Responsible Conduct in Research: BRU Session

1. Responsible Conduct in Research: BRU Session Katrina A. Bramstedt, PhD (CCF Bioethics Dept.) Katy Kassimatis, MA (CCF Gen. Clinical Research Center)

2. Course Outline • 50-minute lecture (all students in one group) • Principles of research ethics • Study design, data collection, data storage • Record-keeping, data selection, digital data (e.g. gels) • Authorship • Misconduct & whistleblowing • Animal welfare • 60-minute small group case discussions • Data, Animal Welfare, Authorship

3. Course Objectives** • Recognize ethical obligations those conducting research • Identify elements of appropriate data management • Articulate the 3 requirements for authorship • Articulate 3 forms of research misconduct • Identify ethical principles associated with animal research **This is a general course to satisfy RCR education requirements.

4. Ethics is about… • Minimizing harm • Maximizing benefit • Being fair • Being respectful of others

5. People Often Ask Us… • If there is no law against a particular behavior then is the behavior ok? Can we be punished for a behavior that is not “illegal”? Our reply: • Do you need a law to tell you what is ethically inappropriate? • Lack of a legal statute does not give you permission to behave inappropriately.

6. Principles of Research Ethics • Honesty • Objectivity • Integrity (you, what you do, what you say) • Stewardship of resources (time, materials, equipment, personnel) • Collegiality (sharing) • Justice (fairness in authorship, mentoring) • Openness (disclosure)

7. Responsible Research Practice • What is it? • Following a written protocol • Thorough and legible data documentation (including reagent lot#, exp date, etc.) • Appropriately storing data and specimens • Appropriately storing reagents, chemicals • Proper equipment maintenance and calibration • Use of Standard Operating Procedures (SOPs) • Concern for welfare of research animals

8. Good Notekeeping • Signed and dated lab books • LEGIBLE writing • No white-out • Cross out with one line, initial and date. • No “sticky” notes • Have a blank page? Draw a line through it.

9. Types of Data • Body temperature • Body weight • Room temperature, humidity • Food/water use • Animal behavior (e.g., sleeping, aggression) • Assay data

10. Data Selection & Retention(aka Throwing out “bad” data) • Be careful how you “pick and chose” • Be consistent with regard to “high background”, “artifact”, “low confidence values”, and “noise” (versus signal) • When reporting your data, disclose what you did: • Two obese rats were excluded because… • The first three data points were excluded because…

11. Dilemmas with Gels & Digital Data(data enhancement) Gels, X-Rays, photos are considered DATA

12. Digital Data Ethics • Simple adjustments to the ENTIRE image are usually acceptable. • Selectively manipulating one area of the image is questionable. • Cropping an image is usually acceptable. • If used, software filters must be noted in the figure caption. • The more processing you ‘have’ to do, the more ethically problematic the manipulations become.

13. Who Owns “Your” Data & Materials? • Per CCF policy, any invention made by CCF employees & medical students that relate in any way to his/her job/research responsibilities must be assigned to the Clinic. • Exchanges of research material with outside researchers must be framed in written agreements, since further discoveries may be made using the material. CCF may be compensated for such exchanges.

14. Conflict of Interest • Financial • Equity interest, consultant, paid speaker • Non-financial • Recognition, desire to advance one’s theory • You might not be able to eliminate your conflicts of interest, but there are other options: reduce, avoid, disclose

15. http://www.dilbert.com/comics/dilbert/archive/dilbert-20051113.htmlhttp://www.dilbert.com/comics/dilbert/archive/dilbert-20051113.html

16. Authorship* Acquisition of funding, collection of data, or general supervision of the research group, alone, does not justify authorship. *Intl Comm of Medical Journal Editors. Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. November 2003.

17. An Underlying Principle of the Authorship Requirements • Those credited with authorship should be able to take public responsibility for the research.

18. Author Requirements* Authorship credit should be based on: 1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; and 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published. Authors should meet conditions 1, 2, and 3. *Intl Comm of Medical Journal Editors. Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. November 2003.

19. DON’TGIVE HONORARY AUTHORSHIP DON’TTAKE HONORARY AUTHORSHIP

20. Some Participating Journals • Annals of Clinical and Laboratory Science • Journal of Laboratory and Clinical Medicine • NEJM • Lancet • JAMA

21. A Word of Advice Decide up front who will work on the manuscript and what the order of authors will be. (Not all people working on the project will meet authorship requirements).

22. Research Misconduct • Fabrication (creating data) • Falsification (changing data) • Plagiarism (using another’s words or ideas without giving them credit). • This includes cutting and pasting from the Internet.

