GAO

United States General Accounting Office

Report to the Chairman and Ranking 

Minority Member, Committee on Armed 

Services, House of Representatives

July 1999 DOD ANIMAL 

RESEARCH

Controls on Animal 

Use Are Generally 

Effective, but 

Improvements Are 

Needed

GAO/NSIAD/HEHS-99-156

Page 1 GAO/NSIAD/HEHS-99-156 DOD Animal Research

United States General Accounting Office

Washington, D.C. 20548

National Security and

International Affairs Division

B-278778.1 Letter

July 8, 1999

The Honorable Floyd Spence

Chairman

The Honorable Ike Skelton

Ranking Minority Member

Committee on Armed Services

House of Representatives

In 1992 and 1994 the House Committee on Armed Services held hearings on 

concerns that had been raised by the public and animal welfare interest 

groups about Department of Defense (DOD) research projects that utilize 

animals and inadequate public disclosure of DOD’s activities involving the 

use of animals. DOD’s Inspector General also investigated DOD’s animal 

use projects and made several recommendations to improve oversight and 

public accountability. In response to the recommendations, DOD made 

several changes, including a new and publicly available database of animal 

use projects,1

 new practices for preparing and reviewing research, and an 

annual animal use report to Congress.

However, the public and animal welfare groups have continued to raise 

questions about whether DOD uses animals, particularly higher-order 

animals such as nonhuman primates, cats, dogs, and farm animals, 

appropriately. In light of these concerns, your Committee directed us to 

examine DOD’s management and oversight of its animal research 

programs.2

 As agreed with your offices, we examined to what extent 

projects funded or performed by DOD utilizing animals (1) were directed 

toward military objectives; (2) unnecessarily duplicated other research; 

and (3) incorporated alternatives that reduced, replaced, or refined the use 

of animals.

We reviewed relevant legislation, regulations, policies, and procedures and 

interviewed DOD and other federal officials as well as representatives from 

animal research and animal welfare interest groups. We also reviewed 

1

 In an earlier report we discussed strengths and limitations of the database. See DOD Animal 

Research: Improvements Needed in Quality of Biomedical Research Database

(GAO/NSIAD/HEHS-99-24, Dec. 14, 1998). 

2

 House Report 103-499 by the House Armed Services Committee in consideration of the National 

Defense Authorization Act for Fiscal Year 1995.

Letr
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DOD’s database of fiscal year 1996 animal use projects, the most current 

and complete information available at the time of our review, and collected 

information from various DOD program offices to determine the objectives 

of each of the projects. We chose 24 of these projects, concentrating on the 

areas of biological defense, combat casualty care, and radiation research, 

to examine the issues of unnecessary duplication and the consideration of 

alternatives.3

 We visited the 14 DOD and other research facilities where 

these projects were conducted to review applicable processes and records. 

We also contracted with independent experts to assist our evaluation of 

these projects. Our findings on the 24 projects are not generalizable to all 

DOD research that used animals in fiscal year 1996. See appendix I for a 

detailed discussion of our scope and methodology.

Results in Brief DOD’s controls over animal use were generally effective, but some 

improvements are needed to further ensure that animals are used 

appropriately. We were able to link all but one of the 805 animal use 

projects in fiscal year 1996 to a military objective or a congressionally 

directed program. About half the projects were directed toward military 

research objectives that evolved from formal DOD planning processes, 

while about 35 percent supported DOD missions such as medical training 

and education. Another 15 percent did not address a direct military need 

but were part of congressionally directed programs such as breast cancer 

research. Many of the projects that addressed military objectives also had 

civilian applications such as emergency medicine.

We did not identify any unnecessary duplication in the 24 research projects 

we reviewed. DOD employed measures to avoid or minimize unnecessary 

duplication. These measures included requiring investigators to conduct 

and document literature searches and submit project proposals for 

scientific and animal use reviews. Although the inherent limitations of any 

literature search constrain DOD’s ability to identify and avoid unnecessary 

duplication, DOD needs to clarify its requirement that investigators search 

particular databases of ongoing research to ensure that searches are 

consistently implemented. 

3

 Our study does not address several other areas where the public and animal welfare groups have 

raised concerns about DOD’s use of animals such as whether the results of animal tests can be 

extrapolated to humans and whether research on brain injuries should continue to be conducted with 

animals. 

Letr
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Although DOD considered and incorporated alternatives to replace and 

reduce the use of animals in the 24 research projects we reviewed, 

investigators could have used additional alternatives to refine experimental 

procedures in 8 of them. These refinements could have improved the 

welfare of the animals without compromising the projects’ objectives. For 

example, routine pain relief could have been administered in five studies of 

burn treatments. In two other studies, animals could have been euthanized 

earlier than the investigators proposed without affecting research results. 

However, we were unable to determine the extent to which refinement 

alternatives were considered in the development and review of these 

protocols because records did not document the alternatives that were 

considered and not adopted.

We are making recommendations to the Secretary of Defense intended to 

reduce the likelihood that proposed research unnecessarily duplicates 

other research and to improve the consideration of refinement alternatives.

Background In fiscal year 1996, DOD sponsored 805 projects using a total of 319,000 

animals.4 These projects were conducted at various DOD research and 

training facilities (such as the U.S. Army Medical Research Institute for 

Infectious Diseases) as well as at public and private research facilities 

(such as universities and hospitals) funded by DOD. The animals used 

ranged from fish and amphibians to farm animals and nonhuman primates. 

However, mice and rats accounted for 80 percent of the animals used.5

 

These projects encompassed a very diverse set of research, training, and 

education activities. For example, in several projects, DOD tested different 

vaccines and treatments on various species of monkeys that were exposed 

to biological warfare agents or infectious diseases. Other projects used 

sheep, pigs, rats, and rabbits to investigate burn treatment therapies. Some 

projects used rhesus monkeys, dogs, guinea pigs, ferrets, and rodents to 

assess the health effects of ionizing radiation. Furthermore, as part of their 

training in emergency medicine, military surgeons and medics performed 

practice surgeries on pigs, goats, and other animals.

4

 DOD was unable to provide us with an estimate of the total cost of these projects but did provide an 

estimate for its animal use projects for fiscal year 1997, amounting to about $100 million. 

5

 DOD summarized the data in Department of Defense Animal Care and Use Programs 1996: Report to 

the Senate Armed Services Committee and the House of Representatives National Security Committee.
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DOD is subject to federal laws and regulations governing how animals are 

used as subjects in research and training projects. These laws and 

regulations establish standards for the care and use of animals in research 

and training, including requirements to minimize the potential for 

unnecessary duplication and promote the use of alternatives.6

 In addition, 

DOD has established its own policies and guidelines governing animal use. 

DOD officials and other experts generally agree that unnecessary 

duplication, although not formally defined by law or regulation, refers to 

research that repeats existing procedures without contributing to the 

advancement of scientific knowledge or presenting new information. 

