finding above. The problem with making conclusions taking into account level of participation is that the participants with greater involvement may have a higher baseline risk than those with more limited or no participation, and therefore those who self-select into the intervention could end up having worse outcomes than those who do not participate, regardless of intervention effect.
The design and analysis of studies can aid in distinguishing the effect of the intervention from the effects of self-selection. Individual participation can be measured only in those randomized to the intervention group, because those in the control group are not offered the opportunity to participate. Nevertheless, a randomized trial design makes it possible to treat the control group as a mixture of would-be participants and would-be nonparticipants. Thus, with appropriate assumptions, it is possible to arrive at causal inferences about the intervention effect on those who would be participants in an intervention. This is an example of the general approach called “principal stratification” (Bloom, 1984; Angrist, Imbens, and Rubin, 1996; Frangakis and Rubin, 1999, 2002; Jo and Muthén, 2001; Jo, 2002; Jo, Asparouhov, et al., in press). Such analyses are extremely valuable in that they characterize not only the effects of an intervention on participants, but also who chooses to participate in an intervention.
In treatment studies, the existing standards for ethical conduct of research dictate that it is improper to withhold an effective, safe treatment from participants. Thus because there are successful treatments for schizophrenia, it would be inappropriate and unethical to evaluate a new antipsychotic drug in a randomized trial that assigned some psychotic individuals to receive a placebo. The ethical considerations are different, however, in testing an antipsychotic drug for its ability to prevent schizophrenia or psychotic episodes in individuals exhibiting prodromal or preclinical signs or symptoms of schizophrenia. Although a few small randomized trials suggest that low-dose resperidone along with family therapy may provide some preventive value for adolescents who are at high risk for developing schizophrenia (McGorry, Yung, et al., 2002), the potential for causing side effects or otherwise harming individuals with these powerful drugs must be considered. In the case of a disorder that has not yet been manifest and an intervention that is known to have significant side effects, “doing no harm” has to be considered in order to decide whether it is ethical to conduct this kind of trial.
One potential way to deal with some of these ethical concerns, when there is a very real possibility of doing harm, is to use a mediational model