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Appendix B U.S. Department of Agriculture Statistics on the Use of Dogs and Other Animals in Research The U.S. Animal Welfare Act of 19661 (AWA) mandated that the U.S. Department of Agriculture (USDA) collect annual reports listing the numbers of vertebrate animals (excepting mice, rats, and birds) used by all USDA-registered academic and industrial research facilities, as well as federal research facilities,2 including the U.S. Department of Veterans Affairs (VA). Reports from individual facilities to the USDAâs Animal and Plant Health Inspection Service (APHIS) are publicly available (USDA AHPIS, n.d.a), as are annual summaries of regulated animal use by state (USDA APHIS, 2020). For USDA purposes, âresearchâ includes teaching, testing, and research; hence, these numbers include all AWA-regulated species used by academic, industrial (public or private), and government research facilities engaged in professional training, biomedical research, or product development/safety testing while excluding animal breeding and other activities related to the pet industry. The USDA AWA data also include animals that were bred for research but have not yet been used. Hence, the USDA AWA statistics provide the most complete and detailed view of trends in total and individual species usage for research (excluding mice, rats, and birds) within the U.S. research enterprise over the past 45 years. Using data from the USDA web site (USDA APHIS, 2020) for the years 2008â2018 and from archived annual reports (USDA APHIS, n.d.b) for prior years, the committee investigated trends in the use of dogs and other regulated species from 1973 to 2018, the results of which are summarized in Figure B-1. USDA AWA data on total regulated animal use reveal the following trends over the last 45 years: 1. There was a substantial decrease in dog use from 1973â2018 (see Figure B-1). Dog use peaked at more than 200,000 per year in the late 1970s to early 1980s and then entered a 20-year period of decline. By the early 21st century, dog usage plateaued at roughly 60,000 per year, representing a 65 percent decrease from prior peak levels. This level of annual dog use has remained relatively stable over the past two decades. 2. Within the same time period, use of cats, guinea pigs, hamsters, rabbits (1973â2007), and farm animals (1990â2007) also decreased by 50 percent or more (data not shown). 3. Indeed, the only categories to increase over this period were non-human primates and âother covered species.â 4. Total reported animal usage among all AWA-covered species was 1,653,345 in 1973, 1,027,450 in 2007, and 780,080 in 2018. 1 U.S. Code Title 7 Chapter 54: Transportation, sale, and handling of certain animals. Available at https://www.nal.usda.gov/awic/animal-welfare-act (accessed on December 30, 2019). 2 Federal research facilities are exempt from USDA registration but required to file the same animal use reports as registered facilities. 156 Prepublication Copy: Uncorrected Proofs
Appendix B FIGURE B-1 Annual dog, non-human-primate, and pig usage 1973â2018 in the United States, based on data collected by the U.S. Department of Agriculture. SOURCES: For 2008â2018, USDAâAPHIS (2020); for 1973â2007, USDAâAPHIS (n.d.b). INTERPRETATION OF TRENDS IN USE OF DOGS FOR RESEARCH The highest numbers of dogs (>200,000 per year) reported in USDA AWA statistics in the 1970s likely mark the maximum usage for such purposes in U.S. history.3,4 The decrease in dog use from the 1980s to 2000 coincides with the rapid rise of cellular and molecular disciplines, resulting in an unprecedented paradigm shift away from animal and tissue bioassays in the biological sciences (Kinter and DeGeorge, 2016). USDA data indicate that the decrease in dog use was not offset by a commensurate increase in use of non-human primates (NHPs), pigs, or other AWA covered species. Despite the decline in overall dog use for biomedical research since 1973, the use of both rodent and non-rodent species for regulated product testing has increased over the same period (Kinter and DeGeorge, 2016). Hence, most of the observed decrease in dog usage over the past 40 years likely reflects declines in use for basic and discovery research activities, as discussed in detail in Chapter 3, and the near elimination of the use of dogs for teaching (Simkin et al., 2017). It is noteworthy that NHP usage, while not approaching the historically high levels observed for dogs, has nonetheless demonstrated no downward trend from 1973â2018 and has increased steadily in recent years, reaching and even exceeding concurrent dog usage. This trend in the use of NHPs parallels an increase in the number of regulated products for which dogs and other non- primate species would be inappropriate subjects (for example, certain humanized-protein-based and nucleic-acid-based therapeutics). Some of the decrease in dog use over the past 40 years may have been compensated for by increasing the use of pigs for research purposes. Unfortunately, publicly available USDA AWA data did not provide pigs with a separate designation from farm animals until 2002. Nonetheless, pig use has been trending downwards since 2002 and is currently at approximately 50,000 per year, slightly lower than dog use. 3 L. B. Kinter, personal communication. This is a surmise based on extensive personal experience in the field. There was no formal requirement for recording animal usage prior to this period. 4 By comparison, this estimate is approximately 30 percent of the total number of dogs estimated killed annually in U.S. animal shelters. https://www.aspca.org/animal-homelessness/shelter-intake-and-surrender/pet-statistics (accessed on December 10, 2019). Prepublication Copy: Uncorrected Proofs 157