Some duplication is usually necessary because research results must be 

reproducible. Reproduction is achieved when investigators replicate prior 

research to determine whether similar results do occur. DOD and other 

experts view alternatives as methods (such as computer simulation and 

cell culture techniques) that replace or reduce the number of laboratory 

animals required for an investigation or refine an existing procedure to 

minimize an animal’s pain or distress.

Overall responsibility for establishing policies on animal use activities 

within DOD resides with the Director of Defense Research and 

Engineering, while implementation of the policies resides with each armed 

service or Defense agency such as the Armed Forces Radiobiology 

Research Institute. The principal agent for ensuring that regulations and 

policies are implemented at DOD and non-DOD facilities rests with 

institutional animal care and use committees (IACUC). DOD’s policy is 

that its IACUCs have a minimum of five members, including at least one 

doctor of veterinary medicine and at least one member not affiliated with 

the institution in any other way. 

DOD’s process to reduce unnecessary duplication and promote alternatives 

relies upon investigators to prepare detailed plans—called protocols—of 

their proposed animal use activities and several levels of review of these 

protocols. DOD’s policy states that protocols must contain descriptions of 

the research or training activity, justifications for the use of the animals, 

descriptions of the experimental procedures, steps to be taken to protect 

the welfare of the animals, and the results of literature searches carried out 

to detect unnecessary duplication and availability of alternatives. These 

items are included in DOD’s standard protocol format, which was adopted 

6

 The Animal Welfare Act, 7 U.S.C. 2131-2158, as amended which is implemented by USDA regulations 9 

C.F.R. Parts 1-4; and the Health Research Extension Act of 1985, 42 U.S.C. 289d.
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for fiscal year 1996. Before investigators can begin using animals, the DOD 

funding agency reviews their protocols for scientific merit, and the IACUC 

reviews them for animal care considerations. As part of their review, 

IACUCs assess whether available alternatives were considered and 

adopted where appropriate. In addition, DOD requires that a service-level 

veterinarian review all its projects at non-DOD facilities as well as projects 

at DOD facilities using nonhuman primates. See appendix II for a detailed 

discussion of DOD’s process for reviewing animal use projects.

DOD Animal Use 

Projects Generally 

Addressed Military 

Objectives or 

Congressional 

Directives

We were able to link all but one of the 805 animal use projects in fiscal year 

1996 to military objectives or congressionally directed programs. Projects 

addressing military objectives included a variety of research, training, and 

education activities, while those addressing congressionally directed 

programs were primarily outside DOD’s military mission in areas such as 

breast cancer research. Many of the animal use projects directed at 

military objectives also addressed civilian needs. 

We attempted to collect information on the objectives of DOD’s animal use 

projects from its fiscal year 1996 Biomedical Research Database (BRD), a 

central source of information on the 805 projects conducted that year. 

While it contained information on the location of the research and a brief 

statement of the projects’ research objectives and methods, the database 

lacked information on the link between the projects and specific military or 

congressional objectives.7

 As a result, we had to contact 16 different DOD 

program offices, including the U.S. Army Medical Research and Materiel 

Command, the Office of Naval Research, the Air Force Office of Scientific 

Research, and the Armed Forces Radiobiology Research Institute (AFRRI), 

to obtain information on objectives. 

The individual program offices varied in how they were able to identify 

objectives for the projects. Officials in some offices were able to do so 

using documentation in existing records. In other offices, however, DOD 

lacked documentation, but program officials used their knowledge of the 

work to link each project. We were able to link 688 of the 805 projects to 

military objectives and another 116 to congressionally directed programs 

that did not have direct military relevance (see table 1).

7

 In December 1998 we recommended that DOD more clearly link projects with research goals and 

justifications in the BRD. See DOD Animal Research (GAO/NSIAD/HEHS-99-24, Dec. 14, 1998).
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Table 1: DOD Animal Use Objectives (fiscal year 1996) 

Of the 688 projects that we found linked to military objectives, 388 

addressed specific military research objectives identified through DOD’s 

formal research planning processes. These 388 projects used most of the 

animals as well as most of the nonhuman primates.

The projects’ objectives evolved from processes that DOD and each of the 

services established to identify operational military requirements and 

develop appropriate research to address these requirements. Each year, 

DOD’s Director of Defense Research and Engineering develops formal 

Objectives

Number of

projects

Objectives developed within a formal research planning process to 

support military objectives

Combat casualty care 87

Infectious diseases 70

Biological weapons defense 67

Operational medicine 57

Toxicity studies and environmental assessments 43

Medical chemical defense 30

Sensor development 16

Assessing effects of naval activities on marine mammals 14

Medical radiological defense 4

Subtotal 388

Objectives that supported other military needs

Clinical investigations 146

Training 82

Toxicity evaluations 31

Other mission objectives 41

Subtotal 300

Objectives that supported congressionally directed programs

Breast cancer research 98

Pathology research 17

Neurotransmitter research 1

Subtotal 116

Objectives not linked to military needs or congressionally directed 

programs 1

Total 805
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programming guidance for each of the services to help ensure that their 

research efforts support the current and long-term needs of the 

Department. This guidance is provided primarily in three plans: the Basic 

Research Plan, the Defense Technology Area Plan, and the Joint 

Warfighting Science and Technology Plan, which identify objectives and 

investment strategies for technologies critical to DOD’s missions. Each 

service has its own planning and review process to address the objectives 

identified in the plans and to develop other objectives and strategies to 

meet its own research needs. The services collect input from other DOD 

components that are the principal users of the research results and match 

their own needs with existing budget resources and research capabilities. 

The services then develop and publish specific annual research plans. 

Various programs conduct individual research projects to support these 

specified research objectives. 

The projects that were linked to research objectives developed within 

DOD’s formal research planning process were designed to improve the 

readiness and capabilities of servicemembers by developing information, 

products, and technologies. For example, the infectious disease projects 

used nonhuman primates and other animals to develop vaccines to protect 

servicemembers from infectious diseases such as malaria, dengue fever, 

hepatitis, and typhus. The operational medicine objective included 

projects using rats and other animals to develop countermeasures against 

the effects of operational stress (such as sleep deprivation and fatigue) on 

military performance. The sensor development projects used marine 

mammals and other animals to develop information to improve the 

military’s ability to detect underwater and airborne objects. 

The projects that supported other military objectives did not focus on 

meeting DOD’s operational research requirements. Instead, they supported 

other mission-related activities such as medical education and training. 

For example, faculty, students, and physicians at DOD medical treatment 

and training centers conducted clinical investigations to improve the 

knowledge and skills of medical professionals. One clinical investigation 

project used hamsters to determine the effect of high-pressure oxygen on 

tumors of the mouth. The training projects were intended to develop the 

skills of medics, corpsmen, and other military medical personnel. For 

example, cats and ferrets were used in several military hospitals in the 

training of physicians in inserting tracheal tubes into pediatric patients. 

