Understanding and evaluating veterinary clinical research

Results from investigations conducted in clinical settings contribute greatly to determining how veterinarians practice medicine. It is important for the practitioner to understand how clinical information is collected, analyzed, and communicated in journals and presentations at conferences. Clinical research is either retrospective in observational studies, looking at historical medical records as the source of data, or prospective in both experimental and observational studies, where the study is designed before any patients are included. Prospective, experimental studies provide the more reliable results, although they form a minority of published reports. Randomized, controlled trials are the most reliable format, and attempts should be made to use this design more often in veterinary medicine. Care must be taken in the conduct of clinical research to reduce sources of bias that can yield false findings, particularly in small, retrospective studies. Statistical analysis is the key to data interpretation, but must be applied appropriately to avoid either wrong assumptions or misconception. Regardless of how studies are conducted, it is important for the practitioner to be an astute reader of the clinical literature. An understanding of clinical research methods will result in better medical standard of care recommendations and practice.     

The REFLECT Statement: Reporting Guidelines for Randomized Controlled Trials in Livestock and Food Safety: Explanation and Elaboration†

Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest that similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996, with a revised edition published in 2001. The CONSORT statement consists of a 22‐item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies; the use of deliberate challenge models in some trials and the common use of non‐clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.     

Thromboembolic therapies in dogs and cats: an evidence-based approach.

In veterinary medicine, we are forced to make use of less than ideal "evidence," such as extrapolation from experimental studies in dogs and cats without naturally occurring diseases and from clinical trials in other species (particularly human clinical trials), as well as limited information gained from veterinary clinical experience, small clinical trials, case studies, and anecdotal reports. In this article, specific treatment recommendations are made for each of the common thromboembolic conditions seen in dogs and cats. These recommendations are made with the important caveat that, to date, such suggested therapeutic approaches are based on limited evidence.     

Illness Severity Scores in Veterinary Medicine: What Can We Learn?

Illness severity scores are gaining increasing popularity in veterinary medicine. This article discusses their applications in both clinical medicine and research, reviews the caveats pertaining to their use, and discusses some of the issues that arise in appropriate construction of a score. Illness severity scores can be used to decrease bias and confounding and add important contextual information to research by providing a quantitative and objective measure of patient illness. In addition, illness severity scores can be used to benchmark performance, and establish protocols for triage and therapeutic management. Many diagnosis‐specific and diagnosis‐independent veterinary scores have been developed in recent years. Although score use in veterinary research is increasing, the scores available are currently underutilized, particularly in the context of observational studies. Analysis of treatment effect while controlling for illness severity by an objective measure can improve the validity of the conclusions of observational studies. In randomized trials, illness severity scores can be used to demonstrate effective randomization, which is of particular utility when group sizes are small. The quality of veterinary scoring systems can be improved by prospective multicenter validation. The prevalence of euthanasia in companion animal medicine poses a unique challenge to scores based on a mortality outcome.     

Methodological quality and completeness of reporting in clinical trials conducted in livestock species

Randomized controlled trials (RCTs) are the gold standard for evaluating efficacy of treatments under real world conditions and, as such, it is important that they are conducted with methodological rigour to prevent biased results. Many medical journals have adopted a standard checklist for reporting of RCTs, the CONSORT statement. The objective of this study was to evaluate clinical trials in livestock populations to assess methodological quality and completeness of reporting and to investigate the association between these criteria and treatment effects. A total of 100 clinical trials published between 2006 and 2008 in the English language were randomly selected. For each trial, 2 reviewers independently completed a checklist based on the CONSORT statement and a different 2 reviewers completed a standard template describing the outcomes used and the statistical significance of all reported treatment effects. Disagreements among reviewers were resolved by consensus. The results showed that there were substantive deficiencies in the reporting of many of trial features, both related to methodological quality and completeness of reporting. Details on key features such as randomization, double blinding, and the number of subjects lost to follow-up were reported in only 67, 4, and 62% of trials, respectively. Reporting of random allocation to treatment group was associated with a lower proportion of positive treatments effects within trials, as was reporting of inclusion/exclusion criteria for study subjects, details on the intervention, animal signalment, significance tests of baseline differences for at least one variable, and the methods used to measure all outcomes. The results suggest that there are deficiencies in the current reporting of important features of RCTs conducted in livestock species and that these deficiencies may be associated with biased treatment effects. The creation and adoption of standards for trial reporting in livestock could aid authors, reviewers, and editors in ensuring that necessary trial details are reported in all published trials.     

