University of Pittsburgh s4

IACUC Modification Request Form Checklist

IMPORTANT: This form may only be used to modify protocols submitted and approved on the Word-based version of the protocol form. If your protocol was submitted and approved through Animal Research Online (ARO), you cannot use this form to modify your protocol. See the ARO User’s Guide for more information.

To expedite the review of your protocol, please make sure that you take the following steps before submitting your modification request:

 Completeness Make sure that the application is complete, including all yes/no questions, contingent questions and all required attachments. Also, make sure that your requested changes have been addressed in the proper category(s). For instance, test agent changes must be addressed in section 18. Incomplete or incorrect applications cannot be reviewed and will be returned for revision before review by the committee.

 Revised Protocol You must provide a revised protocol that incorporates the requested changes before your modification can be approved. While this is not required at the time of submission (except in the case of PI changes), it may help reviewers understand how the requested modifications fit in with the ongoing project, rendering certain questions unnecessary. If you need a copy of the most recently-approved protocol, please contact the IACUC office at 412-383-2008.

 Training Direct any personnel being added to make sure that all applicable training has been completed. See the IACUC Training Modules page for guidance on specific required training.

 Multiple Modifications The IACUC will only consider one modification request at a time for any given protocol. Modification requests submitted while a request is currently under review will be returned. If possible, try to address all of your anticipated changes in one request. While it may take a little longer to review, it will ultimately save you time and help the IACUC office to be as efficient as possible. UNIVERSITY OF PITTSBURGH INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE MODIFICATION REQUEST FORM 2010

This form is required to request changes to an approved IACUC protocol. Any changes requested cannot be implemented prior to IACUC review and approval.

Final approval will not be granted until the PI provides a revised protocol that incorporates all of the proposed changes. This revised version must be created using the most recently-approved version of the protocol. If you require a copy of this document, please contact the IACUC office.

This form must be submitted via email to [email protected]. No paper copies are accepted. You will receive notification of receipt via email within 5 business days.

Administrative modification requests will be approved by the IACUC office within 5-8 business days of receipt. Other modification requests will be sent to the Committee for review. Approximate time for approval is four weeks.

The IACUC can request at any time that a new protocol be submitted if they determine that too many modifications have been made to the original protocol application making it unclear.

The IACUC generally requires that in most cases requests above 25% will require a new protocol application. Requesting more than a 25% increase in animals can be submitted for review, but current policies require that such requests are automatically flagged for full committee review at the next full IACUC meeting.

The following items cannot be requested using this form. A new protocol application must be submitted to incorporate the following changes:

. Changing the species used . Adding procedures that do not logically relate to the specific aims of the original protocol . A proposed major change in the scientific aims of the original protocol application . Switching from non-survival to survival surgery . Switching from single to multiple major survival surgeries (major surgery opens a body cavity) When submitting a new protocol application for any of the changes above, please reference your current IACUC protocol number and explain the changes that you have added. This will assist the IACUC administrative staff in increasing the efficiency of your protocol review.

If you have any questions regarding this form, please contact the IACUC office at (412) 383-2008 or [email protected].

Protocol Information Principal Investigator: Protocol Number: Protocol Title: Phone Number: Email Address: Mailing Address:

