Laboratory Ethics & Clinical Research Ethics Matthew George, Jr., Ph.D. Dr. Fred Lombardo

The Laboratory Notebook

Recording of Experimental Data Essential for protecting one’s intellectual property Essential for protecting one’s intellectual property Determining ownership of ideas Determining ownership of ideas Validation of results to support grants and manuscripts Validation of results to support grants and manuscripts Allow others to reproduce one’s work Allow others to reproduce one’s work

Components of the Notebook

Assigning the Lab Notebook

Notebook Instructions

Table of Contents

Numbered Pages

General Laboratory Rules* Each person in the lab should maintain a hardbound laboratory notebook with continuously numbered pages as a permanent record of his or her work and ideas Each person in the lab should maintain a hardbound laboratory notebook with continuously numbered pages as a permanent record of his or her work and ideas The notebooks should be kept in a safe place and not taken home The notebooks should be kept in a safe place and not taken home

General Lab Rules Continued Notebooks and their content are the property of the University laboratory Notebooks and their content are the property of the University laboratory The original notebook and all related data should be returned to the Laboratory Director when completed, upon request, or upon termination of employment The original notebook and all related data should be returned to the Laboratory Director when completed, upon request, or upon termination of employment * Source: Brad Thompson, Univ. of TX, Medical Branch, Galveston and the AMGDB (Association of Medical and Graduate Departments of Biochemistry) * Source: Brad Thompson, Univ. of TX, Medical Branch, Galveston and the AMGDB (Association of Medical and Graduate Departments of Biochemistry)

Additional Considerations The lab notebook and its content are considered to be confidential The lab notebook and its content are considered to be confidential Exercise great care in preserving them Exercise great care in preserving them Report the loss or theft of a research notebook to your group leader immediately Report the loss or theft of a research notebook to your group leader immediately

Each Notebook Should Include* Table of contents-listing each experiment (page numbers) and the location of all pertinent data Table of contents-listing each experiment (page numbers) and the location of all pertinent data Entries should be made in ink-not in pencil Entries should be made in ink-not in pencil Corrections should be made by making a single line-out (leaving the original legible) then adding the correction along with ones initials and the date Corrections should be made by making a single line-out (leaving the original legible) then adding the correction along with ones initials and the date

Notebook Inclusions (cont’d) Signature and date of who recorded the data Signature and date of who recorded the data Signature and date of a knowledgeable person who reviewed and understood the data Signature and date of a knowledgeable person who reviewed and understood the data *Source: Brad Thompson and AMGDB *Source: Brad Thompson and AMGDB

Each Experiment Should Include Title, experiment number and date Title, experiment number and date Names of persons involved in the experiment and how they participated Names of persons involved in the experiment and how they participated Statement of purpose (list the specific question(s) to be answered by the experiment Statement of purpose (list the specific question(s) to be answered by the experiment

Each Experiment Should Include (2) Experimental design. List key steps in the design. You may refer to previous experiments or recorded protocols used in your laboratory. If you deviate from what is in a prior protocol, record how it is different. Provide enough information so that a co-worker could continue from where you left off if you became ill. Experimental design. List key steps in the design. You may refer to previous experiments or recorded protocols used in your laboratory. If you deviate from what is in a prior protocol, record how it is different. Provide enough information so that a co-worker could continue from where you left off if you became ill.

Each Experiment Should Include (3) Results with original data. Include graphs or tables that summarize the data in your notebook Results with original data. Include graphs or tables that summarize the data in your notebook Conclusions. Meaning of results; problems; future plans Conclusions. Meaning of results; problems; future plans Remember, another person should be able to interpret and repeat what you have recorded Remember, another person should be able to interpret and repeat what you have recorded

Protection from Research Misconduct in the Laboratory- 1* Be sure you look carefully at raw data from your post-docs, students and technicians Be sure you look carefully at raw data from your post-docs, students and technicians Watch while your technicians, students, or post-docs do research in your lab Watch while your technicians, students, or post-docs do research in your lab Be sure you take concerns about data, or actual allegations, from your staff seriously Be sure you take concerns about data, or actual allegations, from your staff seriously

Protection from Research Misconduct in the Laboratory- 2* Be careful how you resolve disputes or break up with your former collaborators Be careful how you resolve disputes or break up with your former collaborators If you find evidence of misconduct in your lab, report it and remove yourself If you find evidence of misconduct in your lab, report it and remove yourself Don’t if you suspect misconduct, try a “trap” or “sting” without informing officials Don’t if you suspect misconduct, try a “trap” or “sting” without informing officials