Effective use of simulations for the teaching and acquisition of veterinary professional and clinical skills

Simulation technology will feature prominently in this exciting, yet challenging, time for veterinary medicine. The profession is evolving to keep pace with rapid changes in clinical practice, scientific discovery, and educational strategy, while ensuring that it follows the public mandate to produce competent veterinarians. Among the challenges to meeting this educational goal are limitations-due to important issues such as animal welfare-on the availability of real patients for training. Drawing chiefly on the experience in human medicine, this article explores the use of simulations in veterinary medical education to provide safe and ethical alternative opportunities for learners to practice essential clinical and professional skills.     

Veterinary Randomized Clinical Trial Reporting: A Review of the Small Animal Literature

The randomized clinical trial (RCT) is a valuable research method for the evaluation of new treatment and prevention regimens in veterinary medicine. Reporting of clinical trials in other disciplines has not been complete. Without complete information on the conduct and results of a clinical trial, readers cannot optimize their use of the information presented. This report represents an objective review of randomized clinical trials in the veterinary small animal literature from 1986 to 1990. Results indicate that RCT reports in the small animal veterinary literature are incomplete. The importance of reporting on particular aspects of RCT research is described.     

Issues of reporting in observational studies in veterinary medicine

Observational studies are common in veterinary medicine; the results may be used to inform decision-making, future research, or as inputs to systematic reviews or risk assessment. To be of use, the results must be published, all of the outcomes that were assessed must be included in the publication, and the research (methods and results) must be reported in sufficient detail that the reader can evaluate the internal and external validity. In human healthcare, concerns about the completeness of reporting – and evidence that poor reporting is associated with study results – have led to the creation of reporting guidelines; these include the STROBE statement for observational studies.     

New perspectives in cardiovascular medicine: the calcium channel blocking drugs

Calcium channel blocking drugs reduce the influx of calcium (Ca++) through cell membrane passageways in excitable tissues. This unique pharmacodynamic action represents an important new addition to cardiovascular therapeutics. Clinically available members of this diverse group of compounds are verapamil, nifedipine, and diltiazem. Beneficial responses to these drugs can be explained by vasodilatation and resulting hemodynamic improvement in tissue perfusion-oxygen demand relationships, by suppression of Ca++-dependent arrhythmogenic mechanisms, by direct reduction of pathologic Ca++ overload in ischemic injured cells, or by a combination of these effects. Calcium channel blockade already has become a therapeutic mainstay in human medicine for management of ischemic heart disease and some forms of cardiac dysrhythmias. Relative to veterinary medicine, Ca++ channel blocking drugs may provide a clinical option for controlling supraventricular tachyarrhythmias. Other indications might include obstructive cardiomyopathies, shock-trauma, and congestive heart failure. Importantly, however, essential issues about adverse cardiovascular side effects of Ca++ channel blocking drugs remain unresolved and controversial. Recent studies especially have raised questions about the tendency for Ca++ channel blockade to exacerbate preexisting or occult myocardial contractile failure. Such pharmacodynamic complexities should be assessed judiciously as the Ca++ channel blocking drugs are appraised for entry into veterinary internal medicine.     

