD. Authors all contributing and responsible

(in their own domain).(in their own domain).

E. Data reported only once as original workE. Data reported only once as original work

Authors All Contributing And Authors All Contributing And ResponsibleResponsible

GOOD STUFFGOOD STUFF Initial ideaInitial idea Research planResearch plan Regular reviewRegular review Doing the workDoing the work Analyzing resultsAnalyzing results Writing it upWriting it up

LESS IMPORTANTLESS IMPORTANT Provides fundingProvides funding Provides probes, cells, Provides probes, cells,

transgenics, clonestransgenics, clones Occasional adviceOccasional advice Does an assayDoes an assay Paper once-overPaper once-over

First authorship requires both major work and major writing

Rules for Publishing Clinical Rules for Publishing Clinical Trials in Major JournalsTrials in Major Journals

Registration at inceptionRegistration at inception

Disclosure of all author conflicts of interest to Disclosure of all author conflicts of interest to

institution, participants, editorsinstitution, participants, editors

Roles of sponsor and investigators in the experimental Roles of sponsor and investigators in the experimental

design, collection, analysis, and interpretation of data, design, collection, analysis, and interpretation of data,

and of writing of the reportand of writing of the report GrassleyGrassley

Determination that the authors had full access to the Determination that the authors had full access to the

datadata

Your Other Job, Peer ReviewYour Other Job, Peer Review

Review of:Review of:Grants Grants

Publications Publications

AppointmentsAppointments

PromotionsPromotions

IRB submissions IRB submissions

SCRO submissionsSCRO submissions

RAC submissionsRAC submissions

Data monitoringData monitoring

Require:Require:

Objective reviewObjective review

Expert assessmentExpert assessment

Openness to innovationOpenness to innovation

Withdrawal if possible Withdrawal if possible conflict of interestconflict of interest

Absolute confidentialityAbsolute confidentiality

Responsible CommunicationResponsible Communication

The most difficult situations between scientists The most difficult situations between scientists are due to failure to communicate, sometimes are due to failure to communicate, sometimes accidental, sometimes deliberate. The rupture of accidental, sometimes deliberate. The rupture of trust between individuals or groups usually trust between individuals or groups usually cannot be repaired, to everyone’s disadvantage.cannot be repaired, to everyone’s disadvantage.

Terms of collaborationTerms of collaboration Sharing of resourcesSharing of resources Patent and licensurePatent and licensure AuthorshipAuthorship

MentoringMentoring

The job of the mentor is to facilitate the success The job of the mentor is to facilitate the success of the trainee. If you don’t believe that, then of the trainee. If you don’t believe that, then don’t take on trainees.don’t take on trainees.– (Trainees, try to find a mentor who cares about your success.)(Trainees, try to find a mentor who cares about your success.)

Explicit moral climate. We do science right! Explicit moral climate. We do science right! – Science needs ethical guidance from leadersScience needs ethical guidance from leaders

Enthusiasm for innovation and failures. What Enthusiasm for innovation and failures. What can we learn? rather than, you made a mistake! can we learn? rather than, you made a mistake! Openness. You can talk about your work.Openness. You can talk about your work.

Explicit guidelines for records, data Explicit guidelines for records, data management, authorshipmanagement, authorship

Irresponsible Conduct of ResearchIrresponsible Conduct of Research

Social responsibilitySocial responsibility

PerformancePerformance

ReportingReporting MentoringMentoring

CommunicationCommunication Conflicts of interestConflicts of interest

Proposing research to Proposing research to degrade othersdegrade others

Fabrication, Fabrication, falsificationfalsification

PlagiarismPlagiarism Exploiting, abusing Exploiting, abusing

traineestrainees SecrecySecrecy Failure to discloseFailure to disclose