Ethical, scientific and practical standards in clinical practice research

Authors


Equine welfare and veterinary medicine need field research by competent veterinarians. Animal welfare considerations need to meet the highest standards to promote the value of field research results and to allow us to meet the public and professional expectations of animal welfare and patient care. In common with other veterinary journals, EVJ insists that authors assure that ethical and legal requirements have been met at the time of manuscript submission [1], and practitioners planning to undertake a research study should ensure that they are aware of the details of such requirements. These are recommendations and guidelines that make sense.

The need for clinical practice-sourced research

New areas of surgical, medical and diagnostic techniques were opened between the 1960s and the 1990s that directly and massively impacted equine care and welfare. These advances included, but are not limited to, flexible endoscopy, ultrasonography, parasiticides, rational antimicrobial use, vaccinology, and abdominal, respiratory and orthopaedic surgery, to name but a few. All have clearly had large impact. Now, university-originating but practice-altering changes come at a slower pace, as capital resources tighten, case-loads dwindle, the focus is more molecular, and new diagnostic technologies for humans move beyond the economic reach of most equine hospitals. Even now, if university research impacts horses it is often as a side benefit from nonequine research, focused on commercial value directly to the university and/or to another commercial venture (i.e. veterinary pharmaceutical industry). This is especially true as industry uses more economical university resource contracts to fund their commercial ventures. There is little doubt that there will be continued vaccine, pharmaceutical, molecular, immunological and diagnostic advances originating in universities. However, important and impactful clinically relevant research requires competent clinical practitioners with cases as subjects. Clinical practice is the most promising source of clinically relevant information in the future.

University-based clinical faculty have scripted their own case-load demise by their efficiency at dissemination of information and expertise in the form of residents to the field. That knowledge, equipment, skill and expertise was the foundation of the veterinary teaching hospital case-load. The reduction of case-load to tertiary care has increased institutional bias in veterinary teaching hospital case material and questions relevance and population inferential capacity of studies of clinically important issues where the case material is derived solely from the university teaching hospital. It is hard to remember when a flexible endoscopic airway examination or a tendon ultrasound was a case to be referred. Yet, there is hope for continued major advances if clinical practitioners and university faculty members join together in the effort to produce clinically relevant research for the future. And clearly, there are already many examples of this collaboration; for example, one of the largest studies yet performed in equine therapeutics was conducted by exactly this sort of multicentre collaboration [2, 3], and combining outcome data from multiple centres has provided the necessary evidence that allows perinatologists to use admission lactate concentrations to provide advice to their clients on likely outcomes [5].

Animal use in research is a privilege, not a right

Using animals as research subjects is clearly a privilege. Great care should be taken so that the use of an animal in research has the greatest impact on the well-being of animals and human beings as a whole. Additionally, it is essential that the support of animal welfare is a central aim of our profession, as evidenced by many veterinary oaths from different countries:

  • Republic of Ireland: ‘I solemnly and sincerely declare…I will promote the welfare of animals entrusted to my care’ (http://www.vci.ie).
  • Royal College Veterinary Surgeons, UK: ‘I promise above all that I will pursue the work of my profession with uprightness of conduct and that my constant endeavour will be to ensure the welfare of animals’ (http://www.rcvs.org.uk/home).
  • Federazione Nazionale Ordini Veterinari Italiani: ‘I do solemnly promise to dedicate my skills and my ability to protect…animal welfare, promoting respect as sentient beings, to commit myself in my continual improvement, updating my knowledge on evolving science; to carry out my activities … according to science …’ (http://www.fnovi.it). This is the most laudable of the oaths, in my opinion.
  • American Veterinary Medical Association: ‘I solemnly swear to use my scientific knowledge and skills for the benefit of society through the protection of animal health and welfare, the prevention and relief of animal suffering, the conservation of animal resources, the promotion of public health, and the advancement of medical knowledge’ (https://www.avma.org).

These declarations and oaths require veterinary practitioners, specialist and generalist alike, to contribute to the knowledge base of equine care not only with life-long learning, but also with an obligation to contribute to knowledge and to protect animal welfare. It is accepted that professionalism requires life-long learning. I, and these oaths and declarations, argue one step further. Expansion of knowledge through controlled research and dissemination of that information to the veterinary community is a hallmark of professionalism. This will continue to require humane and careful animal use that clearly contributes, and is essential, to research conclusions.

