16 November 2006 IACUC Training for Experienced Investigators What DO you want for Answers to Questions #14, #17 and the Narrative???

16 November 2006

IACUC Trainingfor Experienced Investigators

What DO you want for Answers to Questions #14, #17 and the Narrative???

16 November 2006

Protocol Question #14 How DO I Write a Meaningful

Lay Summary?

16 November 2006

Protocol Question #14 reads …

• In non-technical/lay terminology, what is the objective of the experiments proposed in this Animal Activity Protocol?

• Responses should be written in non-scientific language, as though explaining the study to a high school student.

• Responses should relate the proposed experiments to a human condition/disease.

• Why are the experiments important?

• What knowledge do you hope to achieve?

16 November 2006

Why include a Lay Summary ?!?!

One of the oft repeated questions from PIs to IACUC members is, "Why should we have to include in our research protocol a statement written in language that is immediately understood by the lay public about the relevance and purpose of the proposed research?"

Altogether apart from the fact that it is a government regulation, there are at least two reasons why this is important.

16 November 2006

Why include a Lay Summary ?!?!

Each IACUC is required to have at least one member from outside the field of medicine and research. That individual is often a professional in a completely different field. Like yourself, the lay member represents a certain interest which has its own vocabulary. The lay member's vocabulary might be just as perplexing and confusing to you, as your vocabulary is to the member. Also, remember that there is considerable diversity in the membership of IACUC which means that there are some members who work in different fields of research unrelated to the protocol under consideration.

16 November 2006

Why include a Lay Summary ?!?!

Whereas, it is true that the general public is not privy to the information included in research protocols, we live in a time when more and more individuals and organizations are being critical of research that uses animals. For the protection of the researcher and the institution an easily understood lay summary can help by giving the impression that nothing is being hidden from the public.

16 November 2006

"down to earth" practical suggestions From Our Lay Member – Mr. Clay Lee• Write your lay summary either at the very beginning or

the end of the creation of your protocol. For whatever reason the lay summary appears as item #14. I think you will agree it is difficult to suddenly change your vocabulary from technical to non technical and back to technical without endangering the outcome.

• Do not use technical language that only specialists in your field would understand.

• As you prepare your lay summary continuously ask yourself the question, "Would this be understandable to an eighth grader?"

16 November 2006

More "down to earth" practical suggestions

Always focus first and foremost on exactly what it is that you hope to accomplish through this particular research. More often than not you are working on something that would benefit all humans. The public is much more sympathetic if they feel that some common problem (e.g. diabetes, autism, drug addiction, cardiac disease, etc.) is the objective.

Remember that in the lay summary it is not necessary to tell how you are going to approach and complete your work; rather, what is the desired result.

16 November 2006

More "down to earth" practical suggestions

• It is good to note how you intend to build on previous research.

• Offer a brief and general overview of the intended use of the animals being requested in the protocol.

• Finally, simplicity is a virtue complemented by brevity.

16 November 2006

Protocol Question #17 How Do I Explain and Justify Number of Animals Requested for my Study?

16 November 2006

Protocol Question #17 reads……

• Explain and justify how the number of animals requested was determined. Flow diagrams/ tables to define animal use are encouraged. ***This number should support the request made in Protocol Item #9.***

16 November 2006

Federal Mandate For Animal

Number Justification

• Animal Welfare Act Regulations (AWAR) reads: “..approximate number of animals”

• PHS Policy states: “..minimum number required to obtain valid results”

• The Guide states: “..whenever possible, the number of animals requested should be justified statistically”

16 November 2006

Helping Hand From the IACUC

16 November 2006

When the IACUC evaluates the number of animals

requested for the proposed study, we … • look at Item #16 Experimental Design for number of

experimental groups, numbers of animals per experimental group; control groups; treatments within a group, etc

• Compare the number of animals noted in Item #17 with the experiments posed in question #16

• Compare the number of animals noted in Item #17 with number stated in Question #9

• All should be in agreement

16 November 2006

To explain how number of animals requested was determined, you can…

• Describe the request based on the number of animals used in your previous studies, if this is a 3 year full submission

• Discuss the request based on animal numbers used by other investigators doing similar work or from citations of published studies

16 November 2006

To justify how number of animals requested was determined , you can…

• Use Power Analysis and Statistics

OR

• Sample Size Justification based on citations of previous research in your lab or in labs using similar methodology and concept to make it reasonable to use similar sample size in proposed project

16 November 2006

If you use Power Analysis…

• You need to provide enough information to show the IACUC that you have selected the proper desired power (e.g. 80%) and level of significance (e.g., 0.05)

• If you need assistance contact• http://prevmed.umc.edu/biostat.html

16 November 2006

Division of Biostatistics - N408

• Edward F. Meydrech, Ph.D. • William D. Johnson, Ph.D. • Warren L. May, Ph.D. • Jake Olivier, Ph.D.

16 November 2006

Other Useful Websites…

• Experimental Design and Statistics in Biomedical Research (ILAR Journal)

• http://dels.nas.edu/ilar_n/ilarjournal/43_4/

• http://www.stat.uiowa.edu/%7Erlenth/Power/

16 November 2006

Example #1: Animals needed for a Teaching Protocol

Experimental Design question #16• Surgical techniques course consisting of 3 procedures

– AV anastomosis– Telemetry probe implantation– Cannulation of arteries and veins– See appendix C for details on surgical procedures

• For each session, male SD rats (250-350 grams) will be anesthetized

• Each session will have 8-10 students; Each student will require 2 rats (for each procedure) on which to practice and master the surgical techniques

• Sessions are offered once every six months • At conclusion of the procedures, animals will be sacrifice by

barbiturate overdose followed by bilateral pneumothorax

16 November 2006

Justification of Animals needed for the Teaching Protocol Described in #16

Animal Number Justification question #17

• 2 rat per procedure X 3 procedures [listed in #16] = 6 rats• Each class 8-10 students: maximum of 60 rats per class• Class offered twice per year: maximum of 120 rats per year• As this is a teaching lab, mastering techniques may lead to fatalities.