Necessity, Use, and Care of Laboratory Dogs at the U.S. Department of Veterans Affairs Guinea pig and rabbit usage were, respectively, approximately 409,000 and 448,000 in 1973 and 207,000 and 237,000 in 2007, far exceeding dog usage while showing comparable declines. However, the committee is aware that guinea pig and rabbit models have replaced some dog models for product testing during this period, of which drug-induced long QT syndrome is one example (Hamlin, 2007). Focusing on particular research uses for which dogs were once a dominant model, 10 of which are discussed in detail in Chapter 3, most (though not all) dog models have been replaced by smaller species, primarily rodents. For example, a literature search of the eight major cardiovascular research journals revealed that in the last 20 years, the overwhelming majority of papers reporting experimental animal models used rodents, mostly mice, which are not tracked by the USDA (Harrison, 2019). CURRENT DISTRIBUTION OF LABORATORY DOG USAGE AMONG RESEARCH INSTITUTIONS In an effort to better understand how dogs are currently being used in the United States, the committee reviewed the 1,149 annual reports submitted to APHIS under the AWA from all research facilities in all 50 states and territories in 2017, noting the number of dogs used by each type of reporting institution. To provide context for the dog usage data, the committee also collected 2017 usage data for two other laboratory animals: NHPs, which are commonly used as a surrogate for humans for phylogenetic reasons; and pigs, which are often considered a large-animal alternative to dogs. Procedure for Assessing Distribution of USDA-Regulated Dog Use To perform its analysis, the committee used a publicly available web site (USDA APHIS, n.d.a). This site enables the user to access all institutional APHIS reports filed in each state in a given year. When this analysis was initiated (in mid-2019), the most recent year with complete institutional reports was 2017. Committee members performed a state-by-state review of animal usage in 2017 to obtain total dog, pig, and NHP usage for each type of institution. This review was done in three steps. First, the USDA summary of each report was viewed, to determine whether any dog, pig, or NHP usage had been reported. Second, if usage of any of these species was non-zero, then the individual report was examined and the name of the reporting institution was recorded, along with its total dog, pig, and NHP usage (columns C + D + E in the report). Third, each institution was classified as either academic/hospital, company/private research organization, government agency (including VA), or non-research. For each state, the total dog usage obtained in the committeeâs analysis was checked by National Academies of Sciences, Engineering, and Medicine staff against the total provided by the USDA in its annual summary of 2017 data broken down by state (USDA APHIS, 2020). Wherever a discrepancy arose, the staff sought to correct it or determine its source. The sources of all discrepancies were determined, and totals were reconciled. In some cases, it was concluded that the discrepancies were due to small errors in USDA data calculating the total dog usage for a particular institution or state. As a result, the committeeâs sum of 60,190 dogs used in 2017 differs slightly from the total of 59,401 posted on the USDA web site as of the writing of this report (USDA APHIS, n.d.a). 158 Prepublication Copy: Uncorrected Proofs
Appendix B Results: Distribution of USDA-Regulated Dog Use in 2017 Of the 60,190 dogs reported to USDA as used under the AWA in 2017, 22,933 were reported by 213 academic institutions and affiliated hospitals engaging in biomedical research and education (including veterinary research conducted for the benefit of dogs); 34,875 by 105 companies and private research organizations engaging in applied biomedical research and product development, including testing required by regulatory agencies; 832 by 11 government agencies (including VA research labs) conducting basic and applied research in support of their missions; and 1,550 by 16 other, non-research groups (see Table B-1). The 2017 USDA data indicate that industry, defined as companies and private research organizations, is now the dominant user of dogs for biomedical research, exceeding the total usage by academia and government combined. The majority of industrial dog usage likely represents product safety testing designed and conducted by sponsors in fulfillment of regulatory requirements, as stipulated by the U.S. Food and Drug Administration (Kinter and DeGeorge, 2016), the U.S. Environmental Protection Agency (EPA, n.d.), other federal agencies, and international equivalents (Spielmann, 2002). These would include general toxicology studies required for the nonclinical development and product registration of pharmaceuticals and medical devices, agricultural and industrial chemicals, veterinary products, and