Special considerations in the design, conduct and analysis of prophylaxis trials.

Methodological considerations in clinical trials apply to prophylaxis studies also. In addition, there are certain aspects that need special attention. These are the identification of a valid group of controls, the choice of the unit of randomization and its impact on subsequent analyses, the specificity and the sensitivity of case diagnosis and their impact on estimated efficacy and its reliability. The ethical aspects of the trial also need special consideration, bearing in mind that the intervention is on healthy individuals, and not patients with disease. These are discussed in the context of community prophylaxis trials of tuberculosis and leprosy undertaken in south India.