The November 2014 Ethics Rounds questioned: “When is waiver of consent appropriate in a neonatal clinical trial?” As neonatal clinical trialists, we believe that a waiver of prospective informed consent is often required and ethically appropriate to conduct scientifically rigorous delivery room clinical trials.
As Drs Wootton, Arnold, and Tyson acknowledged, many emergency therapies have never been rigorously studied. Neonatal resuscitation medicine is especially bereft of high-level evidence. Only 23 of 157 (15%) publications cited in the 2010 ILCOR statement on neonatal resuscitation were randomized trials or meta-analyses of trials (level of evidence [LOE] 1) (Table 1). In contrast, 114 (73%) studies lacked a control group (LOE 4), or worse, were performed in a different population, in animals, or in a mechanical model (LOE 5).1 We urgently need well-designed studies of the safety and efficacy of delivery room interventions in newborns.
The delivery room presents unique challenges to study enrollment. Neonatal resuscitation occurs immediately after birth, so prospective informed consent must be obtained before delivery. However, predicting the timing of birth is imprecise. Hence, infants born precipitously or to acutely ill mothers are often excluded from trials that use antenatal consent, which threatens the generalizability of delivery room trials.2
A waiver of prospective informed consent may be appropriate when the research could not be feasibly conducted otherwise, such as emergency research. However, in the November article, Dr Schreiner argued that a neonate would not meet the 1996 OPRR requirements for waiver of consent in emergency research because a legally authorized representative is always present in the delivery room. This statement erroneously conflates a parent's physical presence with the ability to participate in an informed consent discussion. The pregnant mother's physical status or concurrent therapy may preclude the ability to provide informed consent. Furthermore, in many scenarios resulting in need for neonatal resuscitation, there is inadequate time to obtain antenatal informed consent.3 When antenatal consent is not possible, we propose that eligible subjects be enrolled in delivery room studies, followed by a request for informed consent from parents for ongoing study participation as soon as possible after enrollment. This process, called “deferred” or “retrospective” consent in some countries, still allows for some parental participation.
This is not to deny that neonates are a vulnerable population who deserve special regulatory protection. Nonetheless, it is imperative that the desire to protect this population does not perpetuate the use of inadequately studied and potentially dangerous interventions. A waiver of prospective informed consent is often necessary and appropriate to conduct scientifically and ethically sound delivery room trials. We believe that institutional review boards frequently do not balance this consideration.
Conflict of Interest: None declared
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- Copyright © 2015 by the American Academy of Pediatrics