Laboratory Ethics &Laboratory Ethics &Clinical Research EthicsClinical Research Ethics

Matthew George, Jr., Ph.D.Matthew George, Jr., Ph.D.

Dr. Fred LombardoDr. Fred Lombardo

The Laboratory NotebookThe Laboratory Notebook

Recording of Experimental Recording of Experimental DataData

• Essential for protecting one’s Essential for protecting one’s intellectual propertyintellectual property

• Determining ownership of ideasDetermining ownership of ideas

• Validation of results to support Validation of results to support grants and manuscriptsgrants and manuscripts

• Allow others to reproduce one’s workAllow others to reproduce one’s work

Components of the Components of the Notebook Notebook

Assigning the Lab NotebookAssigning the Lab Notebook

Notebook InstructionsNotebook Instructions

Table of ContentsTable of Contents

Numbered PagesNumbered Pages

General Laboratory Rules*General Laboratory Rules*

• Each person in the lab should Each person in the lab should maintain a hardbound laboratory maintain a hardbound laboratory notebook with continuously notebook with continuously numbered pages as a permanent numbered pages as a permanent record of his or her work and ideasrecord of his or her work and ideas

• The notebooks should be kept in a The notebooks should be kept in a safe place and not taken homesafe place and not taken home

General Lab Rules General Lab Rules ContinuedContinued• Notebooks and their content are the Notebooks and their content are the

property of the University laboratoryproperty of the University laboratory• The original notebook and all related The original notebook and all related

data should be returned to the data should be returned to the Laboratory Director when completed, Laboratory Director when completed, upon request, or upon termination of upon request, or upon termination of employmentemployment

• **Source: Brad Thompson, Univ. of TX, Medical Source: Brad Thompson, Univ. of TX, Medical Branch, Galveston and the AMGDB (Association of Branch, Galveston and the AMGDB (Association of Medical and Graduate Departments of Biochemistry)Medical and Graduate Departments of Biochemistry)

Additional ConsiderationsAdditional Considerations

• The lab notebook and its content are The lab notebook and its content are considered to be confidentialconsidered to be confidential

• Exercise great care in preserving Exercise great care in preserving themthem

• Report the loss or theft of a research Report the loss or theft of a research notebook to your group leader notebook to your group leader immediatelyimmediately

Each Notebook Should Each Notebook Should Include*Include*• Table of contents-listing each Table of contents-listing each

experiment (page numbers) and the experiment (page numbers) and the location of all pertinent datalocation of all pertinent data

• Entries should be made in ink-not in Entries should be made in ink-not in pencilpencil

• Corrections should be made by making Corrections should be made by making a single line-out (leaving the original a single line-out (leaving the original legible) then adding the correction legible) then adding the correction along with ones initials and the datealong with ones initials and the date

Notebook Inclusions (cont’d)Notebook Inclusions (cont’d)

• Signature and date of who recorded Signature and date of who recorded the datathe data

• Signature and date of a Signature and date of a knowledgeable person who reviewed knowledgeable person who reviewed and understood the dataand understood the data

• *Source: Brad Thompson and AMGDB*Source: Brad Thompson and AMGDB

Each Experiment Should Each Experiment Should IncludeInclude

• Title, experiment number and dateTitle, experiment number and date

• Names of persons involved in the Names of persons involved in the experiment and how they experiment and how they participatedparticipated

• Statement of purpose (list the Statement of purpose (list the specific question(s) to be answered specific question(s) to be answered by the experimentby the experiment

Each Experiment Should Each Experiment Should Include (2)Include (2)

• Experimental design. List key steps in Experimental design. List key steps in the design. You may refer to previous the design. You may refer to previous experiments or recorded protocols experiments or recorded protocols used in your laboratory. If you deviate used in your laboratory. If you deviate from what is in a prior protocol, record from what is in a prior protocol, record how it is different. Provide enough how it is different. Provide enough information so that a co-worker could information so that a co-worker could continue from where you left off if you continue from where you left off if you became ill.became ill.

