Indications and requirements for the use of prerandomization

Although in effectiveness studies, the conventional randomized trial, in which informed consent is obtained before randomization, is the first choice, this design is not the panacea for all research questions. To counter contamination problems, prerandomization designs might be an alternative. Prerandomization implies that the randomization takes place before seeking informed consent, and because of this, prerandomization designs are controversial among ethicists, health lawyers, methodologists, and clinicians. However, in the Netherlands, these designs are becoming more accepted since the Dutch State Secretary of Health, Welfare and Sport decided that, under certain circumstances, prerandomization is admissible and not in conflict with the law.

Based on well-defined indications and requirements, guidelines for the optimal application of prerandomization designs are presented. Designs in which prerandomization is used are outlined; methodological considerations useful when conducting trials using conventional designs or prerandomization designs are discussed, in addition to ethical and judicial aspects.

In certain situations, prerandomization designs have an essential contribution to achieve evidence-based medicine. Banning prerandomization a priori implies that information about the effectiveness of numerous public health and medical interventions will not be forthcoming. Therefore, every design should be based on a balance between maximizing the potential for patient autonomy and minimizing the bias caused by contamination. This balance cannot be reached by formulating general rules, but an independent group of experts, like members of research ethics committee (REC), should decide whether this balance is acceptable.