The toxicity testing projects used different animals to evaluate the health 

hazards of various munitions and compounds found on military bases.
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The projects conducted as part of congressionally directed research 

programs did not address direct military objectives. Most of them were part 

of the congressionally directed Breast Cancer Research Program, 

administered by the Army. These projects investigated a wide range of 

concerns about breast cancer, including molecular biology, detection, 

diagnosis, and treatment. The pathology projects were conducted at the 

Armed Forces Institute of Pathology as part of a congressionally directed 

research program in which DOD pathologists collaborate with civilian 

pathologists. 

We were unable to link one project with a military need or a 

congressionally directed program. In this project, a private corporation 

conducted anemia research on rabbits in a Navy laboratory overseas. DOD 

officials agreed with our assessment that this project, which has ended, did 

not address a military need or a congressionally directed program. 

We found that some of the projects that addressed military objectives also 

had civilian applications because the medical needs of military personnel 

are often similar to those of the civilian population. In particular, projects 

addressing combat casualty care and infectious diseases for military 

personnel have direct relevance to the treatment and care of civilians. For 

example, as part of its combat casualty care program, the Army used pigs 

and rabbits to develop and test a fibrin bandage containing plasma proteins 

that accelerate blood clotting. The Army is currently collaborating with the 

American Red Cross to commercialize this technology for uses in both the 

military and civilian sectors. Similarly, DOD used nonhuman primates and 

other animals to develop vaccines against hepatitis, malaria, dengue virus, 

and other infectious diseases that affect military and civilian populations.

DOD Efforts to Avoid 

Unnecessary 

Duplication Generally 

Succeeded

We did not identify any cases of unnecessary duplication in our review of 

24 DOD-funded research projects that used animals in fiscal year 1996. 

DOD, research facilities, and investigators employed several measures to 

minimize the risk of duplicating other studies unnecessarily. Nonetheless, 

certain factors such as the limited effectiveness of literature searches could 

affect DOD’s ability to systematically identify and avoid unnecessary 

duplication. 
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No Evidence of 

Unnecessary Duplication in 

24 Projects

We identified no unnecessary duplication in the 24 research projects 

conducted in fiscal year 1996 that we reviewed. We evaluated each project 

in several ways. We reviewed the materials used in the original 

consideration and approval of the project and interviewed principal 

investigators and IACUC members to determine how they addressed the 

likelihood that the project would unnecessarily duplicate other studies. We 

provided the same materials to the U.S. Department of Agriculture’s Animal 

Welfare Information Center (AWIC) and had its information specialists 

conduct an independent search of scientific literature relevant to each 

project.8

 We then had a nationally recognized subject matter expert and 

two experts in research methodology and animal use alternatives 

separately review the materials and the AWIC literature search for each 

project.

Practices Used to Help 

Avoid Unnecessary 

Duplication 

Each of the 14 facilities we visited had practices in place to help ensure that 

investigators’ research did not unnecessarily duplicate other studies. 

Investigators conducted searches of published literature in their fields. 

The literature searches varied in the number and types of databases used. 

However, as recommended by DOD, investigators generally searched major 

databases such as MEDLINE.9

 Investigators of the 24 research protocols 

provided written assurance, as required, that they had made a good faith 

effort to ensure that their project would not unnecessarily duplicate other 

research. 

Investigators we spoke with also mentioned other practices they employed 

to reduce the likelihood of unnecessary duplication. They emphasized that 

attending seminars and conferences in their particular subject area, 

consulting and collaborating with other experts, and reviewing relevant 

professional publications all contributed to their ability to stay current in 

their field. Investigators further noted that the desire to publish results of 

their findings in peer-reviewed journals provided additional incentive for 

avoiding unnecessary duplication because journals seek to publish 

research that could advance science. All but four of the projects we 

8

 AWIC, an information service of the National Agricultural Library, was established to provide technical 

assistance in conducting searches to identify alternatives. 

9

 MEDLINE is the National Library of Medicine’s bibliographic database covering the fields of medicine, 

nursing, dentistry, veterinary medicine, health care systems, and other sciences. The MEDLINE file 

contains bibliographic citations and author abstracts from approximately 3,900 biomedical journals 

published in the United States and 70 other countries.
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reviewed resulted in one or more peer-reviewed publications and/or 

conference presentations.

The 24 research projects also went through several reviews that partly 

addressed the potential for unnecessary duplication. For example, all but 

one project went through a scientific merit review. According to DOD 

guidance, such reviews include a consideration of the project’s 

contribution to science. Scientists and department heads located at DOD’s 

research facilities conducted scientific merit reviews for 16 of the 17 

sampled projects at those facilities. As for the remaining project, an agency 

official told us that a science review was not required at the time the 

project was approved. The seven projects at the non-DOD facilities we 

visited went through either a peer review by non-DOD scientists or a 

review by a DOD scientist from the program funding office.

Each project was also reviewed by the IACUC at its research facility. Some 

of the IACUC chairpersons stated they reviewed the investigators’ written 

assurance statements and literature search documentation. The IACUCs 

relied on investigators to review abstracts and articles obtained from 

literature searches, and identify unnecessarily duplicative research. 

However, the IACUCs generally did not independently replicate the 

literature searches. Some of the IACUCs used other resources to assist 

them in their review. For example, the IACUC at one DOD facility required 

investigators to work with a reference librarian to perform literature 

searches and submit the search results for IACUC review. At two DOD and 

one non-DOD facility, a reference librarian served as an IACUC member to 

focus on the quality and appropriateness of the investigators’ literature 

searches. 

DOD also requires that a service-level veterinarian trained or experienced 

in laboratory animal science and medicine perform a review of all projects 

at non-DOD facilities as well as projects involving the use of nonhuman 

primates. The purpose of these reviews is to ensure that the research 

projects adhere to DOD’s policies and requirements. DOD, however, did 

not always enforce its requirement for these service-level veterinarian 

reviews. We found that one Defense Advanced Research Projects Agency 

(DARPA) and two AFRRI projects did not receive the required service-level 

veterinary reviews because no veterinarian was assigned to them. For the 

DARPA project, a service-level veterinarian was not assigned to review the 

protocol until approximately 1 year after the project began. The two 

AFRRI projects were completed without ever receiving such a review. 

When we pointed out this problem to AFRRI officials, they made 
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arrangements to have a service-level veterinarian perform the required 

reviews on all their ongoing projects that use nonhuman primates.

Two Factors Could Limit the 

Effectiveness of Literature 

Searches

Although DOD relies on literature searches as a key element to reduce the 

likelihood that proposed research would duplicate other work 

unnecessarily, two factors could limit the searches’ effectiveness. First, the 

services and Defense agencies that sponsor research at non-DOD facilities 

differed in their implementation of a key aspect of literature search 

requirements. Second, literature searches are limited in their ability to 

identify potentially duplicative research because not all research is 

published. 

