Preventive Trials for Disorders with Low Prevalence

The prevention field still has relatively little information about effective interventions for conditions that occur infrequently. In designing prevention trials for low-base-rate disorders and outcomes, such as schizophrenia (Faraone, Brown, et al., 2002; Brown and Faraone, 2004) and suicide (Brown, Wyman, et al., 2007), the sample sizes necessary to obtain sufficient statistical power often seem prohibitively large. For example, a universal preventive trial aimed at a 50 percent reduction in youth suicide in the general population would require more than 1,000,000 person-years of observation. Although a study this large is often considered impractical, some novel alternatives exist. One approach is to combine data across a cluster of similar trials by using a common outcome, such as death from suicide or unintentional causes, for a long-term follow-up assessment. Data on mortality outcomes can be collected relatively cheaply using the National Death Index. An approach that aggregates data across studies will have to take into account variation in impact across studies with random effects, just as in meta-analysis (Brown, Wang, and Sandler, 2008).

An important strategy that other health fields use to test interventions on low-base-rate outcomes is to assess the impact of the intervention on a more common surrogate endpoint that has been identified as an antecedent risk factor for the outcome of interest. The rate of HIV seroconversion, for example, is sufficiently low in the general U.S. population that most HIV prevention trials use a reduction in HIV risk behavior as their primary outcome. Likewise, suicide attempts can serve as a surrogate for suicide itself, because there are roughly 100 times more suicide attempters than suicide completers, and attempt is a strong predictor of future suicide. The use of suicide attempts as an outcome would allow for sufficient statistical power with a much smaller study population.

Evaluating the Components of Interventions and Adaptive Interventions

Trials to examine the functioning of distinct components of an intervention may be needed, as when a comprehensive prevention program, such as Life Skills Training (see Box 6-1), has multiple components or modules that have been incorporated over the years. Although an intervention is normally tested in its entirety, the contribution of separate components can be examined through such approaches as study designs that deliver selected components (Collins, Murphy, and Bierman, 2004) or by examining the strength of different mediational pathways (West, Aiken, and Todd, 1993; West and Aiken, 1997).

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