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Funding, Ethics, and Animal WelfareLast updated on February 24, 2002 Leadership of NIH, NCRR, USDA and AAALAC (potential exam fodder) Use of Recombinant DNA
Research FundingNIHOn January 1, 2000, Dr. Ruth Kirschstein was appointed the Acting Director of the National Institutes of Health. The previous Director, Dr. Harold E. Varmus, is now President and Chief Executive Officer of the Memorial Sloan-Kettering Cancer Center. Dr. Kirschstein served as the NIH deputy director between November 1993 and December 31, 1999. She also served as the acting NIH director between July 1993 and November 22, 1993. Prior to that, she was the director of NIGMS, beginning that appointment on September 1, 1974. From 1957 to 1972, Dr. Kirschstein performed research in experimental pathology at the Division of Biologics Standards (now the Center for Biologics Evaluation and Research, FDA). During that time, she helped develop and refine tests to assure the safety of viral vaccines for such diseases as polio, measles, and rubella. Her work on polio led to selection of the Sabin vaccine for public use. For her role, she received the DHEW Superior Service Award in 1971. In 1972 she became assistant director of the Division of Biologics Standards. That same year, when the division was transferred to the FDA as a bureau, she was appointed deputy director. She subsequently served as deputy associate commissioner for science, FDA, before being named NIGMS director. From September 1990 to September 1991, she was also acting associate director of the NIH for research on women's health. National Center for Research Resources, Comparative MedicineJohn Strandberg, D.V.M., Ph.D., Director, Comparative Medicine The Comparative Medicine (CM) area of the NIH National Center for Research Resources helps meet the needs of biomedical researchers for high quality, disease-free animals and specialized animal research facilities. The CM area--through grants, cooperative agreements, and contracts--supports regional primate research centers and their field stations, primate breeding and resource projects, development of both mammalian and non-mammalian animal models, postdoctoral training, and a variety of research projects. The CM area is composed of Regional Primate Research Centers, Laboratory Animal Sciences, Biological Models, AIDS Animal Models, and Research Manpower Development. USDASecretary of Agriculture: Ann M. Veneman W. Ron DeHaven, Deputy Administrator Jerry DePoyster, Senior Veterinary Medical Officer The U.S. Department of Agriculture's (USDA) Animal and Plant Health Inspection Service (APHIS) is committed to carrying out its responsibilities and meeting public expectations in its enforcement of two laws that seek to ensure the humane care and handling of animals: the Animal Welfare Act (AWA) and the Horse Protection Act (HPA). The AWA sets minimum standards of care and treatment for most warm-blooded animals bred for commercial sale, used in research, transported commercially, or exhibited to the public. The law was first passed in 1966, and was amended in 1970, 1976, 1985, and 1990. USDA enforces these laws through APHIS' Animal Care (AC) unit, which is headquartered in Riverdale, MD. Three regional offices in Raleigh, NC, Fort Worth, TX, and Sacramento, CA, are charged with enforcing the AWA and HPA in each of their respective regions. Each regional office employs field veterinary medical officers (VMOs) and animal care inspectors (ACIs). These employees are highly qualified, and have an excellent professional support system and communication network. Many also have specialized interest and expertise in such areas as the care of laboratory animals, zoo animals, or marine mammals.