Since 1995, DOD has required that all investigators search the Defense 

Technical Information Center (DTIC) and the Federal Research in Progress 

(FEDRIP) databases or their equivalents. Searching these databases is 

important because they are the primary sources of information on research 

in progress in the federal government. We previously reported that it is 

important that investigators have access to such information because of 

the time lag between completing research and publishing.10

We found, however, that the policy on searching these databases of ongoing 

research or their equivalents is not clear. In particular, service-level 

veterinarians differed in their interpretation of the meaning of equivalent. 

For example, the veterinarian who reviewed DARPA projects told us that 

he does not recognize any other databases in lieu of DTIC and FEDR IP. 

However, the Army’s veterinarian considers MEDLINE to be the equivalent 

of FEDRIP. In contrast, the Navy’s veterinarian told us that he does not 

accept MEDLINE as an equivalent to FEDRIP but does accept a search of 

the National Technical Information Service database.11

Although DOD officials, principal investigators, and experts emphasized 

the importance of conducting literature searches, they also noted that 

literature searches have inherent limitations in identifying unnecessary 

duplication. These limitations affect all research, whether funded by DOD 

10 Biological Warfare: Better Controls in DOD’s Research Could Prevent Unneeded Expenditures

(GAO/NSIAD-91-68, Dec. 27, 1990).

11 The National Technical Information Service is the government’s central source for the sale of 

scientific, technical, engineering, and related business information produced by or for the U.S. 

government.
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or by other public or private organizations. For example, studies that show 

no effect are not generally published. In addition, some research involves 

proprietary information and rarely gets published; other research involves 

classified information and never gets published. Because of all the 

research that is not published, investigators may not be able to identify the 

full extent of research that has been conducted in their field.

DOD Could Do More to 

Promote the Use of 

Alternatives 

Although DOD’s efforts to promote alternatives in animal research have 

generally been successful in the replacement or reduction of the animals 

used, we found additional refinements that could have been implemented 

to reduce animals’ pain or distress in 8 of the 24 protocols. We found two 

additional projects in which investigators and IACUCs could have more 

closely addressed alternatives after investigators proposed changes to 

previously approved protocols. Identifying and implementing alternatives 

is challenging, but investigators did not adequately document the 

alternatives that were considered when they designed their studies. 

Protocols Addressed 

Replacement and Reduction 

Alternatives

In the 24 protocols we reviewed, investigators addressed replacement and 

reduction issues as required by explaining why they planned to use animals 

and the proposed species and numbers of animals. To assess DOD’s use of 

alternatives, we reviewed materials used in the original consideration and 

approval of the project and had a nationally recognized subject matter 

expert and two experts in research methodology and animal use 

alternatives separately review the materials for each project. In all 24 

protocols, investigators provided explanations of why they planned to use 

animals to meet research objectives. In 18 of the 24 protocols, 

investigators provided detailed discussions of the reasons for using 

animals, including reasons why proposed research could not be done using 

nonanimal models such as cell cultures or computer models. For example, 

the investigator on a study of a new type of skin graft justified the use of 

animals by explaining that cell cultures could not be used to determine the 

success of these grafts in treating burns and that animals were needed to 

assess the immune system’s response to the grafts. Documenting the 

consideration of replacement alternatives became a requirement when 

DOD adopted its standard protocol in fiscal year 1996. This documentation 

is intended to assist reviewers’ ability to determine the quality of 

investigators’ consideration of replacement alternatives.

In two protocols, investigators identified and incorporated nonanimal 

models as ways to reduce, though not totally replace, animal use. For 
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example, in one protocol, the investigator proposed to use cell cultures to 

screen vaccines before they were tested on mice. This process was 

designed to reduce the number of vaccines used on the mice, thus reducing 

the number of mice required. 

Investigators’ explanations for the proposed use of a specific animal 

species usually focused on why the species was most appropriate to meet 

research objectives. The specificity with which protocols addressed this 

issue varied widely, reflecting differences in facilities’ protocol forms. For 

example, justifications ranged from check marks on a standard checklist of 

reasons why the animals might be used to detailed discussions of the 

advantages of using the requested species. One protocol we reviewed 

contained a detailed discussion of why monkeys and dogs were the best 

species for the proposed experiments and why rodents, as an alternative 

lower-order species, were not as well-suited. This discussion was 

supported by an extensive bibliography. In addition, four of the six 

biological warfare defense protocols we reviewed proposed using monkeys 

and provided written justification explaining that a monkey’s response to 

biological warfare agents is similar to a human’s. Similarly, the use of pigs 

in several research protocols exploring resuscitation treatments was 

proposed because pigs have a cardiovascular system similar to that of 

humans.

The protocols we reviewed also showed consideration of the number of 

animals being proposed for use in the research. We found cases in which 

investigators incorporated methods to reduce the number of animals. In 

one protocol, the investigator planned to use historical data from previous 

experiments rather than using additional animals as a basis for 

comparison. In another protocol, the investigator designed the study to use 

one animal control group with two experimental groups of animals instead 

of a separate control group for each experimental group. In a third 

protocol, the investigator planned to use an alternative statistical technique 

that would reduce the number of animals needed while still achieving 

statistically valid results. In addition, since fiscal year 1996, investigators at 

DOD facilities have been required to certify that statisticians have reviewed 

proposed research to help ensure that the lowest number of animals as 

possible is used consistent with research objectives. Investigators at 

non-DOD facilities are required to provide similar information in their 

proposals to DOD. 

We found one project in which the number of animals could have been 

reduced, had the investigator reversed the sequence of proposed animal 
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procedures. In this case, the investigator planned to first measure the 

accuracy of an ingestible device in detecting the onset of traumatic shock 

in pigs. He then planned to assess how long the device would remain 

effective in the digestive systems of monkeys, whose digestive system is 

similar to humans’. The investigator planned to wound the pigs but not the 

monkeys. The investigator requested and received approval to test 400 pigs 

but not the monkeys. We believe that the monkeys should have been tested 

first because had the device not remained effective in the monkeys’ 

digestive systems, experiments on the pigs would not have been necessary. 

However, DOD subsequently terminated funding for this project due to 

budget reductions, and the second component involving the monkeys was 

never conducted. A service-level veterinarian agreed with us that it would 

have been preferable to have first tested the monkeys.

Protocols Addressed 

Refinements but More 

Could Have Been Done

All the protocols we reviewed described refinements to be used as required 

to alleviate pain. However, we found that other refinement alternatives 

were available and could have been used in 8 of the 24 protocols. We were 

unable to determine the extent to which these refinements were 

considered because documentation was generally lacking. 