II. Type(s) of Modification Requested

Check All That Complete Type Of Change Apply (X) section(s): ADDITION OR DELETION OF AN INVESTIGATOR OR CHANGE OF PI 1 PROTOCOL TITLE CHANGE OR ADDITIONAL PROTOCOL TITLE 2 CHANGE IN FUNDING SOURCE 3 Administrative CHANGE IN ANIMAL SOURCE OR VENDOR 4 Modifications ADDITION OF HOUSING OR EXPERIMENTATION AT ANOTHER INSTITUTION OR COMPANY 5 CHANGES IN ANIMAL STRAIN 6 HOUSING FACILITY CHANGE 7 NEW USE SITE / NEW OUTSIDE HOUSING SITE 8 ANESTHETIC/ANALGESIC CHANGES 9 CHANGE IN EUTHANASIA PLAN 10 CHANGES IN SURGICAL PROCEDURE(S) OR ADDITIONAL SURGICAL PROCEDURE(S) 11 REQUESTED CHANGES TO A NON-SURGICAL PROCEDURE(S) 12 Other REQUESTING AN INCREASE IN ANIMAL NUMBERS 13 Modifications CHANGING A PREVIOUSLY APPROVED USDA PAIN CATEGORY 14 SPECIAL HOUSING REQUESTS 15 CHANGE IN HUSBANDRY PROCEDURES 16 MODIFY OR ADD NEW TESTS OR AGENTS 17 OTHER CHANGES THAT LOGICALLY RELATE TO THE SPECIFIC AIMS OF THE ORIGINAL 18 PROTOCOL APPLICATION III. Modification Information (only complete sections which apply to the changes you are requesting)

1. ADDITION OR DELETION OF AN INVESTIGATOR ***Listed on Non- *PITT ID POSITION **PROJECT PHONE Add or E-MAIL Pitt NAME # TITLE DUTIES # Delete? IACUC Protocols?

Please state why these changes are requested. If this request involves a PI change, you MUST submit a revised protocol with #1-19, #36 and #87 readdressed for the new PI. If you require a copy of the most recently approved version of your protocol, please contact the IACUC office 412-383-2008.

* Do not list Social Security Numbers! **List the duties this person will perform relating to the animal studies. *** Indicate if the person is listed on an animal protocol from a University or Institution other than the University of Pittsburgh. If any of the personnel being added to this protocol are listed on animal protocols outside the University of Pittsburgh, please indicate the University or Institute for each person. The purpose of this question is to identify individuals who travel between different animal facilities and therefore may provide for potential cross- trafficking of infectious organisms.

2. PROTOCOL TITLE CHANGE OR ADDITIONAL PROTOCOL TITLE Previous Title: New Title to Replace Previous Title: Additional Title Requested: Please state why these changes are requested:

3. CHANGE IN FUNDING SOURCE Funding Source(s) to be removed: 4. New Funding Source(s) (If an outside grant(s), include title and number): Please state why these changes are requested:

If the new funding source does not conduct peer review (e.g., industry, departmental funds), has the letter of Scientific Merit been provided by the Dean, Dept Chair or Division Chief and attached to this application?

If you are adding a new source of funding, complete the conflict of interest declaration below. Does the principal investigator or any co-investigator or research coordinator involved in this study (or in aggregate with his/her spouse, dependents or other members of his/her household): Possess an equity interest in the entity that either sponsors this research or owns the technology being evaluated that exceeds 5% ownership interest or a current value of Yes No $10,000? Receive salary, royalty or other payments from the entity that either sponsors this research or owns the technology being evaluated that is expected to exceed $10,000 Yes No per year? Have rights to the intellectual property (IP) being evaluated – as either the inventor of the IP for which a patent has been issued, or as the inventor of the IP that has Yes No been optioned or licensed to a company? Have a financial relationship with a start-up company (which is being monitored by the Entrepreneurial Oversight Committee) that has an option or license to utilize the Yes No technology being evaluated? If yes to any item, please attach detailed information describing the nature of the relationship indicated above.

Please note that if the New Funding Source represents NIH Funds, you must also submit a just- in-time-review (http://www.iacuc.pitt.edu/forms/forms_iacuc.htm) so that the IACUC can ensure the animal research described in the New Funding Source is contained in the IACUC protocol. CHANGE IN ANIMAL SOURCE OR VENDOR Previous Animal Source or Vendor: New Animal Source of Vendor: Please state why these changes are requested:

5. ADDITION OF HOUSING OR EXPERIMENTATION AT ANOTHER INSTITUTION OR COMPANY If animals owned by the University will be housed or used at another insitution or company (for experimentation, rederivation, cryopreservation, custom animal production, etc.) please provide the company name, address, and name and phone number of a contact person at the company.

Please see the IACUC’s policy on Accepting Reviews from Other Institutions at http://www.iacuc.pitt.edu/sop/Accept_Approv.pdf.