NIH Grant Activity Codes
The Peer Review ProcessThe following information was obtained from http://grants.nih.gov/grants/policy/nihgps_2001/part_i_2.htm Competing applications for NIH grants and cooperative agreements, including those for competing continuations and competing supplements, are subject to peer review as required by sections 406 and 492 of the PHS Act or by NIH policy. The peer review system used by NIH, often referred to as the "dual review system," is based on two sequential levels of review for each application, initial review and National Advisory Council/Board review. The NIH peer review process has evolved over the years to accommodate changes in workload, resource constraints, and recommendations of various groups that have studied it. However, the underlying basis for the system—to provide a fair and objective review process in the overall interest of science—has not changed. Information concerning NIH's peer review process may be found at the following Web sites: http://www.csr.nih.gov and http://www.nih.gov/grants/peer/peer.htm. Information also is available by e-mail at DDER@nih.gov or GrantsInfo@nih.gov, or by calling, writing, or faxing a request to CSR. Initial ReviewThe Center for Scientific Review (CSR) is the receipt point for all competing grant applications submitted to NIH, whether the peer review will be conducted by CSR or by an IC. The primary determining factors in whether CSR or an IC will be responsible for the peer review are the solicitation type, the support mechanism, and/or the program. In general, CSR is responsible for the initial review of research project grant applications (including Academic Research and Enhancement Award (AREA) applications), National Research Service Award (NRSA) fellowship applications, and SBIR/STTR applications), while the ICs handle the initial review of conference grant applications, applications resulting from RFAs, and program project grant applications. CSR also may review other types of applications at IC request. When the IC is responsible for the initial review, CSR reviews the application for completeness, and the scientific review office of the soliciting IC reviews the application for responsiveness to the RFA, coordinates the initial technical review, and prepares the summary statements. CSR Referral Officers, who are senior health science administrators with both research and scientific review experience, assign each application to an IC(s) for potential funding and to a scientific review group for initial review of the scientific merit of the application. These determinations are made on the basis of the application's contents, the Referral Guidelines, and any written request by the applicant organization (accompanying the application) for a specific study section/IC assignment. Scientific review groups, including CSR study sections, are organized by scientific discipline or current research areas and are managed by health scientist administrators functioning as Scientific Review Administrators (SRA). Generally, study sections are chartered groups composed of formally appointed members serving multi-year terms, to which the SRA often adds temporary members or other additional reviewers. Special Emphasis Panels (SEPs) are formed on an ad hoc basis to review applications that cannot be reviewed by a standing review group or study section because they require special expertise or involve other special circumstances. The individuals serving on a scientific review group, whether a study section or SEP, are primarily scientists actively engaged in research. NIH's conflict-of-interest and confidentiality of information policies for reviewers are intended to ensure an unbiased review process by minimizing even the appearance of a conflict of interest and by restricting the use of privileged application information. Within 6 to 8 weeks following the established application receipt date, applicants are notified that the application has been received and are advised of the SRA, scientific review group, and IC assignments. At this time, applicants may request reconsideration of the review group and IC assignment. Once the assignment process is completed, the SRA is the contact for all communication with the applicant until the conclusion of the review group meeting. An applicant may withdraw an application from consideration at any time during the review process. A request to withdraw an application must be signed by the PI and an authorized organizational official. If an application is withdrawn before it enters the review process, CSR will return the application to the applicant. Applications withdrawn by the applicant after the beginning of the formal review may be destroyed by NIH or returned to the applicant at NIH's discretion. In preparation for the initial review, SRAs review applications to determine whether they are complete, conform to administrative requirements, and contain the information necessary for a detailed review. For each application, they then assign (from among the standing and temporary members) reviewers to write a critique of the application and readers to be prepared to discuss the application in detail. NIH uses "just-in-time" procedures for certain programs and award mechanisms. These procedures call for limited budget information to be submitted with the application (e.g., a budget justification and a modified biographical sketch) and allow for a possible NIH request for additional information, including information concerning other support, when the application is under consideration for funding. "Just-in-time" procedures also allow an applicant to defer certification of Institutional Review Board (IRB) approval of the project's proposed use of human subjects until after completion of the peer review and just prior to funding. (Applications in response to RFAs also may be subject to these procedures. The RFA will specify the timing and nature of required submissions.) For modular applications, the applicant is not required to submit detailed budget information with the application. In lieu of the standard budget forms, the applicant requests total direct costs for each year of support requested. The request must be accompanied by budget narrative for all personnel (by position, title, and level of effort), including consultants and "to be appointed" positions, and, when applicable, for consortium/contractual costs. NIH will request additional budget information in exceptional circumstances only. "Other support" information will be requested only for modular applications likely to result in an award. The goals of NIH-supported research are to advance the understanding of biological systems, improve the control of disease, and enhance health. Reviewers are asked to address, in their written comments, the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them, as appropriate, for each application. An application does not need to be strong in all categories to be judged likely to have a major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out work that, by its nature, is not innovative but is essential to move a field forward.