All the protocols we reviewed described procedures for administering pain 

relief to animals as required and euthanizing them when appropriate. In 

addition, the investigator of one project on experimental burn treatments 

identified alternative anesthetics and analgesics to be used to improve pain 

relief for animals. In another case, the IACUC required that the investigator 

reduce animals’ pain and distress by euthanizing them earlier than the 

investigator had proposed. In this study of burn treatments, the IACUC 

required the investigator to euthanize rats when their body temperature 

dropped 4 degrees because scientific literature had demonstrated that such 

a temperature drop indicates impending death. The investigator had not 

proposed euthanizing the rats until later. Subsequent to approval of the 

protocol for this research, the IACUC issued a written policy requiring 

investigators to consider this alternative when preparing protocols. 

In contrast, we found that other refinement alternatives were available and 

could have been used in 8 of the 24 protocols. In five of these, the 

alternative was a refinement in the administration of pain relief to animals 

subjected to burns. In these protocols, sheep, pigs, rats, and mice were to 

be anesthetized while third-degree burns were being administered. 

However, the investigators did not plan to give the animals analgesia 

routinely after the burns. Investigators or attending veterinarians were to 
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monitor animals for behavioral changes usually associated with pain or 

distress such as postural changes, ruffled hair coat, and lack of appetite 

before administering analgesia. DOD officials stated that in general, pain 

relief was not needed after the burns were administered because the burns 

were limited to a well-defined area where the nerve endings had been 

destroyed by the burns, resulting in no pain.

Whether analgesia should be administered on a routine or as-needed basis 

in these situations is controversial. Experts and non-DOD officials 

involved in regulating animal research told us that in experiments such as 

these, animals can experience pain around the periphery of the burned area 

and should be given analgesia routinely after burns are administered. They 

also pointed out that it can be difficult to identify pain in animals and that if 

the results of the research would not be compromised, routine 

administration of analgesia is warranted as a preventive measure. DOD 

officials acknowledged that there is uncertainty over the issue.

Given this controversy, we believe that investigators and IACUCs should 

fully consider the appropriateness of analgesia administration in similar 

studies. Neither the investigators’ protocols nor the IACUC records, 

however, contained information on whether refinements involving the 

routine administration of analgesia had been considered. For example, at a 

non-DOD facility where one of these five studies was conducted, the 

IACUC record of consideration consisted only of the protocol number, 

which was listed among over two dozen protocols approved at one 

meeting, and brief notes on additional information requested by the IACUC. 

None of the requested information concerned the use of analgesia. 

Similarly, at another facility we visited, the Association for Assessment and 

Accreditation of Laboratory Animal Care International, an independent 

accreditation organization,12 found that the IACUC did not adequately 

document that pain and distress were addressed in the protocol approval 

process. DOD’s standard protocol format, which was implemented in fiscal 

year 1996, does not require investigators to discuss refinement alternatives 

that are considered but not adopted.

Other refinement alternatives could have been implemented in the sixth 

and seventh projects. In these projects, mice that had been given a toxin 

could have been euthanized sooner, on the basis of a drop in their body 

temperature, without compromising the research results. The presence of 

12 DOD requires that all of its facilities apply for AAALAC accreditation.
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Page 16 GAO/NSIAD/HEHS-99-156 DOD Animal Research

hypothermia (low body temperature) as an objective indicator of 

impending mortality for this type of toxin was published as early as 1992, 

before the development of both protocols.13 Although evidence of the 

effectiveness of this measurement approach was available and was 

employed in one of the other protocols we reviewed, DOD officials said 

that the validity of the evidence had not yet been demonstrated on different 

types of research and species of animals. Researchers at Army laboratories 

recently conducted two studies to investigate the hypothermia-based 

end-point indicator. While one of the studies confirmed a correlation 

between lowered body temperature and mortality, the other was unable to 

identify a similar correlation. None of the records we reviewed contained 

information on investigators’ or IACUCs’ consideration of this refinement.

In the eighth protocol, an alternative vaccine could have been used in a 

study testing the effectiveness of a vaccine to protect monkeys from a 

potential biological warfare agent. In this study, monkeys that had been 

treated with an experimental vaccine against staphylococcal enterotoxin B 

were exposed to the toxin. The vaccine was prepared from the toxin and, 

as a result, had a greater likelihood of having side effects that could cause 

pain and distress to the monkeys than a vaccine prepared using a 

recombinant technique. Research had been published as early as 3 years 

before this protocol was prepared pointing to the availability of 

recombinant techniques for developing a vaccine against this toxin.14 

However, the protocol and IACUC records did not address this alternative.

Identifying Alternatives Is 

Challenging

Finding alternatives that can be used in research is challenging for 

investigators. These challenges affect all research, whether it is funded by 

DOD or by other public or private organizations. Although DOD requires 

investigators to conduct a literature search to identify alternatives to 

painful procedures, literature searches may not capture all the possible 

alternatives, in part because the literature may not specifically identify 

alternatives. For example, an investigator may have used an innovative 

type of anesthesia on animals but may not have discussed the procedure in 

the published results of the research. Because alternatives cut across 

13 Soothill, J.S., Morton, D.B., and Ahmad, A., “The HID50 (hypothermia-inducing dose 50): an alternative 

to the LD50 for measurement of bacterial virulence,” International Journal of Experimental Pathology

(Feb. 1992), pp. 95-98.

14 Harris, T.O., et al., "Lack of complete correlation between emetic and T-cell-stimulatory activities of 

staphylococcal enterotoxins," Infection and Immunity (Aug. 1993), pp. 3175-3183.
B-278778.1

Page 17 GAO/NSIAD/HEHS-99-156 DOD Animal Research

many fields of research, investigators need to search numerous sources, 

including some abroad, to find available information on alternatives. 

The universe of alternatives is broad and changes constantly. An 

alternative can be as narrow as a better form of anesthesia and as broad as 

cell cultures and computer models which do not use animals at all. At the 

same time, scientific advances can lead to the development of new 

alternatives. One example is the development of nonanimal procedures for 

the production of monoclonal antibodies. Previously, these antibodies 

were produced primarily using animals such as mice but they can now be 

produced using cell culture techniques.

AWIC and the Center for Alternatives to Animal Testing15 are working on 

projects, supported by the Office for Protection from Research Risks 

(OPRR) of the National Institutes of Health, designed to help improve the 

usefulness of literature searches for alternatives by making it easier to find 

alternatives among the numerous online sources. OPRR has entered into 

an agreement with AWIC to develop an interactive Internet-based training 

program on searching for alternatives. The program will be based on 

AWIC’s existing training program on literature searching for alternatives. 

Also, OPRR has been working with the Center for Alternatives to Animal 

Testing to explore the development of a comprehensive search engine for 

the numerous electronic sources of information on alternatives. These 

efforts could assist all researchers, including DOD-funded investigators, to 

more effectively and efficiently identify alternatives. 