6. CHANGES IN ANIMAL STRAIN Species Used: Previous Strain(s) Used: Proposed Strain(s): Please state why this change is necessary:

Will the requested strain(s), due to phenotypic changes or any other reason, require additional husbandry measures or caging (such as microisolator caging) that are not described on the approved protocol? (If Yes, this request does not qualify as an administrative modification request, as you must also complete section 15 and/or 16 below.)

Note: Rodents of an immunocompromised phenotype must be housed according to the Institutional Immunocompromised Rodent Husbandry policy, found at (http://www.iacuc.pitt.edu/sop/ImmunocompromisedRodents.pdf).

Please address how this change logically relates to the specific aims described in the approved protocol.

Will this change require additional animals? (If Yes, you must complete section 12).

7. HOUSING FACILITY CHANGE Currently Approved Housing Facility(s): (Housing Facility refers to University-managed animal facility locations, such as those managed by the DLAR) New Housing Facility(s):

Housing Facility(s) to Remove: Please state why these changes are requested:

If animals will be transported to the new location(s) for manipulations, then returned to the original facility, describe the route and mechanism of transport.

NOTE: Consultation with the site manager of the facility(s) being added is recommended before applying for IACUC approval.

8. NEW USAGE SITE / NEW OUTSIDE HOUSING SITE Currently Approved Use Site(s): (Use Site refers to a site that is outside DLAR facilities) New Use Site(s) to add:

Use Site(s) to delete:

Please explain why you cannot perform this work within DLAR space: Describe the transport route from the approved housing site to the new use site: Describe the containment and transport mechanism: IMPORTANT: If animals will be held in the new Use Site for greater than 12 hours for non terminal procedures, the new site is considered an outside housing site and requires the completion of the section below. New Outside Housing Site(s) to add (> 12 hrs):

Outside Housing Site(s) to delete:

Outside Housing Site(s) to remain:

*Please explain why you are requesting a new outside housing site: 9. ANESTHETIC/ANALGESIC CHANGES Proposed Anesthetic Dose (mg/kg) Route Frequency Duration

Please explain why you are adding/changing the anesthetic/analgesic:

Please indicate how you will monitor effectiveness of anesthetic/analgesic:

10. CHANGE IN EUTHANASIA PLAN Previous Method of Euthanasia: Proposed Method of Euthanasia: Dose: Route: Is this method accepted by the 2007 AVMA Panel on Euthanasia? (For more information, please visit: http://www.avma.org/issues/animal_welfare/euthanasia.pdf )

Please explain why this change is necessary:

11. CHANGES IN SURGICAL PROCEDURE(S) OR ADDITIONAL SURGICAL PROCEDURE(S) Please describe the change in surgical procedure or additional surgical procedure: Why is this change needed?

Please address how this change logically relates to the specific aims described in the approved protocol. Please describe any expected and/or potential complications. You answer must include the frequency of these complications and how you will address them. Will anesthetics/analgesics be given? If yes, section 9 must be completed Will this change the USDA pain classification? (If yes, section 14 must be completed.) Will this change require additional animals? (If yes, you must complete section 13.) Please note: If you add a procedure that has the potential to cause pain and/or distress in USDA regulated animals (any animal other than mouse, rat, bird or aquatics) then you must also include a revised literature search for Refinement, Reduction and Replacement (Appendix I below).

12. ADDITIONS OR CHANGE OF A NON-SURGICAL PROCEDURE Please describe the change or additional procedure:

Why is this change needed?

Please address how this change logically relates to the specific aims described in the approved protocol. Please describe any expected and/or potential complications. You answer must include the frequency of these complications and how you will address them. Will this procedure cause pain and/or distress to the animal? If yes, include how you will monitor and alleviate the pain and/or distress? Will this change the USDA pain classification? (If yes, section 14 must be completed.) Will this change require additional animals? (If yes, you must complete section 13.) Please note: If you add a procedure that has the potential to cause pain and/or distress in USDA regulated animals (any animal other than mouse, rat, bird or aquatics) then you must also include a revised literature search for Refinement, Reduction and Replacement (Appendix I below). If the research manipulation changes proposed in rodent subjects will alter the immune system in a manner that renders the animals immunocompromised or severely immunosuppressed they must be housed according to the Institutional Immunocompromised Rodent Husbandry policy (http://www.iacuc.pitt.edu/sop/ImmunocompromisedRodents.pdf). Please review question #15.

