to predict who is likely to benefit most from this type of antipsychotic drug. This type of mediation design (Pillow, Sandler, et al., 1991) uses the trial’s inclusion/exclusion criteria to limit the trial to those whose signs or symptoms most closely match those targeted by the intervention. Limiting participants in the trial to those with prodromal symptoms as well as brain abnormalities associated with schizophrenia identifiable by magnetic resonance imaging, for example, may tip the benefit-cost ratio sufficiently to justify a trial (with appropriate consent) of a potentially risky pharmacological intervention. The burgeoning availability of genetic and other biological information with tenuous links to specific disorders also elevates ethical considerations (see Chapter 5).
Sometimes a design that would clearly be unethical or impractical with individual-level random assignment can be appropriate if conducted with group-level random assignment. This approach was used for practical reasons in a large preventive trial aimed at preventing the spread of HIV among Thai military conscripts through changes in sexual practices. Rather than randomly assign individuals in the same company to two different conditions, companies were matched within battalions and then randomly assigned to an active behavioral intervention or a passive diffusion model (Celentano, Bond, et al., 2000). Part of the rationale in such studies is that a community-wide preventive intervention cannot be implemented across a country at the same time, thus randomly assigning some of the communities to this intervention deviates from what would normally happen simply by using a fair method of assigning which communities receive the intervention first.
In many situations, a community or government agency decides that all its young people should receive a new preventive intervention, even though the intervention itself has not yet been well evaluated. Indeed, in suicide prevention, for which few programs have been evaluated rigorously, communities frequently decide to saturate the community with a program. Under certain circumstances it is still possible to evaluate the effectiveness of such an intervention using a randomized design. For example, a standard wait-list design can be used to randomly assign half of the participants or groups to receive the intervention immediately and half to receive it later.
Communities are often accepting of a standard wait-list design because there are benefits to both conditions: a community that initially receives the intervention has an opportunity to benefit immediately; the community with a delayed start has the opportunity to benefit from any enhancements of the intervention made on the basis of the initial experience. A disadvan-