In addition, continuing review of protocols at some facilities could be more 

rigorous. While the facilities we visited generally had procedures in place 

to ensure that IACUCs reviewed and approved significant changes to 

protocols after research had begun and conducted periodic reviews of 

investigators’ progress in completing their protocols, we found instances in 

which investigators and IACUCs could have more closely addressed 

alternatives. One protocol at a non-DOD facility underwent numerous 

major changes after it was originally approved by the institution’s IACUC. 

The scope of the project was expanded to inflict injuries on different parts 

of pigs’ bodies, change pain killers used on the pigs, and assess different 

resuscitation treatments on the pigs. We found no evidence in the amended 

15 This center, based at Johns Hopkins University in Baltimore, Maryland, operates the ALTWEB 

Internet site, which provides links to numerous sources of information on animal use alternatives. 
B-278778.1

Page 18 GAO/NSIAD/HEHS-99-156 DOD Animal Research

protocols or IACUC records we obtained that alternative procedures were 

considered. 

In an experiment at a DOD facility to develop field techniques for 

resuscitating severely injured servicemembers, the first 14 of 21 pigs (67 

percent) that were tested died unexpectedly. Because it was concerned 

about the high ratio of deaths, the IACUC considered and approved 

changes intended to reduce the risk of death from the surgical procedures. 

But in a later phase of the experiment, 11 of 28 pigs (39 percent) died, in 

part because of the inexperience of a project member who performed the 

surgical procedures. In a memo explaining these deaths to the facility’s 

IACUC, the investigator set the goal of reducing the mortality rate in this 

experiment to not more than 20 percent. The investigator put in place 

provisions (such as additional training for surgical staff) intended to 

correct the problems that caused these deaths. Although we found 

evidence that the IACUC was responsive to the unexpected deaths, which 

occurred over a period of several years, it acted only after a high number of 

deaths had occurred. However, the IACUC subsequently implemented a 

policy requiring investigators to report any unexpected deaths within 48 

hours. 

Conclusions DOD’s controls on animal use were generally effective but improvements 

are needed. Although we were able to link virtually all animal use projects 

to military objectives, DOD lacks centralized information on the military 

justification for each project. Without such information, neither Congress 

nor the public have an adequate basis for understanding and assessing the 

reasons DOD uses animals in its research. We continue to believe that 

DOD should implement our previous recommendation to improve the 

information reported on individual projects that use animals.

DOD implemented several procedures that worked well to avoid 

unnecessary duplication by the 24 projects we reviewed. We did not find 

unnecessary duplication by any of these projects. However, the process for 

assessing duplication could be improved further. DOD has not adequately 

defined what it considers appropriate databases for literature searches. We 

are concerned that as a result, investigators at non-DOD facilities may not 

routinely search databases such as FEDRIP and DTIC that provide 

information on government research in progress. Information on ongoing 

research is important to help investigators identify the potential for 

unnecessary duplication. 
B-278778.1

Page 19 GAO/NSIAD/HEHS-99-156 DOD Animal Research

DOD was generally successful in considering and implementing 

replacement and reduction alternatives in the 24 research projects we 

reviewed. However, we found additional refinements that could have been 

implemented in one-third of these projects. We recognize the challenges 

that investigators and IACUC members face in identifying alternatives, 

especially because scientific literature does not always discuss alternatives 

and scientific and veterinary practices change rapidly. Furthermore, 

uncertainty remains over the need to use some alternatives such as the 

routine administration of analgesia in burn studies. However, we were 

unable to determine the extent to which the refinements we identified were 

considered by investigators and IACUCs because protocols and IACUC 

records did not document the alternatives that were considered but not 

adopted. DOD has adopted a standard protocol requiring investigators to 

discuss replacement alternatives considered but not adopted. A similar 

requirement to document the refinement alternatives that were considered 

could encourage investigators to focus more on these alternatives and 

provide IACUCs better information on alternatives when they review 

protocols.

 Recommendations To further reduce the likelihood of proposed research unnecessarily 

duplicating other research, we recommend that the Secretary of Defense 

clarify DOD’s policy regarding which databases of research in progress 

investigators must search. We also recommend that the Secretary further 

facilitate the consideration of refinement alternatives by investigators and 

IACUCs. Specifically, the DOD standard animal use protocol form should 

be amended to require investigators to identify refinement alternatives that 

were considered but not adopted and explain why they were not adopted.

Agency Comments In written comments on a draft of this report (see app. III), DOD concurred 

with our recommendations. DOD stated that it will clarify the databases 

that should be searched for research in progress and will amend the 

standard protocol to identify refinement alternatives that were considered 

but not adopted and to explain why specific alternatives were not adopted. 

DOD raised a concern about the title of the report, saying it should be 

changed by replacing the word “needed” with “suggested.” DOD believed 

that the term “needed” implies that improvements are required or 

necessary to meet a standard, and noted that our report did not present 

instances in which federal standards were not met. While we found no 
B-278778.1

Page 20 GAO/NSIAD/HEHS-99-156 DOD Animal Research

evidence that DOD failed to meet federal standards, the changes we are 

recommending are necessary to guard against unnecessary duplication and 

to promote the implementation of alternatives in DOD's projects that utilize 

animals. DOD also included technical comments in its response which we 

incorporated where appropriate.

We are sending this report to the Honorable William Cohen, Secretary of 

Defense and other interested parties. We will also make copies available to 

others upon request.

If you have any questions about this report, please call Kwai-Cheung Chan 

at (202) 512-3092 or Stephen P. Backhus at (202) 512-7101. GAO contacts 

and staff acknowledgements are listed in appendix IV. 

Kwai-Cheung Chan

Director, Special Studies and Evaluations

National Security and International Affairs Division

Stephen P. Backhus

Director, Veterans’ Affairs and Military Health Care Issues

Health, Education, and Human Services Division
B-278778.1

Page 21 GAO/NSIAD/HEHS-99-156 DOD Animal Research
Page 22 GAO/NSIAD/HEHS-99-156 DOD Animal Research

Contents

Letter 1

Appendix I

Scope and 

Methodology

24

Appendix II

DOD’s Process for 

Reviewing Animal 

Research Proposals

28

Appendix III

Comments From the 

Department of Defense

31

Appendix IV

GAO Contacts and 

Staff 

Acknowledgements

33

Related GAO Products 36

Tables Table 1: DOD Animal Use Objectives (fiscal year 1996) 6

Table I.1: Research Facilities Included in Study 26

Figure Figure II.1: DOD’s Process for Reviewing Animal Research Protocols

in Fiscal Year 1996 28
Contents

Page 23 GAO/NSIAD/HEHS-99-156 DOD Animal Research

Abbreviations

AFRRI Armed Forces Radiobiology Research Institute

AWIC Animal Welfare Information Center

BRD Biomedical Research Database

DARPA Defense Advanced Research Projects Agency

DOD Department of Defense

DTIC Defense Technical Information Center

FEDRIP Federal Research in Progress

IACUC Institutional Animal Care and Use Committee

OPRR Office for Protection from Research Risks
Page 24 GAO/NSIAD/HEHS-99-156 DOD Animal Research

Appendix I

Scope and Methodology ApIenxdi

Our objectives were to determine to what extent projects using animals 

funded or performed by the Department of Defense (DOD) (1) were 

directed toward military objectives; (2) unnecessarily duplicated other 

research; and (3) incorporated alternatives that reduced, replaced, or 

refined the use of animals.

