Transcript Justification of Animals Protocol Question #17

IACUC Training
for 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
ligand
Group IV needs 35 animals: 7 novel drugs X 5 animals per
drug
Total 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 a
Narrative 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 search
might 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.
16 November 2006