Despite long-standing critiques of the conduct of underpowered clinical
trials, the practice not only remains widespread, but also has garnered increasing
support. Patients and healthy volunteers continue to participate in research
that may be of limited clinical value, and authors recently have offered 2
related arguments to support the validity and value of underpowered clinical
trials: that meta-analysis may "save" small studies by providing a means to
combine the results with those of other similar studies to enable estimates
of an intervention's efficacy, and that although small studies may not provide
a good basis for testing hypotheses, they may provide valuable estimates of
treatment effects using confidence intervals. In this article, we examine
these arguments in light of the distinctive moral issues associated with the
conduct of underpowered trials, the disclosures that are owed to potential
participants in underpowered trials so they may make autonomous enrollment
decisions, and the circumstances in which the prospects for future meta-analyses
may justify individually underpowered trials. We conclude that underpowered
trials are ethical in only 2 situations: small trials of interventions for
rare diseases in which investigators document explicit plans for including
their results with those of similar trials in a prospective meta-analysis,
and early-phase trials in the development of drugs or devices, provided they
are adequately powered for defined purposes other than randomized treatment
comparisons. In both cases, investigators must inform prospective subjects
that their participation may only indirectly contribute to future health care
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