World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of ectoparasiticides against myiasis causing parasites on ruminants

These guidelines have been prepared to assist in the planning, conduct and interpretation of studies for the assessment of efficacy of ectoparasiticides against the myiasis causing parasites of ruminants. These guidelines specifically focus on larvicidal efficacy against myiasis causing flies. Information is provided on the selection of animals, dose determination and dose confirmation studies, field studies, record keeping and result interpretation. These guidelines advocate the use of pen facilities for dose determination and dose confirmation studies for defining therapeutic and persistent efficacy. These guidelines are also intended to assist investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new ectoparasiticides, and to facilitate the world-wide adoption of standard procedures.     

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of ectoparasiticides against biting lice, sucking lice and sheep keds on ruminants

These guidelines have been prepared to assist in the design, implementation and interpretation of studies for the assessment of the efficacy of ectoparasiticides against biting and sucking lice and sheep keds on ruminants. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping and result interpretation. These guidelines advocate the use of pen facilities for dose determination and dose confirmation studies for defining therapeutic and persistent efficacy. These guidelines are also intended to assist investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision making process, to assist in the approval and registration of new ectoparasiticides, and to facilitate the world-wide adoption of standard procedures.     

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of acaricides against (mange and itch) mites on ruminants

These guidelines have been prepared to assist in the planning, conduct and interpretation of studies for the assessment of the efficacy of acaricides against mange and itch mites on ruminants. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping and result interpretation. These guidelines also are intended to assist the investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new ectoparasiticides, and to facilitate the worldwide adoption of standard procedures.     

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of acaricides against ticks (Ixodidae) on ruminants

These guidelines have been prepared to assist in the planning, conduct and interpretation of studies for the assessment of the efficacy of acaricides (excluding vaccines and other bio-control agents) against single and multi-host ticks (Ixodidae) on ruminants. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping and result interpretation. The use of pen facilities is advocated for dose determination and confirmation studies for defining therapeutic and persistent efficacy. A minimum of two studies per tick species for which claims are sought is recommended for each dose determination and dose confirmation investigation. If dose confirmation studies demonstrate greater than 95% efficacy the sponsor may proceed to field studies, where a minimum of two studies per geographical location is preferred to confirm the therapeutic and persistent efficacy under field conditions. If dose confirmation studies demonstrate less than 95% efficacy then longer-term field studies can be conducted over two tick seasons with a minimum of two studies per geographical location. These studies can incorporate other control methods such as tick vaccines, to demonstrate stable long-term tick management. Specific advice is also given on conducting studies with paralysis ticks. These guidelines are also intended to assist investigators on how to conduct specific experiments, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new acaricides, and to facilitate the worldwide adoption of standard procedures.     

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestation on dogs and cats

These guidelines are intended to assist the planning and conduct of laboratory and clinical studies to assess the efficacy of ectoparasiticides applied to dogs or cats for the purpose of treating, preventing and controlling flea and tick infestations. The term ectoparasiticide includes insecticidal and acaricidal compounds, as well as insect growth regulators. The range of biological activities accruing from animal treatment that are considered include: repellency and anti-feeding effects, knockdown, speed of kill, immediate and persistent lethal effects, and interference with egg fertility and subsequent development of off-host life cycle stages. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping, interpretation of results and animal welfare. These guidelines are also intended to assist registration authorities involved in the approval and registration of new parasiticides, and to facilitate the worldwide adoption of harmonized procedures.     

World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of anticoccidial drugs in chickens and turkeys

These guidelines have been written to aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against Eimeria species in chickens and turkeys. The information provided deals with many aspects of how to conduct controlled studies in battery cages (dose determination), floor pens (dose confirmation), and commercial facilities (field effectiveness studies), the selection of birds, housing, feeding, preparation of medicated rations, record keeping, diagnostic techniques, and methods for the preparation, maintenance and use of parasites. These guidelines are also intended to assist investigators in conducting specific studies, provide specific information for registration authorities involved in the decision-making process, assist in the approval and registration of new anticoccidial drugs, and facilitate the world-wide adoption of standard procedures.     

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of equine anthelmintics

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp, which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.     

World association for the advancement of veterinary parasitology (WAAVP): second edition of guidelines for evaluating the efficacy of equine anthelmintics.

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp., which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.     

World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the effectiveness of anthelmintics in chickens and turkeys

These guidelines have been prepared to assist in the planning, operation and interpretation of studies designed to assess the effectiveness of drugs against helminth parasites of chickens and turkeys. They are the first to be compiled under the auspices of the World Association for the Advancement of Veterinary Parasitology (WAAVP) for these parasites. The advantages and disadvantages of the widely used critical and controlled tests are discussed. Information is provided on the selection of animals for experiments, animal housing, feed, dose determination studies, confirmatory and field trials, record keeping and necropsy procedures. This document should help investigators and those involved in product approval and registration in conducting and evaluating studies concerned with determining the effectiveness and safety of anthelmintic drugs.     