《兽医内科学》系统性课程思政教学的探索与实践

兽医内科学是动物医学专业的主干课程,是动物临床医学的支柱课程,在全面实施课程思政的大背景下,系统分析兽医内科学的课程地位、实施课程思政的必要性、面临的困境及原因、实施路径等问题,创造性地将思想政治教育和兽医内科学教学有机融合,可以充分发挥兽医内科学课程的育人功能,从而实现以专业课程为依托培养新时代高水平、高素质兽医人才的目标。     

Evidence‐Based Medicine: The Design and Interpretation of Noninferiority Clinical Trials in Veterinary Medicine

Noninferiority trials are clinical studies designed to demonstrate that an investigational drug is at least as effective as an established treatment within a predetermined margin. They are conducted, in part, because of ethical concerns of administering a placebo to veterinary patients when an established effective treatment exists. The use of noninferiority trial designs has become more common in veterinary medicine with the increasing number of established veterinary therapeutics and the desire to eliminate potential pain or distress in a placebo‐controlled study. Selecting the appropriate active control and an a priori noninferiority margin between the investigational and active control drug are unique and critical design factors for noninferiority studies. Without reliable historical knowledge of the disease response in the absence of treatment and of the response to the selected active control drug, proper design and interpretation of a noninferiority trial is not possible. Despite the appeal of conducting noninferiority trials to eliminate ethical concerns of placebo‐controlled studies, there are real limitations and possible ethical conundrums associated with noninferiority trials. The consequences of incorrect study conclusions because of poor noninferiority trial design need careful attention. Alternative trial designs to typical noninferiority studies exist, but these too have limitations and must also be carefully considered.     

New drugs in veterinary dermatology.

This article discusses several different new drugs currently being used in dermatology. Most of the drugs discussed showed some promise as being a useful therapy in veterinary medicine, but a few have questionable efficacy (nonsedating antihistamines). The majority of these drugs have not had any pharmacokinetic or clinical trials conducted on them in small animals. Hopefully, in the future, more studies are funded so that we can determine the clinical therapeutical efficacy and appropriate doses for these drugs.     

The REFLECT Statement: Methods and Processes of Creating Reporting Guidelines for Randomized Controlled Trials for Livestock and Food Safety by Modifying the CONSORT Statement†

The conduct of randomized controlled trials in livestock with production, health and food‐safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2‐day consensus meeting was held on 18–19 November 2008 in Chicago, IL, USA, to achieve the objective. Prior to the meeting, a Web‐based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food‐safety researchers, livestock‐production specialists, journal editors, assistant editors and associate editors. Prior to the meeting, the attendees completed a Web‐based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22‐item checklist. Fourteen items were modified from the CONSORT checklist and an additional sub‐item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health and food‐safety outcomes.     

The role of albumin replacement in the critically ill veterinary patient

Objective: To review the human and veterinary literature on the physiological role and effects of therapeutic albumin supplementation. Data sources: Data from human and veterinary literature was reviewed. Human data synthesis: Hypoalbuminemia often occurs in a variety of critical illnesses, and contributes to the development of life‐threatening complications, including pulmonary edema, delayed wound healing, feeding intolerance, hypercoaguability, and multiple organ dysfunction. Serum albumin concentration has been used as a prognostic indicator in cases of chronic hypoalbuminemia. The use of albumin replacement therapy in humans is sometimes controversial, but may be associated with improved morbidity and decreased mortality. Veterinary data synthesis: Unlike human literature, there is a paucity of controlled clinical studies in the literature regarding albumin supplementation in veterinary patients. Rather, the majority of published studies were performed in experimental animals or via retrospective analyses. One recent study evaluated the use of plasma to improve albumin concentration in dogs with hypoalbuminemia. Other older studies investigated wound healing in dogs with experimentally induced hypoalbuminemia. As in human medicine, serum albumin concentration may be helpful as a prognostic indicator in critically ill dogs. Conclusion: Albumin is one of the most important proteins in the body because of its role in maintenance of colloid oncotic pressure, substrate transport, buffering capacity, as a mediator of coagulation and wound healing, and free‐radical scavenging. Albumin replacement in veterinary medicine is difficult, but until prospective clinical trials determine the efficacy of albumin replacement are conducted, a suggested clinical guideline would be to maintain albumin concentration at or above 2.0 g/dl utilizing fresh frozen plasma.     