Protection from Research Misconduct in the Laboratory- 3* Do good science, be a good mentor and show interest in your students’ work, and take responsibility for your laboratory’s research Do good science, be a good mentor and show interest in your students’ work, and take responsibility for your laboratory’s research *Source: Alan Price, Office of Research Integrity and the AMGDB *Source: Alan Price, Office of Research Integrity and the AMGDB

Other Types of Data Working with computer generated data Working with computer generated data Working with data generated from “kits” Working with data generated from “kits” Interview and/or evaluation data Interview and/or evaluation data Computer and photo-editing programs Computer and photo-editing programs

Basic Bioethics Two predominate philosophies governing ethics in the Western world: Two predominate philosophies governing ethics in the Western world: –Deontological view-I. Kant ( ) –Utilitarianism-John Locke ( ) and John Stuart Mill ( )

Deontology/Utilitarianism Deontology Deontology –The study of duties that persons have toward one another. –The categorical imperative of Immanuel Kant Utilitarianism Utilitarianism –The view that actions or policies are to be morally evaluated according to the extent to which they promote happiness or well-being

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

Elements of Informed Consent Threshold requirement: competence Threshold requirement: competence Information requirements Information requirements –Information –Understanding Consent requirements Consent requirements –Consent –Authorization

Informed Consent Benefits Benefits Risks Risks Alternatives Alternatives

Problems/Ethical Dilemmas Veracity- Truth Telling, is deception every justified? Veracity- Truth Telling, is deception every justified? Privacy/Confidentiality, is failure to protect the privacy of the patient every justified? Privacy/Confidentiality, is failure to protect the privacy of the patient every justified? Differences between obligations for privacy and for confidentiality Differences between obligations for privacy and for confidentiality

Dr.Woo Suk Hwang Dr. Hwang, veterinary scientist from Seoul National University cloned an Afghan hound named Snuppy (Seoul National University puppy). Named Director, Stem-Cell Center, Seoul, Korea. Branch labs planned for U.S. and U.K.

Dr. Hwang Aftermath Resigned as Director when it was reported that a member of his team had purchased human eggs from as many as 27 women for use in human stem cell experiments. Two female members of his team had donated eggs to the cause. Egg selling illegal in Korea Violation of scientific ethics for subordinates to provide ova, even if free of charge.

Bone Marrow Transplant Werner Bezwoda, University of Witwaterstrand, Johannesburg, South Africa Admitted that “he had committed a serius breach of scientific honesty and integrity” – –Petrs, WP, Dansey,RD et al,The Oncologist, 2000;5:1-13

Tuskegee Study ( ) Reasons given for continuing study Reasons given for continuing study –Long-term benefits for African-Americans –Contribution to scientific knowledge –Benefits for subjects (would receive other medical treatment) –Subjects were not harmed –Treatment might harm (Jarische-Herxheimer) –Should not waste data collected

Tuskegee Study ( ) Reasons given for not telling subjects the truth: Reasons given for not telling subjects the truth: –Subjects incapable of understanding –Scientists better equipped to determine what would benefit the subjects (paternalism) –Better to sacrifice a few for the greater good of the whole (utilitarianism)

Tuskegee Study ( ) Reasons for breach of veracity tenet continued: Reasons for breach of veracity tenet continued: –Subjects in the study were better off than those not selected to participate. –Long-term scientific goals were of greater importance than rights of an individual (Kant’s Categorical Imperative is breached)

Egregious Examples of Unethical Research Tuskegee Syphilis Study ( ) Tuskegee Syphilis Study ( ) Nazi Experiments on Prisoners-WW II Nazi Experiments on Prisoners-WW II Willow Brook Study-1960’s Willow Brook Study-1960’s Human Radiation Experiments Human Radiation Experiments LSD Experiments 1930s LSD Experiments 1930s Serratia marcescens experiments Serratia marcescens experiments Bacillus subtilis experiments Bacillus subtilis experiments

Belmont Report Principles: Principles: –Respect for persons’ consent, privacy, confidentiality –Beneficence (Benefits versus Risks) –Justice/Equality

45 Code of Federal Regulations Risks to subjects minimized Risks to subjects minimized Risks reasonable in relation to anticipated benefits. Risks reasonable in relation to anticipated benefits. Selection of subjects equitable Selection of subjects equitable Provision for safety monitoring Provision for safety monitoring Informed consent documented Informed consent documented

45 CFR Part There is adequate provisions to protect the privacy of subjects and to maintain confidentiality of data There is adequate provisions to protect the privacy of subjects and to maintain confidentiality of data Where any of the subjects are likely to be vulnerable to coercion (“susceptible to kindness”) or undue influence, additional safeguards are incorporated to protect the subjects. Where any of the subjects are likely to be vulnerable to coercion (“susceptible to kindness”) or undue influence, additional safeguards are incorporated to protect the subjects.