23. Why is Misconduct “Bad”? • It affects the integrity of science as a profession (which potentially adversely affects research funding) • It is not collegial • It is an example of poor resource stewardship • Propels further generation of “bad” data as the initial data foundation is “bad”

24. Misconduct Research • Survey of 3247 researchers: • 28% admitted to poor record keeping • 16% admitted to changing the design, methodology, or results of a study in response to pressure from their funding source • 15% admitted to dropping observations/data points based on a gut feeling • 10% admit to giving authorship to people who didn't earn it ref: Martinson et al.  Nature 2005;435:737-738

25. What to do if you suspect misconduct… • Don’t assume you are “right” • Don’t accuse • Try to verify your suspicion (there may be an acceptable reason for what is going on) • Ask yourself, “what is my motive for getting involved?” • Ask the advice of someone you trust

26. Issues in Animal Research Your Guides: PHS Policy on Humane Care and Use of Laboratory Animals – info about the role of the IACUC (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) Guide for the Care and Use of Laboratory Animals – info about vet care, housing, pain control euthanasia, etc. (http://www.nap.edu/readingroom/books/labrats/)

27. Issues in Animal Research • Have you attempted to REPLACE animals with another model? • Have you REDUCED the number of animals to the minimum needed for statistical purposes? • Have you REFINED your lab techniques so that animal pain and suffering are as low as possible? • Is your protocol approved by the CCF Institutional Animal Care and Use Committee?

28. Identification • Make sure your animals are clearly identifiable, whether singularly or in groups. • Options include cage labels, neck labels, tattoo, microchip, etc.

29. Housing Your Animals • Consider the animal species • Housing should consider size of animal, temperature, bedding needs, food, clean water, light, noise, humidity, contact with other animals, air exchange, vibration, etc. • Keep the cages clean, and the animals free from harm from other animals. (This includes avoiding crowding within a cage).

30. Avoiding Animal Stress If possible, before starting your project, CONDITION your animals to their environment, procedures, and research personnel.

31. Pain/Suffering • An animal with signs of pain or distress not predicted in the protocol, must have the pain or distress alleviated promptly. • Alleviation of such pain or distress must take precedence over completing a project. • If this is not possible the animal must be euthanized without delay.

32. Pain/Suffering • The use of local or general anesthetic, analgesic or tranquillizing agents must be appropriate to the species, and should at least parallel their use in current medical or veterinary practice. • If the nature of the project precludes the use of anesthetic or analgesic agents to alleviate pain, the planned end-point of the project must be as early as feasible to avoid or minimize pain or distress in the animals.

33. Pain/Suffering Neuromuscular blocking drugs do not provide relief from pain. They are used to paralyze skeletal muscles while an animal is fully anesthetized.

34. Post-Op Care • The comfort of animals must be promoted throughout the post-operative period, reflecting on warmth, hygiene, fluid and food intake, surgical wound healing, and control of infection, AND the use of analgesic, tranquillizers and antibiotics. • Ensure that animals recovering from anesthesia do not injure themselves by uncoordinated movements, and that conditions are such that they are not disturbed, attacked or killed by other animals in the same enclosure.

35. Killing of Research Animals • When it is necessary to kill a research animal, humane procedures must be used. These procedures must avoid pain or distress, be reliable and produce rapid loss of consciousness until death occurs. • Other animals should not be present when euthanasia is performed.

36. Red Face Test

37. Contact Information • Compliance Hotline: • (216) 791-4710 or (800) 826-9294. • Bioethics Consult Pager: • (216) 464-8410 x22512 • Office of General Counsel: • (216) 444-2340 * Please note all reports/complaints can be made anonymously to all groups listed.

38. Bibliography • Institute of Laboratory Animal Resources. Guide for the Care and Use of Laboratory Animals. 1996 • PHS Policy on Humane Care and Use of Laboratory Animals. 2002 • National Academy of Sciences. On Being a Scientist: Responsible Conduct in Research. Washington DC: Natl Academy Press, 1995. • University of Arizona Center for Toxicology. Digital Imaging: Ethics. http://swehsc.pharmacy.arizona.edu/exppath/micro/digimage_ethics.html 4. Intl Comm Medical Journal Editors. Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. November 2003. http://www.icmje.org/#author • Gunsalus CK. How to blow the whistle and still have a career afterwards. Sci Eng Ethics 1998;4:51-64. • CCF Innovation. Available on-line at http://intranet.ccf.org/ccfi/ • National Health and Medical Research Council Animal Welfare Committee. Australian code of practice for the care and use of animals for scientific purposes, 7th Edition. 2004, Canberra, Australia. • Macrina FL. Scientific Integrity. ASM Press, Washington DC, 2000.