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No child left behind: Enrolling children and adults simultaneously in critical care randomized trials*

Halpern, Scott D. MD, PhD, M.Bioethics; Randolph, Adrienne G. MD, MSc; Angus, Derek C. MD, MPH

doi: 10.1097/CCM.0b013e3181a59357
Pediatric Critical Care

Objective: Randomized clinical trials of novel critical care interventions are currently tested in children only after documenting their safety in adults. Although this practice may protect children from research risks, it may paradoxically threaten children’s well-being by depriving them of evidence to guide their care. We sought to evaluate the ethical, methodologic, and practical arguments for and against studying critical care interventions in adults and children simultaneously rather than sequentially.

Data Source: Empirical studies and conceptual arguments germane to the objective were reviewed.

Data Extraction and Synthesis: Children are traditionally viewed as “participants of last resort” due to their vulnerability and decisional incapacity. However, critically ill adults commonly share similar features. Thus, structured risk assessments used by Institutional Review Boards to determine the adequacy of research protections for critically ill adults can also help protect children. From a methodologic perspective, interventions may be tested simultaneously in children and adults by enrolling children as a prespecified subgroup within a larger adult randomized clinical trial or by enrolling children in a separate trial conducted in parallel. Both approaches raise practical and analytical challenges that can frequently be met. For example, investigators might choose outcome measures that are appropriate for both adults and children. Additionally, using Bayesian approaches to link the estimates of treatment effects in children to the values observed in adults may enhance the statistical power to detect pediatric-specific effects. Finally, centralized Institutional Review Boards and data monitoring centers may alleviate practical concerns with conducting trials among adults and children simultaneously.

Conclusions: The current standard of testing critical care interventions in adults before children rests on tenuous ethical arguments and is entrenched by the methodologic and logistic barriers encountered with alternative approaches. However, these barriers will frequently be surmountable. We therefore propose that the default paradigm be changed such that interventions are examined routinely in critically ill children and adults simultaneously unless unique reasons exist to the contrary.

From the Division of Pulmonary, Allergy, and Critical Care Medicine (SDH), Center for Bioethics (SDH), Center for Clinical Epidemiology and Biostatistics (SDH), and Leonard Davis Institute of Health Economics (SDH), University of Pennsylvania School of Medicine, Philadelphia, PA; Division of Critical Care Medicine (AGR), Department of Anesthesia, Harvard Medical School and Children’s Hospital Boston, Boston, MA; Department of Critical Care Medicine (DCA), University of Pittsburgh School of Medicine, Pittsburgh, PA.

This work was supported, in part, by a Greenwall Foundation Faculty Scholar Award in Bioethics (SDH) and Grant NIGMS P50 GM076659 from the National Institute of General Medical Sciences (DCA).

The authors have not disclosed any potential conflicts of interest.

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© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins