How should one analyse and interpret clinical trials in which patients don't take the treatments assigned to them?

Abstract

‘Obviously it is not practically possible to preselect two large strictly random groups of children who are representative of the general population and to insure that every child in one group receives the vaccine while every child in the other group receives no vaccine during the observation period. Children in the general population have the prerogative to refuse vaccine offered and the liberty to obtain other vaccine when desired. In these premises there is no known way of changing the two groups so that one would include only children actually vaccinated, and the other include only children not vaccinated, without destroying the randomness of the selection and to that extent possibly invalidating the answer to the question asked. After it has been established that the vaccine confers protection, then questions concerning the amount and duration of such protection might in part demand direct comparison of the experience of the children actually vaccinated with those not vaccinated, providing adequate data are at hand to equalize the two groups with respect to attributes which apparently influence the occurrence of the disease. For this report, the approach to the primary problem involved the preselection of two large strictly random groups of children and the subsequent injection of a large proportion of only one group with the vaccine. All analyses herein presented are a comparison of the experience of such preselected groups regardless of their actual status with respect to receiving the vaccine. The difficulties encountered in this approach are chronologically described in detail so that the reader may evaluate any possible errors involved.’