household chemicals. The UK Home Office offered similar conclusions for experimental procedures performed in the United Kingdom using dogs in 2018 (Home Office, 2019). In the testing of pharmaceuticals for which the dog is selected as the nonrodent development species, a protocol that follows current guidelines will use approximately 150 dogs over 3 years, or 50 dogs per year per product (Kinter and DeGeorge, 2016). Hence, the entirety of 2017 USDA-reported dog usage by U.S. companies and private research organizations could be accounted for by roughly 700 active development projects. TABLE B-1 Usage of Dogs, NHPs, and Pigs Reported to USDA-APHIS in 2017 Animal Institution Type Reporting Institutions Animals Used in 2017 Dog Academic 213 22,933 Industry 105 34,875 Government 11 832 Non-Research 16 1,550 TOTAL 345 60,190 NHP Academic 104 28,859 Industry 46 37,906 Government 12 5,200 Non-Research 6 409 TOTAL 168 72,374 Pig Academic 192 25,447 Industry 104 20,256 Government 33 9,379 Non-Research 6 70 TOTAL 335 55,152 SOURCE: Publicly available data from the USDA (USDA APHIS, n.d.a) were analyzed as described in the text. Prepublication Copy: Uncorrected Proofs 159
Necessity, Use, and Care of Laboratory Dogs at the U.S. Department of Veterans Affairs In recent years, there has been increasing pressure on regulatory authorities and agencies to decrease the use of large animals in research (e.g., Grimm, 2019). The plateau in annual dog usage over the past 20 years is consistent with the fact that, despite this pressure, international requirements using non-rodent species (including dogs) in product development testing have increased, rather than decreased, over this period (Brock et al., 2013; Kinter and DeGeorge, 2016; van der Lann and DeGeorge, 2013). Distribution of USDA-Regulated NHP and Pig Use in 2017 Drawing on the same institutional animal reports used to determine the distribution of dog usage, the committee examined the distribution of both NHP and pig usage among types of institutions in 2017 in order to ask whether a significant amount of research using dogs had shifted to one of these other species (USDA APHIS, n.d.a.). In 2017, 46 U.S. industrial institutions reported using a total of 37,906 NHPs, exceeding the combined totals of 122 academic, government, and other institutions (see Table B-1). As noted above, the trend in use of NHPsâparticularly given their predominant use in industryâis consistent with an increasing number of regulated products for which dogs and other non- primate species would be inappropriate subjects. In 2017, 104 U.S. industrial institutions reported using a total of 20,256 pigs, compared with 25,447 pigs reported by 192 academic institutions and 9,379 by 33 government institutions (see Table B-1). Collectively, these numbers indicate (1) in the United States, dogs and NHPs are used primarily by industry to support product development; (2) the use of pigs lags behind that of dogs and NHPs in industrial organizations; and (3) academic and government institutions may have shifted some basic research activities away from dogs and NHPs to pigs. REFERENCES Brock, W. J., K. L. Hastings, and K. M. McGown (eds.). 2013. Nonclinical safety assessment: A guide to international pharmaceutical regulations. Chichester, UK: John Wiley & Sons. EPA (U.S. Environmental Protection Agency). n.d. Efforts to reduce animal testing at EPA. https://www.epa.gov/research/efforts-reduce-animal-testing-epa (accessed April 13, 2020). Grimm, D. 2019. U.S. EPA to eliminate all mammal testing by 2035. Science, September 10. https://www.sciencemag.org/news/2019/09/us-epa-eliminate-all-mammal-testing-2035 (accessed April 13, 2020). Hamlin, R. 2007. The guinea pig in cardiac safety pharmacology. Journal of Pharmacological and Toxicological Methods 55:1â2. Harrison, D. 2019. Presentation at the Committee on the Assessment of the Use and Care of Dogs in Biomedical Research Funded by or Conducted at the U.S. Department of Veterans Affairs Public Workshop on the Uses of Dogs in Biomedical Research, March 27, Washington, DC. Kinter, L. B., and J. J. DeGeorge, 2016. Scientiï¬c knowledge and technology, animal experimentation, and pharmaceutical development. ILAR Journal 57(2):101â108. Simkin, D. J., J. A. Greene, J. Jung, B. C. Sacks, and H. E. Fessler. 2017. The death of animals in medical school. New England Journal of Medicine 376(8):713â715. Spielmann, H. 2002. Animal use in the safety evaluation of chemicals: Harmonization and emerging needs. ILAR Journal 43(S1):S11âS17. USDA APHIS (U.S. Department of Agricultureâs Animal and Plant Health Inspection Service). n.d.a. Annual reports search. https://acis.aphis.edc.usda.gov/ords/f?p=118:205:0 (accessed April 10, 2020). 160 Prepublication Copy: Uncorrected Proofs
Appendix B USDA APHIS. n.d.b. Internet archive: Animal welfare report. https://archive.org/details/usda-animal welfarereport (accessed April 13, 2020). USDA APHIS. 2020. Research facility annual summary and archive reports. https://www.aphis.usda. gov/aphis/ourfocus/animalwelfare/sa_obtain_research_facility_annual_report/ct_research_facility_an nual_summary_reports (accessed April 10, 2020). van der Laan, J. W., and J. J. DeGeorge (eds.). 2013. Global approach in safety testingâICH guidelines explained. AAPS Advances in the Pharmaceutical Sciences series. New York: Springer. Prepublication Copy: Uncorrected Proofs 161