The REFLECT Statement: Methods and Processes of Creating Reporting Guidelines for Randomized Controlled Trials for Livestock and Food Safety

The conduct of randomized controlled trials in livestock with production, health, and food-safety outcomes presents unique challenges that might not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2-day consensus meeting was held on November 18–19, 2008 in Chicago, IL, to achieve the objective. Before the meeting, a Web-based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food-safety researchers, livestock production specialists, journal editors, assistant editors, and associate editors. Before the meeting, the attendees completed a Web-based survey indicating which CONSORT statement items would need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22-item checklist. Fourteen items were modified from the CONSORT checklist, and an additional subitem was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health, and food-safety outcomes.     

Food-supply veterinary medicine and veterinary medical education: an Australian perspective

Food-supply veterinary medicine has been an essential part of veterinary degree programs in Australia since the first veterinary school opened in the late nineteenth century. Australian veterinary schools, like others internationally, are being challenged by the relevance of material in current curricula for modern food-supply veterinary medicine. Additionally, student aspirations are a major issue, as curriculum designers balance companion-animal training with the herd/flock-based issues that focus on productivity and profitability. One of the challenges is to examine the relative balance of education in generic skills (self-knowledge, change management, teamwork, leadership, negotiation) with more technically or scientifically based education. An ongoing process of curriculum review and renewal, which involves input from both external and internal stakeholders and allows regular review and assessment, is needed to ensure continuing curriculum relevance.     

Myasthenia gravis in dogs with an emphasis on treatment and critical care management

Objective – To review the human and veterinary literature on the pathophysiology of myasthenia gravis (MG) and describe treatment options for clinical use in people and animals. Data Sources – Human and veterinary clinical reports, studies and reviews, textbooks, and recent research findings in MG from 1996 present, with a focus on treatment and patient management. Human Data Synthesis – MG is a well‐described condition in people with new research and treatment options available. Many of the newest therapeutic options available in veterinary medicine for MG are based on current strategies used in people with this condition. Seronegative MG is well described in people and provides insight to clinical cases encountered in veterinary medicine when the index of suspicion is high though serologic tests are negative. Veterinary Data Synthesis – Previous studies in veterinary medicine focused on the use of acetylcholinesterase inhibitors as the main form of treatment in canine MG. Recent studies, mainly case series and case reports, emphasize the use of immunomodulatory treatments as an alternative for long‐term treatment. However, there are no randomized, controlled studies on treatment with immunomodulatory therapy for MG in dogs available to assess the efficacy of this treatment strategy. Conclusions – Although early recognition of clinical signs is most important in the outcome of patients with MG, further understanding the pathophysiology of MG may lead to earlier diagnosis and novel treatment strategies. The discovery of additional autoantibodies against striated muscle proteins in dogs, should enhance our understanding of diseases affecting the neuromuscular junction. In addition, clinical data for canine MG could be applied to other autoimmune disorders.     

Trends in veterinary clinical and fundamental pharmacology: past and future in The Netherlands

Veterinary pharmacology has undergone a gradual development in the Netherlands during this century. Starting from a historical perspective the paper aims to provide an overview of future trends and important issues in the area of veterinary pharmacology and toxicology. It is pointed out that this discipline comprises several subdisciplines as the comparative aspect of both, pharmacology and toxicology, is inherent to veterinary medicine which has to address a broad variety of animal species. Thus, the comparison of drug effects, side effects, and drug disposition as well as the comparison of the species-specific susceptibility to xenobiotics are obvious challenges in this discipline. Several areas in clinical pharmacology are highlighted to indicate future research needs. Finally, the principles of Good Veterinary Practice are presented as the 'golden standard' in veterinary clinical pharmacology.