13. REQUESTING AN INCREASE IN ANIMAL NUMBERS Species Strain Number of Additional % Increase from Animals Requested original protocol

Please explain the need for additional animals and offer statistical justification when appropriate. The IACUC generally requires that increases above 25% require a new protocol application; however all requests will be reviewed.

Have previous modifications to this protocol been used to add animals? If Yes, how many animals were added previously: 14. CHANGING A PREVIOUSLY APPROVED USDA PAIN CATEGORY Please list the species, strain, and number of animals that will be categorized in a new USDA pain category:

Please list the new USDA category that will pertain to the animals listed above:

Please state why this change is necessary:

If the new USDA pain category is D or E, appendix 1 (below) must be completed if you are using a USDA regulated species.

15. SPECIAL HOUSING REQUESTS Please explain in detail your request for special housing considerations:

Why are these changes necessary?

16. CHANGE IN HUSBANDRY PROCEDURES Please describe in detail the animal husbandry procedural changes being requested:

Why are these changes necessary?

If deviations from such husbandry requirements are required, describe and scientifically justify alternative husbandry plans below.

If you are adding a breeding program to your protocol, you must also submit Attachment 5. Please contact the IACUC office at [email protected] to have a copy sent to you. Please note: Husbandry procedures dealing with rodents of an immunocompromised phenotype or manipulation that alters the immune system in a manner that renders the animal immunocompromised or severely immunosuppressed must be housed according to the Institutional Immunocompromised Rodent Husbandry Policy (http://www.iacuc.pitt.edu/sop/ImmunocompromisedRodents.pdf).

17. MODIFY OR ADD NEW TESTS OR AGENTS Please list the agent(s) that you wish to add to your protocol below: Biological Agents: (tissues or fluids, rDNA, tumor cells, non-replicating viruses) Radioisotopes or ionizing radiation:

Chemical Agents:

Antibiotics:

Enter the dose, route, frequency and duration details below: Dose (if applicable): Route: Frequency: Duration of Treatment: Why are these changes being requested?

Will this change require additional animals? (If Yes, you must complete section 13).

Describe any expected or potential complications that may arise as a result of these new tests or agents. You must also describe the frequency for each complication and indicated how you will address each complication should it arise.

18. OTHER CHANGES THAT LOGICALLY RELATE TO THE SPECIFIC AIMS OF THE ORIGINAL PROTOCOL APPLICATION Please list any other changes that need to be made to the IACUC application that are not addressed above and please explain why these changes are needed:

IV. APPLICANT’S CERTIFICATION:

The information provided in this form accurately represents the changes I propose for my previously approved IACUC application. I am aware that the Applicant’s Certifications, which I agreed to on the original application, will remain in effect.

Investigator Name: Date: Appendix 1 Consideration of Alternatives To Painful/Distressful Procedures This section is only applicable to warm-blooded species other than birds, mice of the genus Mus, and rats of the genus Rattus. If this protocol utilizes only rats, mice, birds or aquatics, please skip to section R.

This section applies to all USDA regulated species. A Reference Librarian is available for consultation in performing literature searches; to reach Melissa Ratajeski, MLIS, RLAT, call 648-1971 or email [email protected].

If any procedures fall into USDA's Classification D or E, causing more than momentary or slight pain or distress to the animals, USDA Policy 12 requires that you must address all three of the following issues: 1) You have refined potential pain-producing methods as much as possible to minimize distress. 2) You have reduced animal use as much as possible without jeopardizing statistical validity. 3) You have considered replacing potential pain-producing methods with other techniques (e.g., in vitro techniques, computer simulations, lower animal species, etc.).

As part of the response, you must provide written narratives that will convince the IACUC reviewers you have made a good faith effort to substantively address each of these three issues. You must also provide two sources of information to show that you have addressed each of the three issues. At least one of these sources of information should be a search of a scientific database. For each search executed, you must specify the database searched, the date of the search, time period covered by the database search, and the search strategy used. If you elect to search two databases to satisfy the consideration of alternatives, please note that OVID Medline, ClusterMed, and PubMed are search engines that all access the same database, Medline, produced by the National Library of Medicine, and thus employing a combination of these search engines is considered to be a single database search. Note: the investigator should retain all searches, as they are reviewable by federal agencies.

An alternate method of consideration for alternatives is consulting with an expert (e.g, DLAR veterinarian, another PI with extensive experience with the issue in question) or attending conferences or colloqui that provide relevant and up-to-date information directly related to the issue. When sources other than database searches are included, sufficient documentation, such as the consultant’s name and qualifications and the date and content of the consult, should be provided to the IACUC to demonstrate the expert’s knowledge on availability of alternatives in the specific field of study. For more information, see http://www.aphis.usda.gov/ac/ -Policy #12.

Instructions: For each section below, provide at least 2 database searches, or 1 database search + an expert consultation, then provide a written narrative. University of Pittsburgh Modification Form Version 1/07 Institutional Animal Care and Use Committee

1. Refinement Provide evidence that you have refined potential pain or distress-producing procedures as much as possible to minimize distress. Any procedure that may cause pain or distress to an animal must be addressed. Date of Search(s) Database(s) Searched Inclusive Date(s) of Search

Provide the search strategy (keywords and delimiters) used to search the literature. In addition, indicate the number of references obtained from the search. The following is an example of an abbreviated Replacement search.

Ovid MEDLINE(R) Daily Update, Ovid MEDLINE(R) # Searches Results 1 animal testing alternatives/ 1755 2 "animal use alternatives"/ 169 3 computer simulation/ 82535 4 disease models, animal/ 141555 5 1 or 2 or 3 or 4 225702 6 "Islets of Langerhans Transplantation"/ 6084 7 6 and 5 168 8 limit 7 to yr="1998 - 2009" 110

Provide Search Strategy and Results Below: Search Strategy / History Results

Source of Qualifications of Extent, Nature, and Content of Date of Expert Consultation Expert Expert Source Expert Consultation Information

Written narrative based exclusively on the information gathered from the literature search or expert consultation. Narratives must be clearly based on the information uncovered during the database searches or expert consultation, rather than anecdotal information. If a possible refinement was uncovered or is known, but will not be employed, discuss why.

2. Reduction - Provide evidence that you have reduced animal use as much as possible without jeopardizing statistical validity. Date of Search(s) Database(s) Searched Inclusive Date(s) of Search

25 University of Pittsburgh Modification Form Version 1/07 Institutional Animal Care and Use Committee

Provide Search Strategy Below: Search Strategy / History Results

Source of Qualifications of Extent, Nature, and Content of Expert Date of Expert Consultation Expert Source Expert Consultation Information

Written narrative based exclusively on the information gathered from the literature search or expert consultation. Narratives must be clearly based on the information uncovered during the database searches or expert consultation, rather than anecdotal information. If a possible reduction strategy was uncovered or is known, but will not be employed, please discuss why.

3. Replacement - Provide evidence that you have considered replacing potential pain or distress- producing methods with other techniques (e.g., in vitro techniques, computer simulations, etc.). Date of Search(s) Database(s) Searched Inclusive Date(s) of Search

Provide Search Strategy Below: Search Strategy / History Results

Source of Qualifications of Extent, Nature, and Content of Expert Date of Expert Consultation Expert Source Expert Consultation Information

Written narrative based exclusively on the information gathered from the literature search or expert consultation. Narratives must be clearly based on the information uncovered during the database searches or expert consultation, rather than anecdotal information. If a possible replacement model was uncovered or is known, but will not be employed, please discuss why.