. "4 Defining, Interpreting, and Applying Concepts of Risk and Benefit in Clinical Research Involving Children." The Ethical Conduct of Clinical Research Involving Children. Washington, DC: The National Academies Press, 2004.
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Ethical Conduct of Clinical Research Involving Children
assigned to either a placebo-control group (with no benefit expected) or a group receiving an experimental intervention (with a prospect of benefit). (The same kind of explanation is also necessary when active treatment control groups are employed.) Parents should also be informed if children in the placebo-control group will eventually “cross over” to the experimental intervention. They should likewise be provided clear explanations about why a placebo arm is necessary to answer the research question and what measures that will be taken to ensure the child’s safety and well-being. As discussed in the next chapter, studies indicate that research participants and parents of research participants may not understand these and other aspects of research.
Given the controversy over placebo-controlled trials, more published data are needed on health outcomes for research participants receiving placebos. A common misperception among patients (and even some clinicians) is that research participants assigned to placebo arms are necessarily at greater risk than those assigned to treatment arms. Particularly in early-phase studies, however, the participants in placebo arms may have fewer adverse events. As discussed above, if the condition of research equipoise is indeed met, then no research participants should be exposed to treatment (including administration of a placebo) known to be inferior to an alternative.
Assessing Whether Risk Is Minimized
One ethical and regulatory responsibility of investigators is to minimize the risk that research presents to participants. In assessing whether risks are being minimized, attention often focuses on the risk presented by the procedures or interventions that are being tested for safety or efficacy. Investigators and reviewers must, however, also consider whether risks are minimized for interventions or procedures intended solely to collect information (e.g., blood draws and lumbar punctures). One advantage of separately evaluating each intervention or procedure in a research protocol, as recommended above, is that it encourages attention to risk minimization for all the procedures.
As observed in Chapter 1, poorly designed research will usually fail to answer the research question. One example is research that is designed without adequate attention to the sample size needed to detect a meaningful difference between an experimental intervention and a placebo or control treatment. At a minimum, such research wastes the time of research participants. Depending on its particular faults, poorly designed research can also expose research participants to avoidable harm and can dissipate potential benefits. An important emphasis of specialized education for clinical re-