While the review criteria are intended for use primarily with unsolicited research project grant applications (e.g., R01s and P01s), including those in response to PAs, to the extent reasonable, they also will form the basis of the review of solicited applications and non-research activities. However, for some activities (e.g., construction grants), the use of these criteria, as stated, may not be feasible. Applications also may be reviewed against specific criteria as stated in RFAs or PAs. In addition to the above criteria, in accordance with NIH policy, all applications will be reviewed with respect to the following:
Following the initial review, the SRA prepares a summary statement for each application reviewed. The summary statement includes the reviewers' written comments, and, for scored applications, a summary of strengths and weaknesses, other summary highlights of the discussion, and a priority score. Summary statements are then provided to the IC's program staff and the PI. National Advisory Council or Board ReviewFor those applications recommended for further consideration, the summary statements are presented to the assigned IC National Advisory Council or Board (hereafter "Council") for use in the second level of review. Council members include both senior scientists with broad experience and members of the public with general knowledge of, and interest in, the IC's mission. The Council reviews applications not only for scientific and technical merit but also for relevance to the IC's programs and priorities. The Council may concur with the initial review group's recommendation, may decide not to recommend an application on the basis of program or policy considerations, or may recommend deferral of an application and refer it back to the initial review group for re-review. With very limited exception, an application may not be considered for funding unless it has received a favorable recommendation by both the initial review group and the Council. Recombinant DNA MoleculesThe NIH Guidelines for Research Involving Recombinant DNA Molecules (the NIH Guidelines) (65 FR 60328, October 10, 2000 or latest revision) apply to all NIH-funded and non-NIH funded gene transfer projects that are conducted at or sponsored by an organization that receives NIH support for recombinant DNA research. A copy of the NIH Guidelines is available at http://www.ncrr.nih.gov/publications/comparative_medicine/CARS.pdf. Extracts of the guidelines are on this Web site; click here. As defined by the NIH Guidelines, recombinant DNA molecules are either (1) molecules that are constructed outside of living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or (2) DNA molecules that result from the replication of those described in (1). The NIH Guidelines apply to both basic and clinical research studies. Specific guidance for the conduct of human gene transfer studies appears in Appendix M of the NIH Guidelines. Failure to comply with these requirements may result in suspension, limitation, or termination of NIH funds for recombinant DNA research at the organization or a requirement for NIH prior approval of any or all recombinant DNA projects at the organization. ...the NIH Guidelines should be carefully reviewed, in their entirety, to ensure compliance with all of the requirements for the conduct of projects involving recombinant DNA techniques. Animal WelfareThe PHS Policy on Humane Care and Use of Laboratory Animals (the Policy) requires that applicant organizations proposing to use vertebrate animals in NIH-supported activities file a written Animal Welfare Assurance with the Office of Laboratory Animal Welfare, NIH. The Policy, which defines "animal" as "any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes," stipulates that the applicant/grantee bears responsibility for the humane care and use of animals in NIH-supported research activities. The Policy implements and supplements the U.S. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training. It requires the applicant to establish appropriate policies and procedures for humane care and use of animals, based on the Guide for the Care and Use of Laboratory Animals, and to comply with the Animal Welfare Act and its implementing regulations. This includes appointment of an Institutional Animal Care and Use Committee (IACUC) with specified responsibilities. No NIH award for research involving live vertebrate animals will be made unless the applicant organization and all performance sites are operating in accordance with an approved Animal Welfare Assurance and provide verification that the IACUC has reviewed and approved those sections of the application that involve use of vertebrate animals, in accordance with the requirements of the Policy. Applications from organizations with approved Assurances will be considered incomplete if they do not include verification of IACUC review or do not contain the information concerning the use of vertebrate animals required as part of the application's research plan (see instructions for completion of the PHS-398 for the five specific points that need to be addressed). In the case of apparent or potential violations of the Policy, NIH may refer applications back to the applicant for further IACUC review. Foreign organizations proposing activities involving vertebrate animals are required to comply with the Policy or provide evidence that acceptable standards for the humane care and use of animals will be met. NIH will not make an award for research involving live vertebrate animals to an individual unless that individual is affiliated with an organization that accepts responsibility for compliance