Each Experiment Should Each Experiment Should Include (3)Include (3)

• Results with original data. Include Results with original data. Include graphs or tables that summarize the graphs or tables that summarize the data in your notebookdata in your notebook

• Conclusions. Meaning of results; Conclusions. Meaning of results; problems; future plansproblems; future plans

• Remember, another person should Remember, another person should be able to interpret and repeat what be able to interpret and repeat what you have recorded you have recorded

Protection from Research Protection from Research Misconduct in the Laboratory- Misconduct in the Laboratory- 1*1*• Be sure you look carefully at raw Be sure you look carefully at raw

data from your post-docs, students data from your post-docs, students and techniciansand technicians

• Watch while your technicians, Watch while your technicians, students, or post-docs do research in students, or post-docs do research in your labyour lab

• Be sure you take concerns about Be sure you take concerns about data, or actual allegations, from your data, or actual allegations, from your staff seriouslystaff seriously

Protection from Research Protection from Research Misconduct in the Laboratory- Misconduct in the Laboratory- 2*2*• Be careful how you resolve disputes or Be careful how you resolve disputes or

break up with your former collaboratorsbreak up with your former collaborators

• If you find evidence of misconduct in If you find evidence of misconduct in your lab, report it and remove yourselfyour lab, report it and remove yourself

• Don’t if you suspect misconduct, try a Don’t if you suspect misconduct, try a “trap” or “sting” without informing “trap” or “sting” without informing officialsofficials

Protection from Research Protection from Research Misconduct in the Laboratory- Misconduct in the Laboratory- 3*3*• Do good science, be a good mentor Do good science, be a good mentor

and show interest in your students’ and show interest in your students’ work, and take responsibility for your work, and take responsibility for your laboratory’s researchlaboratory’s research

• *Source: Alan Price, Office of *Source: Alan Price, Office of Research Integrity and the AMGDBResearch Integrity and the AMGDB

Other Types of DataOther Types of Data

• Working with computer generated Working with computer generated datadata

• Working with data generated from Working with data generated from “kits”“kits”

• Interview and/or evaluation dataInterview and/or evaluation data

• Computer and photo-editing Computer and photo-editing programs programs

Basic BioethicsBasic Bioethics

• Two predominate philosophies Two predominate philosophies governing ethics in the Western governing ethics in the Western world:world:– Deontological view-I. Kant (1724-1804)Deontological view-I. Kant (1724-1804)– Utilitarianism-John Locke (1632-1704) Utilitarianism-John Locke (1632-1704)

and John Stuart Mill (1806-1873)and John Stuart Mill (1806-1873)

Deontology/UtilitarianismDeontology/Utilitarianism

• DeontologyDeontology– The study of duties The study of duties

that persons have that persons have toward one toward one another.another.

– The categorical The categorical imperative of imperative of Immanuel KantImmanuel Kant

• UtilitarianismUtilitarianism– The view that The view that

actions or policies actions or policies are to be morally are to be morally evaluated evaluated according to the according to the extent to which extent to which they promote they promote happiness or well-happiness or well-beingbeing

Clinical BioethicsClinical Bioethics

• Principles:Principles:– Beneficence (To do Good)Beneficence (To do Good)– Nonmaleficence (Nonmaleficence (Primum non nocere)Primum non nocere)– Justice (Fairness)Justice (Fairness)– Autonomy (Self-determination)Autonomy (Self-determination)– Veracity (Truth telling)Veracity (Truth telling)– Utility (The greatest good for the Utility (The greatest good for the

greatest number)greatest number)

Elements of Informed Elements of Informed ConsentConsent

• Threshold requirement: competenceThreshold requirement: competence

• Information requirementsInformation requirements– InformationInformation– UnderstandingUnderstanding

• Consent requirementsConsent requirements– ConsentConsent– AuthorizationAuthorization

Informed ConsentInformed Consent

• BenefitsBenefits

• RisksRisks

• AlternativesAlternatives

Problems/Ethical DilemmasProblems/Ethical Dilemmas

• Veracity- Truth Telling, is deception Veracity- Truth Telling, is deception every justified?every justified?

• Privacy/Confidentiality, is failure to Privacy/Confidentiality, is failure to protect the privacy of the patient protect the privacy of the patient every justified?every justified?