Statistical principles of "good clinical practice" in veterinary medicine--a position paper for planning, implementation and evaluation of empirical studies

The complexity of the design, conduct, analysis and evaluation of empirical studies necessitates a high degree of interdisciplinary collaboration in all areas of research. In order to make sure that no essential harmonisation is missed among the plenitude of processes, it has become common to provide direction on the essential operating procedures in so called "Good ... Practice" guidelines in recent years. In pharmaceutical research on human medicinal products guidelines on Good Clinical Practice have been an integral part of research and development in industry, academia, and the regulatory authorities for a long time. On the other hand, in the development and registration of pharmaceuticals for veterinary use such procedures are not yet established to this extent in Germany. Notwithstanding there being a lot of regulations on specialised subjects. This paper tries to summarise the current state of the discussion and to give an overview on the important points in the design, conduct, analysis and reporting of veterinary clinical studies mainly from an biometrical point of view.     

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) Guidelines for evaluating the efficacy of anthelmintics in swine

As a follow-up to a previous guideline publication on efficacy evaluation of anthelmintics in ruminants, an expert group of the World Association for the Advancement Veterinary Parasitology presents similar guidelines for the testing of anthelmintics in swine. The goal of the guidelines is to develop uniform testing standards and registration requirements. Data obtained from investigations according to the guidelines should be internationally accepted in the registering of drugs. Further, the use of the guideline may contribute towards reducing costs, labor and the number of experimental animals used for durg testing.     

Valid methods: the quality assurance of test method development, validation, approval, and transfer for veterinary testing laboratories.

Third-party accreditation is a valuable tool to demonstrate a laboratory's competence to conduct testing. Accreditation, internationally and in the United States, has been discussed previously. However, accreditation is only I part of establishing data credibility. A validated test method is the first component of a valid measurement system. Validation is defined as confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled. The international and national standard ISO/IEC 17025 recognizes the importance of validated methods and requires that laboratory-developed methods or methods adopted by the laboratory be appropriate for the intended use. Validated methods are therefore required and their use agreed to by the client (i.e., end users of the test results such as veterinarians, animal health programs, and owners). ISO/IEC 17025 also requires that the introduction of methods developed by the laboratory for its own use be a planned activity conducted by qualified personnel with adequate resources. This article discusses considerations and recommendations for the conduct of veterinary diagnostic test method development, validation, evaluation, approval, and transfer to the user laboratory in the ISO/IEC 17025 environment. These recommendations are based on those of nationally and internationally accepted standards and guidelines, as well as those of reputable and experienced technical bodies. They are also based on the author's experience in the evaluation of method development and transfer projects, validation data, and the implementation of quality management systems in the area of method development.     

Linking causal concepts, study design, analysis and inference in support of one epidemiology for population health

In this paper, which is dedicated to Dr. Calvin Schwabe, I review the concepts of causation and how they impact on study design, analysis and interpretation of results. Notwithstanding the fact that no observational study can prove causation, there are a number of issues that if addressed sufficiently, can improve the validity and usefulness of our studies. These are elaborated with specific recommendations for the conduct of future observational research. Approaches that have been useful in my teaching and research experience are also described.     

International harmonisation of anthelmintic efficacy guidelines (Part 2).

The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of this second paper is to present additional guidelines established by the Working Group on anthelmintic guidelines: (1) efficacy of anthelmintics: specific recommendations for equine (VICH GL15), (2) efficacy of anthelmintics: specific recommendations for porcine (VICH GL16), (3) efficacy of anthelmintics: specific recommendations for canine (VICH GL19), (4) efficacy of anthelmintics: specific recommendations for feline (VICH GL20) and (5) efficacy of anthelmintics: specific recommendations for poultry (VICH GL21). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.     

Potential environmental consequences of administration of ectoparasiticides to sheep

Sheep ectoparasiticides, which include the synthetic pyrethroids, the organophosphates, the 'insect'-growth regulators, the formamidines and the spinocyns, enter into the environment primarily through disposal of dip or fleece scours, as well as with contaminated faeces and urine. Due to the large quantities of spent dip, risks associated with environmental contamination are high. Synthetic pyrethroids and organophosphates pose risks to dung, soil and aquatic fauna; concerns over potential ecotoxicity to vertebrates and invertebrates have resulted in the cessation of their use in many countries. There is very little information regarding the ecotoxicity of 'insect'-growth regulators, formamidines or spinocyns, with no studies focussing on sheep. Here, the impact of sheep ectoparasiticides is discussed in terms of their potential to enter into the environment, their toxicity and their impact on ecosystem functioning. Where there are no data for excretion or toxicity of the ectoparasiticides used in sheep production, examples to demonstrate potential impacts are taken from laboratory ecotoxicity tests and the cattle literature, as well on work with foliar insecticides. Future research priorities are suggested to allow assessment of the environmental consequences of sheep ectoparasiticide treatments, which are essential for future sustainable sheep production.     

Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine

In veterinary drug development procedures, pharmacokinetic (PK) and pharmacodynamic (PD) data have generally been established in separate, parallel studies to assist in the design of dosage schedules for subsequent evaluation in clinical trials. This review introduces the concept of PK/PD modelling, an approach in which PK and PD data are generated in the same study, and used to derive numerical values for PD parameters based on drug plasma concentrations. The PD parameters define the efficacy, potency and slope (sensitivity) of the concentration-effect relationship. It is proposed that the parameters derived from PK/PD modelling may be used as an alternative and preferred approach to dose titration studies for selecting rational dosage regimens (both dose and dosing interval) for further evaluation in clinical trials. In PK/PD modelling, the explicative variable for effect is the plasma concentration profile. The PK/PD approach provides several advantages over dose-titration studies, including determination of a projected dosage regimen by investigation of a single dose, in contrast to dose-ranging studies which by definition require testing of multiple dosage. Implementation of PK/PD modelling in the veterinary drug development process is currently constrained by the limited number of veterinary studies performed to date, and the consequently limited understanding of PK/PD concepts and their absence from regulatory authority guidelines. Nevertheless, PK/PD modelling has major potential for rational dosage regimen determination, as it considers and quantifies the two main sources of interspecies variability (PK and PD). It is therefore applicable to interspecies extrapolation and to multiple species drug development. As well as the currently limited appreciation of PK/PD principles in the veterinary scientific community, a further constraint in implementing PK/PD modelling is the need to validate PK/PD approaches and thereby gain confidence in its value by pharmaceutical companies and regulatory authorities.     

World association for the advancement of veterinary parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine and ovine)

During the 8th International Conference of the World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) held in Sydney, Australia, in 1977, President S. Gaafar appointed a committee to prepare international guidelines for evaluating the efficacy of anthelmintic products. The goal was to develop uniform testing standards and registration requirements to expedite the testing and approval of effective products with a minimum of labor, money, and experimental animals without sacrificing scientific validity. Achievement of such a goal would mean that data from investigators in one country could be used in registering drugs in another country.

These guidelines, which were approved by the membership at the general meeting of the 9th International Conference of the W.A.A.V.P. on July 16, 1981 in Budapest, Hungary, are only a beginning in the development of uniform international methods for testing the efficacy of anthelmintics. We now propose that they be used by the scientific community recognizing that, at this time, these guidelines have not been officially reviewed or accepted by any government regulatory authority. Investigators are encouraged to evaluate this document critically and to recommend modifications promptly to the Committee so that they may be incorporated in these guidelines before the 10th International Conference to be held in Perth, Australia in 1983.     

抗动物外寄生虫药物的研究进展

使用化学杀虫剂仍然是防治动物外寄生虫病的主要手段,其中大多数杀虫剂作用于节肢动物神经系统,而昆虫生长调节剂可阻碍或干扰昆虫生长和发育。本文对现阶段国内外使用的外寄生虫杀虫剂的种类和特点、各种杀虫剂的作用机制以及杀虫剂的使用等方面的研究进展进行了综述。     

International harmonisation of anthelmintic efficacy guidelines

The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan, and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of the present paper is to present the guidelines established by the working group on Anthelmintic Efficacy Guidelines: (1) efficacy of anthelmintics: general requirements (VICH GL7); (2) efficacy of anthelmintics: specific recommendations for bovines (VICH GL12); (3) efficacy of anthelmintics: specific recommendations for ovines (VICH GL13); (4) efficacy of anthelmintics: specific recommendations for caprines (VICH GL14). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.     

卡洛芬注射液辅助治疗牛细菌性呼吸疾病的疗效研究

为评价卡洛芬注射液与泰拉霉素注射液联用治疗牛呼吸道疾病（bovine respiratory disease,BRD）的效果,并确定合理的给药剂量,试验选择64头患呼吸道疾病的牛,随机分为A、B两组,每组32头,其中A组皮下注射给予泰拉霉素注射液（推荐剂量2.5 mg/kgbw）,同时肌内注射给予卡洛芬注射液（II期临床试验确认剂量1.4 mg/kgbw）;B组只皮下注射给予泰拉霉素注射液（推荐剂量2.5 mg/kgbw）。所有试验牛各种药均只给予1次。试验期间观察记录各组牛的临床症状,并对其进行评分;通过对各试验牛的炎症因子、致病菌、特定病原抗原/抗体的检测,评价卡洛芬注射液对牛呼吸道疾病的辅助治疗效果。试验结果显示,相比于单独使用泰拉霉素注射液,卡洛芬注射液与泰拉霉素注射液联用治疗BRD可以在更短时间内消除牛体内病原菌感染带来的炎症反应;泰拉霉素注射液单独使用或与卡洛芬注射液联用治疗BRD,给药3 d病牛的血清PCT浓度均明显下降（P＜0.05）,但两药联用的下降速度更加显著（P＜0.05）。结果表明,临床上推荐卡洛芬注射液与泰拉霉素注射液联用,皮下注射,一次量为1.4 mg/kgbw,可有效辅助治疗牛呼吸道疾病