To assess the extent to which animal use projects were directed toward 

military objectives, we used the Biomedical Research Database (BRD) to 

identify the universe of projects using animals being conducted by DOD. 

We used the fiscal year 1996 BRD because it contained the most current 

summary information on animals used in research, education, training, and 

testing at the time we began our review.1

 This database covered 805 animal 

use projects conducted by DOD and the military services. 

Because the BRD does not include information about military objectives 

for each project, we collected this information from the 16 DOD program 

offices that sponsor animal use projects. We asked officials there to 

identify the specific service-level research objectives linked to each 

project. We reviewed documentation, where available, to confirm their 

assessments. For other projects, we relied on officials’ assessments, which 

were based on their knowledge of the projects that had been conducted. 

We also interviewed DOD officials in 14 offices that have responsibility for 

developing military research objectives and policies for clinical 

investigations and reviewed policies and reports. 

To address our second and third objectives, we reviewed legislation and 

regulations related to the welfare of research animals and relevant DOD 

policy documents and directives. We reviewed published literature on 

animal use issues and attended conferences on this subject. We 

interviewed veterinarians and others who manage DOD’s laboratory animal 

use programs. We also met with representatives from government 

agencies, accrediting organizations, animal welfare groups, and others, 

including the:

Animal Plant and Health Inspection Service, United States Department of 

Agriculture (USDA);

Animal Welfare Information Center, USDA; 

1

 The BRD does not include information on DOD’s use of animals for human or animal consumption, 

ceremonial activities, and recreation or its training, care, and use of military working animals. 
Appendix I

Scope and Methodology

Page 25 GAO/NSIAD/HEHS-99-156 DOD Animal Research

National Institute of Environmental Health Sciences, National Institutes of 

Health (NIH), Department of Health and Human Services (DHHS);

Office for Protection from Research Risks, NIH, DHHS;

American College of Laboratory Animal Medicine;

Association for Assessment and Accreditation of Laboratory Animal Care 

International;

Humane Society of the United States;

In Defense of Animals;

Physicians Committee for Responsible Medicine;

Center for Alternatives to Animal Testing, Johns Hopkins University;

National Association for Biomedical Research; and

Institute of Laboratory Animal Research, National Academy of Sciences.

To review research projects, we selected projects from three areas of DOD 

research: treatment of injuries from biological weapons, combat casualty 

care, and treatment of radiation wounds. These three areas included 175 of 

the 805 fiscal year 1996 projects. They are areas of research in which 

animals are often injured or exposed to potentially deadly agents and in 

which the animals often either die of their wounds or are euthanized at the 

conclusion of the study. These areas also included a large proportion of 

projects that used higher-order animals such as nonhuman primates. We 

did not review projects in other areas where animals are used such as 

infectious diseases, chemical defense, human systems technology, and 

training and education.

From the 175 projects in the three areas we selected, we judgmentally 

selected 24 projects to review in depth. We selected projects that used 

large numbers of animals. In selecting specific projects, we also tried to 

include a wide range of species of animals, a mixture of DOD and non-DOD 

facilities, and several military services and Defense agencies. Seven of the 

24 projects used nonhuman primates and 12 used pigs, dogs, sheep, or 

rabbits. The other projects used large numbers of rodents. The projects in 

our sample included research performed at seven DOD laboratories and 
Appendix I

Scope and Methodology

Page 26 GAO/NSIAD/HEHS-99-156 DOD Animal Research

seven non-DOD facilities. Twelve of the 24 projects were sponsored by the 

Army; 5 were sponsored by the Navy; and 7 were sponsored by Defense 

agencies (the Armed Forces Radiobiology Research Institute, the Defense 

Advanced Research Projects Agency, and the Uniformed Services 

University of the Health Sciences). Air Force projects were not included 

because the BRD did not list the Air Force as a sponsor of projects in these 

areas of research. 

We visited the 14 facilities where the 24 projects were conducted (see

table I.1).

Table I.1: Research Facilities Included in Study

Funding agency or department in parentheses

Facility Location

Number of

projects

Department of Defense facilities

Armed Forces Radiobiology Research 

Institute 

Bethesda, Maryland 3

U.S. Army Institute of Surgical Research San Antonio, Texas 4

U.S. Army Medical Research Institute of 

Infectious Diseases

Frederick, Maryland 3

Naval Medical Center San Diego, California 1

Naval Medical Research Institute Bethesda, Maryland 2

Uniformed Services University of the 

Health Sciences

Bethesda, Maryland 2

Walter Reed Army Institute of Research Washington, District of Columbia 2

Non-DOD facilities 

Childrens Hospital Medical Center 

(Defense Advanced Research Projects 

Agency)

Cincinnati, Ohio 1

Massachusetts General Hospital (Army) Boston, Massachusetts 1

Naval Blood Research Institute, Boston 

University (Navy)

Boston, Massachusetts 1

University of Arizona (Army) Tucson, Arizona 1

University of North Carolina (Army) Chapel Hill, North Carolina 1

University of Tennessee Health 

Sciences Center (Navy)

Memphis, Tennessee 1

University of Virginia (Defense 

Advanced Research Projects Agency)

Charlottesville, Virginia 1
Appendix I

Scope and Methodology

Page 27 GAO/NSIAD/HEHS-99-156 DOD Animal Research

We reviewed documentation for each project to assess the protocol 

development and review processes. The review included acquiring and 

reviewing each research project’s animal use protocol; Institutional Animal 

Care and Use Committee (IACUC) records for these protocols; IACUC 

correspondence; institutional policies, procedures, and training materials; 

and correspondence between DOD reviewing officials and the investigator. 

Among those we interviewed at the facilities were past and current IACUC 

chairs, attending veterinarians, and other officials. We also interviewed 

investigators of 18 of the 24 research projects and nonaffiliated IACUC 

members at 11 of the 14 facilities.

We contracted with the USDA’s Animal Welfare Information Center (AWIC) 

to obtain an independent search of scientific literature relevant to each 

project. Each project was reviewed by three experts. We contracted with 

four subject matter experts, who reviewed projects in their areas of 

expertise. Also, we contracted with an expert in laboratory animal 

medicine and an expert in the field of alternatives to review all the projects. 