• Differences between obligations for Differences between obligations for privacy and for confidentialityprivacy and for confidentiality

Tuskegee Study (1932-Tuskegee Study (1932-1972)1972)• Reasons given for continuing studyReasons given for continuing study

– Long-term benefits for African-AmericansLong-term benefits for African-Americans– Contribution to scientific knowledgeContribution to scientific knowledge– Benefits for subjects (would receive other Benefits for subjects (would receive other

medical treatment)medical treatment)– Subjects were not harmedSubjects were not harmed– Treatment might harm (Jarische-Treatment might harm (Jarische-

Herxheimer)Herxheimer)– Should not waste data collectedShould not waste data collected

Tuskegee Study (1932-Tuskegee Study (1932-1972)1972)

• Reasons given for not telling subjects Reasons given for not telling subjects the truth:the truth:– Subjects incapable of understandingSubjects incapable of understanding– Scientists better equipped to determine Scientists better equipped to determine

what would benefit the subjects what would benefit the subjects (paternalism)(paternalism)

– Better to sacrifice a few for the greater Better to sacrifice a few for the greater good of the whole (utilitarianism)good of the whole (utilitarianism)

Tuskegee Study (1932-Tuskegee Study (1932-1972)1972)

• Reasons for breach of veracity tenet Reasons for breach of veracity tenet continued:continued:– Subjects in the study were better off Subjects in the study were better off

than those not selected to participate.than those not selected to participate.– Long-term scientific goals were of Long-term scientific goals were of

greater importance than rights of an greater importance than rights of an individual (Kant’s Categorical Imperative individual (Kant’s Categorical Imperative is breached)is breached)

Egregious Examples of Egregious Examples of Unethical ResearchUnethical Research

• Tuskegee Syphilis Study (1932-1972)Tuskegee Syphilis Study (1932-1972)

• Nazi Experiments on Prisoners-WW IINazi Experiments on Prisoners-WW II

• Willow Brook Study-1960’sWillow Brook Study-1960’s

• Human Radiation Experiments 1950-Human Radiation Experiments 1950-19701970

• LSD Experiments 1930sLSD Experiments 1930s

• Serratia marcescensSerratia marcescens experiments experiments

• Bacillus subtilis Bacillus subtilis experimentsexperiments

Belmont ReportBelmont Report

• Principles:Principles:– Respect for persons’ consent, privacy, Respect for persons’ consent, privacy,

confidentialityconfidentiality– Beneficence (Benefits versus Risks)Beneficence (Benefits versus Risks)– Justice/EqualityJustice/Equality

45 Code of Federal 45 Code of Federal Regulations 46.111Regulations 46.111

• Risks to subjects minimizedRisks to subjects minimized

• Risks reasonable in relation to Risks reasonable in relation to anticipated benefits.anticipated benefits.

• Selection of subjects equitableSelection of subjects equitable

• Provision for safety monitoringProvision for safety monitoring

• Informed consent documentedInformed consent documented

45 CFR Part 46.11145 CFR Part 46.111

• There is adequate provisions to There is adequate provisions to protect the privacy of subjects and to protect the privacy of subjects and to maintain confidentiality of datamaintain confidentiality of data

• Where any of the subjects are likely Where any of the subjects are likely to be vulnerable to coercion to be vulnerable to coercion (“susceptible to kindness”) or undue (“susceptible to kindness”) or undue influence, additional safeguards are influence, additional safeguards are incorporated to protect the subjects.incorporated to protect the subjects.

The Nuremberg CodeThe Nuremberg Code

• The voluntary consent of the human The voluntary consent of the human subject is absolutely essential.subject is absolutely essential.

• The experiment should be such as to The experiment should be such as to yield fruitful results for the good of yield fruitful results for the good of society.society.

• Experiment based on results of animal Experiment based on results of animal experiments and knowledge of the experiments and knowledge of the natural history of the disease or problemnatural history of the disease or problem

The Nuremberg CodeThe Nuremberg Code

• The experiment should be conducted as The experiment should be conducted as to avoid all unnecessary physical and to avoid all unnecessary physical and mental suffering and injury.mental suffering and injury.

• No experiment should be conducted No experiment should be conducted where there is anwhere there is an a priori a priori reason to reason to believe that death or disabling injury will believe that death or disabling injury will occur;except in those experiments occur;except in those experiments where the investigators serve as where the investigators serve as subjects.subjects.

The Nuremberg CodeThe Nuremberg Code

• The degree of risk to be taken should The degree of risk to be taken should never exceed that determined by the never exceed that determined by the humanitarian importance of the problem humanitarian importance of the problem to be solved by the experiment.to be solved by the experiment.