In our previous sessions, fatalities account for >5% of the total animals used. Therefore, we will need an additional 6 animals per year as replacements.

• Total of 378 rats for 3 years***• This number should agree with number in question #9

16 November 2006

Example #2: Animals in A Drug Study

Experimental Design question #16• Female cats are instrumented with ICV cannulae – see appendix C

for details of surgery• Wait week; begin drug testing• Divide cats into 5 groups with 5 cats in each group• Group I receives continuous drug [see appendix F] at 10 mg/kg

every day for 10 weeks [5 animals]• Group II receives drug + ligand every day for 10 weeks [5 animals]• Group III receives ligands at 5 ul/ml every day for 10 weeks**• Group IV received novel drugs 60 ug/kg every day for 10 weeks**• Group V receives saline every day for 10 weeks [5 animals]• Groups III and IV will receive 5 different ligands or 7 novel drugs• Animals will be sacrificed 12 weeks following the initial ICV surgery

16 November 2006

Justification of Animals Needed for Drug Studies described in #16

4 experimental groups [Groups I-IV] and 1 control group [Group V] each Group contains 5 animals per group

Groups I, II, V - need 15 animals Groups III needs 25 animals; 5 ligands X 5 animals per

ligandGroup IV needs 35 animals: 7 novel drugs X 5 animals per

drugTotal number of animals is 75 cats per year and 225 cats

for three years. Based on the literature [citation], as well as refinement of our experimental technique, we have reduced the number of animals needed to provide statistical significance by 15%.

16 November 2006

Example #3: Animals Needed for Physiological Recording Study

Experimental Design #16• Train monkey to sit and receive auditory and tactile

stimulation, receive juice reward: 3 months• Stereotaxic cephalic implant and stimulating electrodes

in the cerebellum [see appendix C for complete description of surgical procedure]: wait 1 week

• Daily, monkey placed into recording chamber; search for neurons that respond to specific auditory and/or tactile stimulation

• At end of recording time [9 to 17 months] monkey is sacrificed, brain removed for histology

16 November 2006

Determination and Justification of Animals Needed for This Study

• One monkey yields 12 neurons per electrode penetration into the target areas of the cerebellum

• Each area of interest is 6 mm2; 60 tracks can be placed in target area; yield a maximum of 720 neurons per target area

• There are 5 target areas of interest in the cerebellum; yield a maximum of 720 X 5 = 3600 neurons per animal

• Viable neurons of interest can be recorded from a monkey for 9 months to 17 months.

• We have identified 8 different types of neurons in our previous work; each animal yields a maximum of 400 neurons of each type. To reach statistical significance we need to identify 650 neurons of each type. To achieve this number of neurons requires two monkeys for the three years.

16 November 2006

How do I Conduct a Narrative and Alternative Search?

16 November 2006

Why does the IACUC require aNarrative and Alternative Search?

• Animal Care Policy #12…Provides guidance on the animal welfare regulations requirement to provide a written narrative of the consideration of alternatives to painful and distressful procedures.

• According to USDA APHIS, Animal Care Policy #12, "a comprehensive search is an effective and efficient method for demonstrating compliance with the requirement to consider alternatives to painful/distressful procedures.“

16 November 2006

Narrative and Alternative Search

• Describe the experiments• Develop a Search strategy should address

3 “Rs”: reduction, refinement and replacement

• Select appropriate search terms• Database selection: need to search more

than one• Run and evaluate the results• Document the findings

16 November 2006

Narrative should …

Address the 3 “R”s• Refinement = research procedures that

minimize pain and discomfort with proper analgesia

• Reduction = number of animals needed for statistical significance

• Replacement = with non-animal models, or lower sentinel animals, whenever possible

16 November 2006

Narrative should …

Consider Alternatives

• procedures that are less likely to cause pain and distress

• http://awic.nal.usda.gov/ - Animal Welfare Information Center – Alternatives

16 November 2006

Narrative and alternative searchmight include…

• Statements such as …• No satisfactory alternatives to painful procedures were

found using the above listed search terms• Based on the current literature, we have selected the

least painful or least stressful procedure(s) that is/are adequate to answer our question.

• While non-animal models are available to provide answers, they will be used in conjunction with animal experiments and , thus, can lead to a reduction in the number of animals needed for this project.

• Our study is not duplicative of other studies identified in by the search.

16 November 2006

USDA Animal Welfare Information Center Website

http://riley.nal.usda.gov/nal_display/index.php?info_center=3&tax_level=1&tax_subject=184

This site provides information on the

performance of a database search according to USDA.

Gives example searches

Provides a worksheet for literature searches

16 November 2006

SO, in this session…

• Review the importance of the Lay Summary

• Review Process for justification of animal numbers

• Review Method for Narrative and Alternative Search

• This information will be posted on the IACUC Website: http://iacuc.umc.edu/

16 November 2006

Several Additional FYI Items

1) Congress Approves Bill to Punish Threats Against Animal Researchers

2) A working group composed of 12 scientists and laboratory animal medicine veterinarians from Public Health Service Agencies reviewed a need for updating the standards of the current 1996 Guide. The group found no evidence to warrant revising the performance standards of the 1996 Guide.  These standards have allowed individual institutions the flexibility to adapt policies and procedures to their own institutional environments. 

3) Beginning in 2007, IACUC Sponsored Training Sessions will be MANDATORY for all individuals (PI, graduate students, Post-Doc, technicians) working with live animals.