Collaboration: the reasonable step

Clinicians embarking on a research study must make ethical use of animals in research their first priority. It is often a good plan for the practitioner planning to embark on clinical field research to develop collaborative relationships with researchers at universities or other institutes. Researchers based in universities and institutes can provide external assessment on research design, provide access to statistical support and provide sources of funding, diagnostic expertise and laboratory assessment. From the other direction, these researchers may be able to find additional field collaborators to support the impact of an individual idea. Do not confine yourself to the local university. The digital age allows us to collaborate with individuals across the world. With regard to animal care and use, collaborators in institutions can be a resource to an animal care and use committee or research ethics committee that can provide an external assessment of animal use and welfare considerations. Equine Veterinary Journal strongly urges practitioners to have their research proposals assessed by such committees if at all possible and, indeed, our author guidelines specify this requirement [1]. Retrospective studies based on case records do not require ethical permissions, but for all prospective research, whether from institutes or private practice, a clear statement of the ethical review processes and permissions pertaining to the study will be required at the time of submission of a manuscript. Equine Veterinary Journal's editors understand that in some countries such committees do not extend their services to private practice or may have differing specific requirements and are prepared to consider submissions on a case-by-case basis. Nevertheless, in compliance with a consensus statement developed by the International Association of Veterinary Medical Editors in 2010 [5], for manuscripts describing prospective research conducted with client-owned animals, owner informed consent is considered by EVJ to be mandatory.

Owner consent

Ethically, morally and professionally, if a case is included in a study where care has been altered for evaluation, the client must be aware and provide consent. This includes control and experimental cases. This is common sense and essential, not only ethically, but for the protection of the practice. If the data are to be published and disseminated, clients will know in the digital age. The clients need to be apprised of the suspected risk. You want them to invest their charge to your research. You must ask permission. A summary of the animal use protocol and the study protocol should be available to the owner. The consent form should identify the risks and, importantly, it must be made very clear to the owner that their animal's care will not be disadvantaged in any way, should they decline to join the study. There are many online resources that can give you guidance on development of this document. In general, the document should include the following:

  • The name of your practice and contact information.
  • Title of the study.
  • Study purpose and benefits to the individual and the population of horses.
  • Detailed description of procedures performed on cases.
  • Risk–benefit assessment of assignation to different study group treatments, including control and established treatments.
  • Compensation for participating in the study, if any.
  • Indication of compensation in case of problems resulting from study inclusion.
  • Costs that will be incurred by the client.
  • Information that participation is voluntary and that they may withdraw at any time.
  • Contact information if there are problems.
  • Lines for investigator and client signatures and dates.

The animal care and use committee contribution: a new vision

Animal care and use committees have moved to a commendable holistic approach. The approach to humane clinical research in the past was focused on methods of euthanasia, housing, pain management and little else. Now these committees have extended their considerations to the relevancy and adequacy of the use of animals and control issues relevant to the protocol and how the data will contribute to the literature. In addition, they seek assurances that information gleaned from the work has a net positive impact value with respect to the risk of some patients to discomfort and/or a less than desirable outcome.

This is not a bureaucratic hurdle. This is external assessment and should be welcomed in any endeavour (http://www.ama-assn.org/resources/doc/council-on-med-ed/itme-final.pdf). It is clear that self-assessment is flawed and nonreparable and comes with high risk for failure. External assessment should be sought in any endeavour. These same principles should be addressed in all clinical field research. Individuals based in practice, dependent on the jurisdiction, may not be obliged to seek approval of an animal care and use committee or similar review body. Nevertheless, the moral obligations of achieving the standards expected by such committees are universal, and the aspiring researcher, in practice, is well advised to seek formal to informal input from such a committee if possible.