• Proper preparations should be made and Proper preparations should be made and adequate facilities provided to protect adequate facilities provided to protect the experimental subject against even the experimental subject against even remote possibilities of injury, disability, or remote possibilities of injury, disability, or death.death.

The Nuremberg CodeThe Nuremberg Code

• The experiment should be conducted The experiment should be conducted only by scientifically qualified only by scientifically qualified persons.persons.

• During the course of the experiment During the course of the experiment the human subject should be at the human subject should be at liberty to bring the experiment to an liberty to bring the experiment to an end (Intention to Treat Precepts)end (Intention to Treat Precepts)

The Nuremberg CodeThe Nuremberg Code

• During the course of the experiment During the course of the experiment the scientist in charge must be the scientist in charge must be prepared to terminate the experiment prepared to terminate the experiment at any stage, if he/she has probable at any stage, if he/she has probable cause to believe, in the exercise of cause to believe, in the exercise of good faith, superior skill, and careful good faith, superior skill, and careful judgment that the continuation of the judgment that the continuation of the experiment is likely to cause injury, experiment is likely to cause injury, disability or death (Stopping Rules)disability or death (Stopping Rules)

ResourcesResources

• www.amgdb.org• ““Biochemistry Laboratory: Modern Theory Biochemistry Laboratory: Modern Theory

and Techniques”. Rodney Boyer. Benjamin and Techniques”. Rodney Boyer. Benjamin Cummings, New York, 2006Cummings, New York, 2006

• Alan Price, Ph.D. 2002. “How to protect Alan Price, Ph.D. 2002. “How to protect your faculty and department from your faculty and department from research misconduct allegations”. AMGDB research misconduct allegations”. AMGDB Chairs MeetingChairs Meeting

• Brad Thompson, Ph.D. 2003. “Guidelines Brad Thompson, Ph.D. 2003. “Guidelines for laboratory record keeping”. AMGDB for laboratory record keeping”. AMGDB Chairs Meeting Chairs Meeting

References-EthicsReferences-Ethics

• Loewy EH.Loewy EH.Textbook of healthcare Textbook of healthcare ethicsethics. New York:Plenum Press, 1996.. New York:Plenum Press, 1996.

• Veatch RM.Veatch RM. A theory of medical A theory of medical ethicsethics. New York:Basic . New York:Basic Books,Inc,Publishers, 1981.Books,Inc,Publishers, 1981.

• Beauchamp TLC, Childress Beauchamp TLC, Childress JF.JF.Principles of biomedical ethicsPrinciples of biomedical ethics.6th .6th ed. New York: Oxford University ed. New York: Oxford University Press, 2009.Press, 2009.

References-EthicsReferences-Ethics

• Code of Ethics for Pharmacists. Adopted by Code of Ethics for Pharmacists. Adopted by membership of American Pharmaceutical membership of American Pharmaceutical Association, Washington, DC. October 27, Association, Washington, DC. October 27, 1994.1994.

• Veatch RM. Hospital Pharmacy:what is Veatch RM. Hospital Pharmacy:what is ethical ? (Primer) ethical ? (Primer) Am J Hosp PharmAm J Hosp Pharm 1989, 1989, 46(Jan): 109-115.46(Jan): 109-115.

• Veatch, RM, Haddad, A, Case Studies in Veatch, RM, Haddad, A, Case Studies in Pharmacy Ethics, 2Pharmacy Ethics, 2ndnd Ed., Oxford University Ed., Oxford University Press, 2008.Press, 2008.

References-EthicsReferences-Ethics

• Arnold RM, Nissen JC, Campbell NA. Ethical Arnold RM, Nissen JC, Campbell NA. Ethical issues in a drug information center.issues in a drug information center. Drug Drug Intell Clin PharmIntell Clin Pharm 1987; 21(Dec):1008- 1987; 21(Dec):1008-1011.1011.

• Kelly WN, Krause EC, Krowsinski WJ, Small, Kelly WN, Krause EC, Krowsinski WJ, Small, TR, Drane JF. National survey of ethical TR, Drane JF. National survey of ethical issues presented to drug inf.centers. issues presented to drug inf.centers. Amer Amer J Hosp PharmJ Hosp Pharm 1990;47(Oct)2245-50. 1990;47(Oct)2245-50.