with the Policy and has filed the necessary assurance with OLAW. The Policy does not affect applicable State or local laws or regulations that impose more stringent standards for the care and use of laboratory animals. In addition, all organizations are required to comply, as applicable, with the Animal Welfare Act, as amended, 7 U.S.C. 2131 et seq., and other Federal statutes and regulations relating to animals. Information concerning the preparation and submission of Animal Welfare Assurances as well as copies of the Policy and other relevant materials are available from OLAW. Information concerning ways in which to reduce the administrative burden associated with these requirements also is available at OLAW web site http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-007.html Cost Analysis and Rate SettingIf the grantee operates an animal resource facility, charges for use of the facility should be determined in accordance with the Cost Analysis and Rate Setting Manual for Animal Research Facilities (May 2000), available from the National Center for Research Resources (NCRR) at its Web site: (http://www.ncrr.nih.gov/newspub/CARS.pdf) or from the NCRR Office of Science Policy and Public Liaison, 6705 Rockledge Drive, Bethesda, MD 20892-7965, (301) 435-0888, e-mail: ospio@ncrr.nih.gov. Identifying and Controlling Costs1. Cost Accounting A. How do we make money? "For cost analysis to be a basis for rate setting, all costs must be allocated to activities (or "cost centers") that produce a product or service for which a fee can be established." B. How do we spend money?, or, Basic Steps in "total cost accumulation"
2. Controlling costs Name some ways to economize in the animal facility:
Peaceable Kingdom, by Edward Hicks, 1833 EthicsMoral PhilosophiesUtilitarian Theory (consequentialism)
Utilitarianism depends upon the cost-benefit analysis: an action is "right" if it leads to the greatest possible good or to the least possible bad consequences for all affected parties. Peter Singer is a contemporary utilitarian who maintains that we must take into account the animals' own interests, in the same way we consider the interests of human infants or comatose patients. He is not entirely against animal research, having stated, "Those that do not involve, any, or very much, suffering for the nonhuman animals, and promise major benefits for humans or animals, may be defensible on utilitarian grounds." The key feature is whether a being is capable of suffering; if so, it has interests which are the same whether human or animal. Raymond Frey reaches different conclusions. He believes that the value of any life is contingent upon its quality, which is measured by its primary goods (i.e. living without pain and distress or living without physical boundaries). This leads to his conclusion that the lives of dogs, cats and chimps are more valuable than mice or rats. Singer and Frey both agree that the life of an adult chimp has more value than that of a human infant, because of the difference in "richness" of life. The species does not matter, only the quality or utility of one's life. This makes it more difficult to fully adopt utilitarianism as an ethos with regard to the use of animals in research.{4769} Kantian or Deontological TheoryDeontology is the study of moral obligation and responsibility, and does not require a balance of consequences; each action can be viewed independently as either right or wrong. Kantians can never treat a person as a means to one's own ends, so humans can only be used as research subjects if they give their informed consent. Kant believed that mistreating animals was wrong because it could lead eventually to violence against other humans. Tom Regan extended the concept of moral obligation to animals by arguing that animals have inherent value because they are "subjects of life." To Regan, animals may not be treated as resources for mankind. The capacity to experience life is unsurpassed in its moral standing. This philosophy is advocated by many animal rights advocates who oppose not only animal research, but also using animals for food or sport.{4769} Rights TheoryTo have a right is to be in a position to control what others are required to do, i.e. an obligation. Historically this idea came from the struggles of under-represented people against their oppressive governors. The corollary to this argument is that if one has an obligation, it confers a right: if one is obligated to relieve pain in an animal, then that animal has a right to live without pain and distress. It is but one tiny step from this argument to the conferring of complete equality of animal rights with those of humans.{4769} Utilitarians obviously have a problem with rights theories, because they undermine the cost-benefit analysis that is so fundamental. Developments in the 19th-21st CenturiesThe English were the first to pass a law against cruelty to animals, called Martin's Act of 1822. Others followed fairly soon; judges in New York in 1822 ruled that it was a misdemeanor under common law to abuse animals. The RSPCA was originally founded in 1824 and was chartered in 1840 by Queen Victoria. England is also the location of the first anti-research group, originally founded in 1875 by feminist Frances Cobbe, which became the British Union for the Abolition of Vivisection in 1898. In the US, the American Society for the Protection of Cruelty to Animals (ASPCA) was founded by Henry Bergh in 1866. The late 19th century also saw the emergence of a scientific view that animal rights was an anthropomorphic view, hearkening back to Descartes' opinion that animals were simply mechanistic