For each project, the experts reviewed research protocols, related 

documents, and the AWIC literature search. They provided comments that 

we considered when developing our findings on unnecessary duplication 

and alternatives. Our findings are not generalizable to all DOD research 

that used animals in fiscal year 1996.

We performed our work from October 1997 to May 1999 in accordance with 

generally accepted government auditing standards.
Page 28 GAO/NSIAD/HEHS-99-156 DOD Animal Research

Appendix II

DOD’s Process for Reviewing Animal 

Research Proposals ApxIendi

DOD’s process to reduce unnecessary duplication and promote alternatives 

to animal use relies on investigators to prepare detailed plans of their 

research—called protocols—and several levels of review of these 

protocols (see fig. II.1). The facilities we visited generally followed similar 

practices, with minor variations.

Figure II.1: DOD’s Process for Reviewing Animal Research Protocols in Fiscal Year 1996

Protocol Development In October 1995, DOD implemented a standardized protocol format for use 

by its facilities and required non-DOD facilities to address the information 

contained in the format. DOD implemented this format in response to 

recommendations by the Inspector General, who found that each research 

facility differed in the information it collected on proposed research. Of 
Appendix II

DOD’s Process for Reviewing Animal 

Research Proposals

Page 29 GAO/NSIAD/HEHS-99-156 DOD Animal Research

the 24 studies we reviewed, 4 of the 5 that were developed after October 

1995 used the new protocol format. The other protocols were developed 

prior to 1995 and used different formats. 

The standard protocol format requires that investigators address several 

elements, including the study background, objectives and hypotheses, 

military relevance, experimental design, animal requirements and 

justifications, research procedures, veterinary care, investigator 

qualifications, and safety issues. In the protocols, investigators are 

required to provide written assurance that the proposed research does not 

unnecessarily duplicate other studies. This requirement stems from animal 

welfare regulations. In addition, DOD requires that its investigators review 

specific electronic databases to identify whether the proposed research 

could unnecessarily duplicate other studies; document the results of their 

search; and identify the databases searched, key words used, and the dates 

of the search. Investigators must present written justification for the use of 

animals, to include consideration of nonanimal alternatives, the total 

number and species of animals to be used, and alternatives being 

employed. 

Review and Approval of 

Animal Use Protocols

DOD requires that each protocol pass through several review steps before 

animals are used: a scientific review, a facility-level review by an IACUC 

and, for many protocols, a DOD veterinary review. A scientific merit 

review is conducted by the DOD funding organization to determine 

whether the research is likely to contribute to the advancement of 

scientific knowledge and military objectives. Generally, scientific merit 

reviews for DOD facilities are conducted by in-house scientists. Scientific 

merit review for research at non-DOD facilities varies depending on the 

funding agency. For example, the U.S. Army Medical Research and 

Materiel Command conducts scientific merit reviews for projects proposed 

by investigators at non-DOD facilities by contracting with scientists who 

are not affiliated with the command or the facility. On the other hand, the 

Office of Naval Research uses in-house scientists to conduct scientific 

reviews of its research at non-DOD facilities. 

Proposals that pass scientific review are then reviewed by the research 

facility’s IACUC. The IACUC review is critical to the entire process 

because IACUC approval is required before funding is allocated and 

animals can be ordered or used. The IACUC conducts a review of the 

protocol to ensure compliance with animal welfare laws and regulations. 

Although minutes of the review meetings are maintained, detailed 
Appendix II

DOD’s Process for Reviewing Animal 

Research Proposals

Page 30 GAO/NSIAD/HEHS-99-156 DOD Animal Research

documentation of issues discussed in the consideration of protocols is not 

required.

Under certain circumstances, DOD requires a third level of review. If a 

proposal calls for using nonhuman primates, DOD requires that a 

service-level veterinarian trained or experienced in laboratory animal 

science and medicine perform a review. The purpose of this review is to 

ensure that the investigator and the institution where the research is to be 

conducted are in compliance with the Department of Health and Human 

Services’ guidance on the supply and use of laboratory primates.1

 In 

addition, DOD requires that these reviewers examine all projects at 

non-DOD facilities, regardless of the species used, for compliance with 

animal welfare and DOD requirements. The Army requires a similar type of 

review for protocols at its facilities that propose to use dogs or cats. 

Post-approval Review of 

Research

Once the research has begun, the IACUC annually reviews each protocol. 

The purpose of the annual review is to determine whether the project 

should continue. The annual protocol report describes the project’s status 

(e.g., active, terminated) and any significant changes made to the protocol 

during the year. In addition, if investigators wish to amend the protocol 

during implementation of their research, they must obtain approval from 

the IACUC before making changes. The nature of the IACUC’s review 

depends on the significance of the change. IACUCs often delegate 

approval for minor modifications such as a change in the dosage of a drug 

being administered to the veterinarian member of the IACUC. A major 

modification such as a change in number of animals to be used generally 

necessitates a formal review by the IACUC.

1

 National Primate Plan, U.S. Department of Health and Human Services, NIH-80-1520 (Oct. 1978).
Page 31 GAO/NSIAD/HEHS-99-156 DOD Animal Research

Appendix III

Comments From the Department of Defense ApIenxdi
Appendix III

Comments From the Department of Defense

Page 32 GAO/NSIAD/HEHS-99-156 DOD Animal Research

Now on p. 19.

Now on p. 19.
Page 33 GAO/NSIAD/HEHS-99-156 DOD Animal Research

Appendix IV

GAO Contacts and Staff Acknowledgements ApIVexndi

GAO Contacts John Oppenheim, (202) 512-3111

Bruce D. Layton, (202) 512-6837

Acknowledgements In addition to those named above, Jaqueline Arroyo, Dan Engelberg, Cary 

Russell, and Gregory Whitney made key contributions to this report.
Page 34 GAO/NSIAD/HEHS-99-156 DOD Animal Research
Page 35 GAO/NSIAD/HEHS-99-156 DOD Animal Research
Page 36 GAO/NSIAD/HEHS-99-156 DOD Animal Research

Related GAO Products

DOD Animal Research: Improvements Needed in Quality of Biomedical 

Research Database (GAO/NSIAD/HEHS-99-24, Dec. 14, 1998).

Biological Warfare: Better Controls in DOD’s Research Could Prevent 

Unneeded Expenditures (GAO/NSIAD-91-68, Dec. 27, 1990).

Army Biomedical Research: Concerns About Performance of Brain-Wound 

Research (GAO/HRD-91-30, Dec. 12, 1990).

(713013) Letr
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Table 1: DOD Animal Use Objectives (fiscal year 1996) 6

Table I.1: Research Facilities Included in Study 26
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Figure II.1: DOD’s Process for Reviewing Animal Research Protocols in 

Fiscal Year 1996 28