The Nuremberg Code The voluntary consent of the human subject is absolutely essential. The voluntary consent of the human subject is absolutely essential. The experiment should be such as to yield fruitful results for the good of society. The experiment should be such as to yield fruitful results for the good of society. Experiment based on results of animal experiments and knowledge of the natural history of the disease or problem Experiment based on results of animal experiments and knowledge of the natural history of the disease or problem

The Nuremberg Code The experiment should be conducted as to avoid all unnecessary physical and mental suffering and injury. The experiment should be conducted as to avoid all unnecessary physical and mental suffering and injury. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur;except in those experiments where the investigators serve as subjects. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur;except in those experiments where the investigators serve as subjects.

The Nuremberg Code The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.

The Nuremberg Code The experiment should be conducted only by scientifically qualified persons. The experiment should be conducted only by scientifically qualified persons. During the course of the experiment the human subject should be at liberty to bring the experiment to an end (Intention to Treat Precepts) During the course of the experiment the human subject should be at liberty to bring the experiment to an end (Intention to Treat Precepts)

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

Resources “Biochemistry Laboratory: Modern Theory and Techniques”. Rodney Boyer. Benjamin Cummings, New York, 2006 “Biochemistry Laboratory: Modern Theory and Techniques”. Rodney Boyer. Benjamin Cummings, New York, 2006 Alan Price, Ph.D “How to protect your faculty and department from research misconduct allegations”. AMGDB Chairs Meeting Alan Price, Ph.D “How to protect your faculty and department from research misconduct allegations”. AMGDB Chairs Meeting Brad Thompson, Ph.D “Guidelines for laboratory record keeping”. AMGDB Chairs Meeting Brad Thompson, Ph.D “Guidelines for laboratory record keeping”. AMGDB Chairs Meeting

References-Ethics Loewy EH.Textbook of healthcare ethics. New York:Plenum Press, Loewy EH.Textbook of healthcare ethics. New York:Plenum Press, Veatch RM. A theory of medical ethics. New York:Basic Books,Inc,Publishers, Veatch RM. A theory of medical ethics. New York:Basic Books,Inc,Publishers, Beauchamp TLC, Childress JF.Principles of biomedical ethics.6th ed. New York: Oxford University Press, Beauchamp TLC, Childress JF.Principles of biomedical ethics.6th ed. New York: Oxford University Press, 2009.

References-Ethics Code of Ethics for Pharmacists. Adopted by membership of American Pharmaceutical Association, Washington, DC. October 27, Code of Ethics for Pharmacists. Adopted by membership of American Pharmaceutical Association, Washington, DC. October 27, Veatch RM. Hospital Pharmacy:what is ethical ? (Primer) Am J Hosp Pharm 1989, 46(Jan): Veatch RM. Hospital Pharmacy:what is ethical ? (Primer) Am J Hosp Pharm 1989, 46(Jan): Veatch, RM, Haddad, A, Case Studies in Pharmacy Ethics, 2 nd Ed., Oxford University Press, Veatch, RM, Haddad, A, Case Studies in Pharmacy Ethics, 2 nd Ed., Oxford University Press, 2008.

References-Ethics Arnold RM, Nissen JC, Campbell NA. Ethical issues in a drug information center. Drug Intell Clin Pharm 1987; 21(Dec): Arnold RM, Nissen JC, Campbell NA. Ethical issues in a drug information center. Drug Intell Clin Pharm 1987; 21(Dec): Kelly WN, Krause EC, Krowsinski WJ, Small, TR, Drane JF. National survey of ethical issues presented to drug inf.centers. Amer J Hosp Pharm 1990;47(Oct) Kelly WN, Krause EC, Krowsinski WJ, Small, TR, Drane JF. National survey of ethical issues presented to drug inf.centers. Amer J Hosp Pharm 1990;47(Oct)