Protocol review

I advise the external assessment of every protocol at the planning stage. My United States Food and Drug Administration experience brought me to this clear and relevant conclusion. I appreciated the exposure to the best minds in industry and clinical field research. We learned from each other, established reasonable goals and designed research of which I am proud to have been a part. In most cases, this was not adding burden to studies, but in fact simplifying them to achieve the common goal. Good positive external protocol assessment should lead to improvement and relevancy of the data collected. Seek individuals who can be engaged in a collaborative manner. Individuals who respond with obstructions should be avoided. Any good idea can be put to a relevant test.

The Royal College of Veterinary Surgeons (RCVS) and British Veterinary Association (BVA) have recently produced a report addressing Ethical Review for Practice-based research [6]. The distinction between clinical practice and clinical research is discussed. Ethical review of clinical research is strongly endorsed and various options for accessing ethical review of research proposals within the UK are presented. This is a useful resource, not only for veterinary clinicians working in the UK to whom the report is specifically addressed, but also for practice-based clinical researchers under the governance of other veterinary authorities. Research-orientated clinicians everywhere should consider the underlying principles that are advocated in the RCVS-BVA report as they set a benchmark for ethical practice-based clinical research.

Control subjects and masking

Adequate contemporaneous controls must be available for clinical research in either retrospective or control studies. Poor control selection can be fatal for a study. Control animals in clinical field work should be managed to the highest standard of care, especially when that care is the focus of research. Placebo studies are often inappropriate in the clinical setting. It can also be very difficult to achieve masking. Nevertheless, in most circumstances, the clinical evaluator of a subjective measure must be masked to treatment, including pain management. Outside collaboration can be useful, and masked evaluation of digital media (video, images, audio, etc) can produce objective assessments not biased to the conclusions.

Management of pain and discomfort and protocol-associated disease

Animal discomfort must be minimised. Often, a careful balance needs to be struck between pain management and the data sought. The means to address pain need to be identified within a specific protocol and carefully documented. If studies occur where pain is less than completely controlled, then a clear rationale needs to be presented and should meet collaborative external review.

A plan for protocol-associated morbidity needs to be in place. This also includes subject escape criteria that determine when a subject needs to be removed from the study so as to apply other, nonprotocol treatments or management.

Literature review

The ethical researcher must ensure that the study design and data collected will contribute to the available literature. This not only means testing new ideas, but also retesting old conclusions in new ways. In terms of animal use, one needs to provide clear literature-based information that identifies that the contributions of animals are needed and that their use will contribute to the common good. This does not mean that studies cannot be repeated, but one should be clear why the conclusions of the original study need to be retested.

Summary

  • Research in practice is essential to provide inference to the population of horses as a whole.
  • Animal use for research is a privilege, and animal welfare is the highest priority.
  • We are by oath, declaration and professionalism required to be life-long-learners, not only to learn new techniques, but also to contribute to the body of knowledge in veterinary medicine.
  • Collaboration is an important asset to animal use and study impact.
  • Owners need to know that their horses are subjects in a study.

Editors note

Extract from EVJ's Author Guidelines:

2.3. Use of animals in research

Manuscripts will be considered for publication only if the work detailed therein:

  • Follows international, national, and/or institutional guidelines for humane animal treatment and complies with relevant legislation in the country in which the study was conducted;
  • For studies using client-owned animals, demonstrates a high standard (best practice) of veterinary care and involves informed client consent;
  • Has been approved by the ethics review committee at the institution, hospital or practice at which the studies were conducted where such a committee exists;
  • Where such a committee does not exist, authors are expected to have conducted their research in a manner likely to be approved by ethics committees in most countries.

Submissions must be accompanied by a statement, in our submission form, certifying that legal and ethical requirements have been met with regards to the humane treatment of animals described in the study and specifying the ethical review committee that has overseen this process and/or the international, national and/or institutional guidelines followed. This information will be included in the Declarations Section. Please also include this information under the separate heading of ‘Ethical Considerations’ in the ‘Title page’ document (see Section 4.2).

When research animals are used, the methods section must clearly indicate that adequate measures were taken to monitor and address the welfare of the animals involved. Editors reserve the right to reject papers if there is doubt as to whether appropriate procedures have been used and also to insist that information is provided in the text as to the measures taken to protect the welfare of subjects and the outcome of procedures undertaken in respect to any pain or suffering caused.

Ancillary