Intervention studies

Readings

• Dohoo I, Martin S, Stryhn H (2003) Veterinary Epidemiologic Research. AVC Inc, Charlottetown, Prince Edward Island, Canada. pp 185 - 206 (controlled trials).
• Thrusfield M (2005) Veterinary Epidemiology. Blackwell Science, London. Chapter 16 (clinical trials).
• Committee for Proprietary Medicinal Products (2000) Points to consider on switching between superiority and non-inferiority. The European Agency for the Evaluation of Medicinal Products, London.
• Moher D, Schulz KF, Altman DG (2001) The CONSORT statement: Revised recommendations for improving the quality of reports of parallel group randomised trials. Annals of Internal Medicine 134: 657 - 662.

Presentations

• Key considerations in designing an intervention study.
• Outcome measures: compare non-inferiority, superiority and equivalence trials; discuss power, p-values and confidence intervals when interpreting results.
• Vaccine trials: vaccine efficacy, herd immunity, unit of interest, atomistic and ecological fallacies.
• Control of biase when conducting clinical trials (randomisation, blinding).

Exercises

Read and assess the following papers (or any other recent papers you may find). You can use the CONSORT checklist to help with this:

• Dias PT, Alders RG, Fringe R and Mata BV (YYYY) Laboratory and Field Trials with Thermostable Live Newcastle Disease Vaccines in Mozambique.
• Cusack P (2004) Effect of mass medication with antibiotics at feedlot entry on the health and growth rate of cattle destined for the Australian domestic market. Australian Veterinary Journal 82: 154 - 156.
• Williamson JH, Woolford MW, Day AM (1995) The prophylactic effect of a dry-cow antibiotic against Streptococcus uberis. New Zealand Veterinary Journal 43: 228 - 234.
• Karpathy RC, Firth GA and Tannock GA (2003) Field evaluations of safety and efficacy of an Australian Marek's disease vaccine. Australian Veterinary Journal 81: 222 - 225.

Example examination questions

1. A new genetically engineered vaccine has recently been developed for infectious bronchitis virus in poultry. This vaccine can be applied to individuals as day-old chicks or as a mass vaccination. It has undergone extensive laboratory evaluation and the developers are now ready to commence field trials under commercial conditions. You have been asked to design a field study to evaluate the efficacy of the vaccine in preventing mortalities and production losses in commercial broiler enterprises. Describe how you would proceed (2001 written).

2. A live avirulent Toxoplasma vaccine is very effective in preventing Toxoplasma abortions in sheep. Toxoplasma gondii is closely related to Neospora caninum, so it is possible that the live Toxoplasma vaccine would be efficacious against Neospora abortions in cattle. This hypothesis requires investigation and a field trial is desired. Describe how you could investigate the efficacy of the sheep Toxoplasma vaccine in preventing bovine Neospora abortions using a field trial approach (2000 written).

3. You are a consultant to a veterinary pharmaceutical company that is about to try and register a new product for the treatment of osteoarthritis in dogs. The new product is a different formulation of the same active ingredient as an existing product already on the market. Accordingly, the company wants registration on the basis that the two products are equally effective. A clinical trial is required and a number of veterinary practises in Australia are available to assist. Describe in detail the study or studies that you would recommend in this situation (1999 written).

4. Write brief notes, using examples, to demonstrate your understanding of matching in clinical trials (1995 written).

Additional reading

• Jones B, Jarvis P, Lewis JA and Ebbutt AF (1996) Trials to assess equivalence: the importance of rigorous methods. British Medical Journal, 313: 36 - 39.
• Beller EM, Gebski V, Keech AC (2002) Randomisation in clinical trials. Medical Journal of Australia 177: 565 - 567.
• Altman DG, Bland JM (1995) Absence of evidence is not evidence of absence. British Medical Journal 311: 485.
• Dohoo IR Thomas FC (1989) Clinical trials in veterinary medicine. Canadian Veterinary Journal 30: 291 - 303.
• Baldock C (1991) New Approaches to disease investigation. An update on clinical trials. In: Dairy Medicine and Production, Proceedings 161, Postgraduate Committee in Veterinary Science, University of Sydney, pp 423 - 437.
• Hedges J, Blowey R, Packington A, O'Callaghan C, Green L (2001) A longitudinal field trial of the effect of biotin on lameness in dairy cows. Journal of Dairy Science 84: 1969 - 1975.