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The practice of veterinary medicine has always lagged behind human medicine. New treatments or diagnostic modalities that swiftly become mainstream practice in human medicine are often slow to percolate through to veterinary practitioners. This time delay occurs for many reasons, including drug costs and lack of access to specialist equipment. However, the veterinary profession must seize the opportunity to translate the new and exciting advances in the diagnosis and treatment of human disease to veterinary patients, or even better, to develop novel therapies, for use in our own patients.

Over the last decade the veterinary profession has started to recognise the importance of evidence-based medicine. We are coming to understand the difference between clinical practice based upon learned opinion (personal experience) and that which is based upon the results of scientific investigation (clinical research). This distinction is of critical importance. We are moving away from a reliance on received wisdom and dogma, the source of which can be either obscure or based on anecdotal evidence. Instead we are questioning the dogmas and seeking to answer these questions with well constructed and reasoned studies.

Accurate observation underpins accurate science. The observation of one individual is still of great importance (so there will always be room for the case series in biomedical journals). However, in order to understand whether the observations in a small case series can be applied to a broader population the conclusions need to be tested and validated. An infinite number of variables can influence the progression of an individual case (bias); if conclusions are to be applied to a general population, we therefore must employ strategies to reduce the impact of such variables.

One strategy to reduce bias is collaborative research. This means investigations are performed using the joint intellectual effort and resources of multiple investigators at multiple institutions. By doing this potential biases such as demography (patient factors) and clinical technique (practitioner/investigator factors) can be diluted. Larger numbers of cases can be recruited reducing the impact of anomalous cases and increasing the statistical power of the study. In addition, the recruitment of cases in a shorter time frame enhances the consistency in case management at multiple sites.

Techniques used in clinical research to improve the validity of the conclusions drawn from larger studies include: randomisation of patients to treatment arms, blinding of investigators to the specific intervention applied and the use of a placebo control to be compared with the treatment under investigation. Indeed, the randomised, double-blinded, placebo-controlled clinical trial represents the keystone of current medical research. It is perhaps disappointing that a search of veterinary literature revealed only thirteen randomised controlled clinical trials in cats and dogs (with a total of 1157 cases). Eleven of these studies were multicentre investigations. Selected papers (with more than 100 cases) are provided in the references section (Ettinger and others 1998, Kvart and others 2002, Granholm and others 2006, King and others 2006). By contrast, a single randomised controlled double-blinded clinical trial in human beings specifically comparing the selective oestrogen receptor modulator agents tamoxifen and raloxifene following surgery for breast cancer, enrolled a total of 19 747 patients (Vogel and others 2006)!

Collaborative research is clearly beneficial to the advancement of science. In addition, clinical research projects often require additional funding and larger collaborative groups may be looked upon more favourably in their approach to funding bodies.

A collaborative UK body has been created to improve research in veterinary oncology. The stated objectives of the Veterinary Oncology Research Cooperative (VORC) are:

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    To develop a multi-institute, multi-disciplinary group of clinicians and scientists that freely share clinical case material, clinical samples, clinical data, laboratory reagents and laboratory techniques and skills.
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    To accelerate each individual member’s research goals and provide large case numbers for oncology-related studies, by the free and open exchange and sharing of the group’s resources.
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    To foster and encourage an atmosphere of mutual trust, transparency and openness within the group, thereby engendering inter-institute cooperation rather than competition.

Collaboration has its advantages but it also introduces other problems. The success of any such venture depends entirely upon participants’ willingness to be open with their plans and their criticisms. Thus VORC is a group without internal hierarchy and in which all project participation is entirely voluntary. Projects will succeed or fail on the basis of the group’s collective interpretation of their interest value and scientific validity. Frank discussion drawing on relatively disparate expertise and experiences may lead to the termination of some investigations whilst still in the conception stage.

For successful projects, authorship accreditation could be a divisive issue. On one hand, it can be a source of considerable irritation to the individuals involved if they have had significant input into a project’s design or execution and have not been acknowledged by inclusion in the author list. On the other hand, the integrity of the publication process and of a collaborative body such as VORC requires that all listed co-authors have made substantive contributions to design, execution and presentation of a study. To circumvent potential problems, authorship of ensuing publications must be discussed at the outset of all projects. Inclusion in the author list is determined by the principal investigator but would likely require contribution of a specified proportion of case material or other resources and a meaningful contribution to the subsequent manuscript.

VORC had its inaugural meeting during the BSAVA Congress in April 2005; there were twenty interested individuals present representing many different disciplines, including specialist oncologists, epidemiologists, scientists, pathologists, surgeons and medics from academia and referral and private practice.

Through regular meetings a cohesive network of like-minded investigators has been generated. This enables frank and open discussion of many issues and has already led to agreed protocols for treating a number of different small animal cancers, including canine lymphoma and osteosarcoma. This standardisation will facilitate assessment of future novel treatments by comparison with an accepted regime.

Although it is still very early days for VORC, the relative ease in which interested parties came together in the spirit of sharing and cooperation, and the enthusiasm of its members bode well for the group’s success. We would encourage other subject specialties to generate similar cross-institutional, cross-disciplinary groups and to make the best use of our national resource!

References

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  2. References
  • Ettinger, S. J., Benitz, A. M., Ericsson, G. F., Cifelli, S., Jernigan, A. D., Longhofer, S. L., Trimboli, W. & Hanson, P. D. (1998) Effects of enalapril maleate on survival of dogs with naturally acquired heart failure. The Long-Term Investigation of Veterinary Enalapril (LIVE) Study Group. Journal of the American Veterinary Medical Association 213, 1573-1577
  • Kvart, C., Haggstrom, J., Pederson, H. D., Hansson, K., Eriksson, A., Jarvinen, A. K., Tidholm, A., Bsenko, K., Ahlgren, E., Ilves, M., Ablad, B., Falk, T., Bjerkfas, E., Gundler, S., Lord, P., Wegeland, G., Adolfsson, E. & Corfitzen, J. (2002) Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation. Journal of Veterinary Internal Medicine 16, 80-88
  • Granholm, M., Mckusick, B. C., Westerholm, F. C. & Aspegren, J. C. (2006) Evaluation of ther clinical efficacy and safety of dexmedetomidine or medetomidine in cats and their reversal with atipamezole. Veterinary Anaesthesia and Analgesia 33, 214-223
  • King, J. N., Gunn-Moore, D. A., Tasker, S., Gleadhill, A. & Strehlau, G. (2006) Tolerability and efficacy of benazepril in cats with chronic kidney disease. Journal of Veterinary Internal Medicine 20, 1054-1064
  • Vogel, V. G., Costantino, J. P., Wickerham, D. L., Cronin, W. M., Cecchini, R. S., Atkins, J. N., Bevers, T. B., Fehrenbacher, L., Pajon, E. R. Jr, Wade, J. L. III, Robidoux, A., Margolese, R. G., James, J., Lippman, S. M., Runowicz, C. D., Ganz, P. A., Reis, S. E., Mccaskill-Stevens, W., Ford, L. G., Jordan, V. C. & Wolmark, N. (2006) Effects of tamoxifen vs raloxifene on the risk of develoing invasive breast cancer and other disease outcomes. The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial. Journal of the American Medical Association 295, 727-2741

Gerry Polton is a veterinary oncologist at Davies Veterinary Specialists. His primary area of scientific interest is anal sac gland carcinoma in the dog.

Tim Scase is a senior lecturer in veterinary pathology at the Department of Veterinary Medicine, University of Cambridge. His main research interest is the molecular pathology of tumours.