Leading Off: How we can contribute to clinical research

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Sep 01, 2008


Dawn Merton Boothe
Clinical trials constitute the cornerstone of evidence-based medicine. They are a part of a broader realm of clinical research, which determines the safety and efficacy of diagnostic or therapeutic interventions and examines their impact on at-risk patient populations. Most commonly, clinical trials compare therapeutic interventions between at least two sample populations. Other examples of clinical research include observational studies (e.g. case reports; case series; and epidemiologic studies, such as adverse event reporting) and field trials (large clinical trials).

Although normal animals can be evaluated in clinical trials, patients with or at risk to develop spontaneous disease comprise the optimal study population. As such, clinical trials are more appropriately implemented in collaboration with clinicians who have a vested interest in their patients' welfare, even if the animals evaluated provide an experimental model of the disease of interest.

However, clinical research struggles for acceptance in veterinary academic and private practice environments. Yet, we can improve this vital part of veterinary medicine in several ways.

CLINICAL TRIAL CHALLENGES

Academic commitment lacking

Academia is uniquely placed to assume a leadership role in promoting and facilitating multicenter clinical research studies, including clinical trials. But financial constraints and complicated accounting policies often lead academic administrators to passively support or even actively discourage funding for personnel, facilities, patient enrollment, or equipment to conduct clinical research. Fortunately, nearly half of North American veterinary colleges have dedicated some support to clinical research activities, and several sponsor Offices of Clinical Trials.

Colleges that commit resources to generating new medical knowledge should benefit from the expertise and recognition afforded by such achievements. Clinical research is inseparable from high-quality patient care, and clients who choose hospitals associated with a clinical research program will benefit from the program's strengths. Thus, the patient base may increase, particularly if research activities are promoted as part of high-quality patient care.

A clinical research program also strengthens recruitment and retention of clinical faculty. For academic environments that support clinical research, the timing may be optimal to more effectively promote the role of spontaneous animal diseases as models of like diseases in people. Clinical trials involving veterinary patients might bridge the distance between mouse models and spontaneous disease in people.

Limited dissemination of information

Academia has successfully promoted the tenets of evidence-based medicine, and practitioners increasingly apply them to patient care. Indeed, practitioners help identify the questions that clinical research answers. Yet, despite our profession's enthusiastic embrace of evidence-based medicine, veterinary journal reports are often limited to case studies, case series, and review articles (largely based on human medicine) rather than clinical trials. This limitation is due, in part, to the paucity of clinical trial data. Anecdotal evidence appears to continue to play an important role in therapeutic decision-making in veterinary medicine. For example, veterinarians have rapidly accepted specialty compounded drugs, human generic drugs, and dietary supplements as therapeutic modalities despite limited or no evidence of efficacy or safety.

Poor study design

Disconcertingly, poor study design often weakens the validity of conclusions drawn from veterinary clinical trials. Many clinical trials lack appropriate controls, randomization of treatment groups, or blinding procedures. Statistical support is critical in well-designed trials but is often not used or is reserved until data have been collected. A common sequela of insufficient or late statistical input is that only a small number of patients are studied, which leads to two common errors.

  • First, investigators may use the same animal to study multiple therapeutic interventions. Thus, even if randomization and crossover are properly performed, the increased number of comparisons increases the risk that a difference will be falsely identified as significant.
  • Second, a small sample size decreases the power of the study to detect true treatment differences. The investigator, and practitioner, often confound the mistake by interpreting the lack of significant difference as evidence that the treatment groups are the same, and thus, the treatments are equivalent—or in the case of a placebo-controlled study that the treatment had no effect. It is a veterinarian's responsibility to learn what constitutes a well-designed clinical trial and to be able to assess the validity of the investigators' conclusions.