beings with no capacity to feel pain. Pavlov wrote in 1927 that animals acted mechanically, "without any need to resort to fantastic speculations as to the existence of any possible subjective states." The Nazis passed the most comprehensive animal protection laws abolishing the use of animals in research, in 1933. There were many changes in the ban to accommodate defense plans, but the laws sound eerily similar to those of today: no research on primates, dogs, cats or horses, and the issuing of licences to institutions (rather than individuals) to conduct vivisection. There were also rules for transporting animals in cars and trains. During the war, experiments on Jews and Romani children were "validated" by repeating them in animals, because the animals were in better health than the people. After the war, animal research increased exponentially, and beginning the 1960s various movements against animal research started. The "Oxford group" was a small group of intellectuals opposed to the exploitation of animals. Ruth Harrison, Richard Ryder, Stanley and Roslind Godlovitch, and John Harris were all influential in this group. Ryder coined the term "specieism" while in the bathtub; he replaced this first with "sentientism" and now with "painism" and has a web site about it. One of their books, Animals, Men and Morals: An Inquiry into the Maltreatment of Non-humans (1971), is no longer in print (and costs quite a lot!). Peter Singer met up with the group in Oxford, wrote a review of the book, and was inspired to go on to write Animal Liberation, the "bible" of the animal liberation movement. The ALF was founded in the 1970s in England, set fire to a Hoechst lab near Milton Keynes, and is active in some 38 countries. In the US, Henry Spira coined the practice called "reintegrative shaming", whereby companies are "encouraged" to stop the use of animals. This practice was effective in coercing Revlon into stopping the Draize test and putting up the funds to found the Center for Alternatives to Animal Testing.
Maslow's hierarchy of needs has been applied to animals.{3827} 1. Physical needs Another concept is that of the "Five Freedoms", including freedom from: 1. thirst, hunger, malnutrition; One way to approach the evaluation of protocols is with a consideration of ethics and morals, a set of basic principles, a casuistry grid, and application of these to human subject research as a model. Ethics and morals are not the same thing. Morals are a person's beliefs about what is right or wrong. Ethics are an assessment tool (or a science) by which one can decide whether a given act is appropriate. In order to determine whether an act is ethical, one must possess a set of principles and the ability to apply them systematically, rather than just making a moral judgment. In human subject research, a document called the Belmont Report was produced by a committee of the National Commission for the Protection of Human Subjects in 1979. It sets forth three conditions for human subject research: (1) respect for the person; (2) justice; and (3) beneficence (kind or charitable acts). A similar committee appointed by NASA adapted this material to produce the Sundowner Report in 1995 in order to address questions about the use of rhesus macaques in space and to develop explicit principles for the ethical evaluation of animal research. It relied on the only implied principles contained in the Guide and the Animal Welfare Act (but there is no mention of the PHS policy "US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training"). The Sundowner Report restated the three basic principles relevant to animal use in research: (1) respect for life (justification of animal numbers and species, replacement with non-animal systems); (2) societal benefit (a project should consider potential good to society, populations affected, and burdens borne by the subjects); and (3) non-maleficence (minimizing pain and distress). Casuistry is the application of general principles of ethics to the determination of right and wrong. The Belmont Report contains a grid to be used for review of human research. It contains four quadrants: medical indications, quality of life, patient preferences, and contextual features. The same author presented an adapted grid to be used for animal research. This sort of system can be useful in evaluating, for example, research with transgenic animals, in which it can be a bit difficult to apply the 3R's.
Others have modified this approach; one such modification involves decision making rules and numerical values assigned to generate a quantitative result for use in evaluating whether a protocol should be approved.{4768}{4081}
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©1999, Janet Becker Rodgers, DVM, MS, DipACLAM, MRCVS All rights reserved. Comments? Send an email to janet.rodgers@vet.ox.ac.uk |
"The French have already discovered that the blackness of the skin is no reason a human being should be abandoned without redress to the caprice of a tormentor. It may one day come to be recognized that the number of the legs, the villosity of the skin, or the termination of the os sacrum are reasons equally insufficient for abandoning a sensitive being to the same fate. What else is it that should trace the insuperable line? Is it the faculty of reason or perhaps the faculty of discourse? But a full-grown horse or dog, is beyond comparison a more rational, as well as a more conversable animal, than an infant of a day or a week or even a month, old. But suppose the case were otherwise, what would it avail? the question is not, Can they reason?, nor Can they talk? but, Can they suffer?"