Session D: Delivery room research and the challenges for informed consent

Sara F. Goldkind, M.D., M.A.
Goldkind Consulting, L.L.C.
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Mark S. Schreiner, M.D.
The Children’s Hospital of Philadelphia
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From an IRB chair’s perspective, approving delivery room research is not especially problematic. The data supporting the efficacy and safety of many current treatments, as well as choices between competing treatments, are often inadequate. Clinicians and investigators, therefore, are often in a state of clinical equipoise that justifies the conduct of a proposed trial.

In this presentation, Dr. Schreiner notes that unpredictable emergencies that require immediate intervention do not easily lend themselves to a true informed consent process. The IRB’s challenge is thus to determine the appropriate requirements for parental permission. Investigators are obligated to provide the IRB with a detailed discussion justifying their plans. Some of the questions investigators must address include:

• Is an “emergency” situation truly unpredictable? Some DR emergencies can be anticipated, and consent obtained beforehand. For a hypothetical trial in the DR involving non-vigorous infants born through meconium stained amniotic fluid, several authors argued that it was impracticable to obtain consent in this setting. Subsequently, Chettri et al. demonstrated that it was indeed possible to obtain consent in a trial identical to the hypothetical one.
• Are interventions no more than minimal risk? There is considerable controversy regarding both the meaning of minimal risk, and which risks are foreseeable. This discussion is frequently raised for comparative effectiveness research involving two or more “standard care” interventions. IRBs adhere to the definitions and conclusions of OHRP’s draft guidance on foreseeable risk to guide their determinations.
• When the risks of a proposed intervention are greater than minimal, and the newborn would be in a “life-threatening situation, available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence, which may include evidence obtained through randomized placebo-controlled investigations, is necessary…” The research might qualify for an exception from the requirements for informed consent (EFIC). Approval of a waiver under EFIC, however, does not remove all obligation to obtain consent or confirm permission. When there is enough time, investigators are still obligated to obtain informed consent; when there is not, investigators still must try to contact the family to allow them the opportunity to opt-out. Since at least one parent (at a minimum) is always present in the DR, investigators must allow the parent(s) to opt-out.

Neil Finer, M.D.
Sharp Mary Birch Hospital for Women and Newborns
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Research conducted in the delivery room is unique for several reasons: 1) there are always at least two patients (and sometimes more), each of whom are considered especially vulnerable, and 2) the actual circumstances of the delivery and support requirements for the mother and infant(s) cannot be accurately predicted beforehand. Thus, research studies, especially randomized interventional trials which would require consent from the parent(s) before the intervention, present challenges.

Approaching a mother in labor to discuss a trial consent is an added stress at an already stressful time, especially if the mother is in preterm labor or about to deliver an infant about whom there is significant concern. In addition, previous studies have determined that infants born to mothers approached for consent had better overall outcomes than mothers who were not available for consent. This suggests that such trials may favor advantaged populations and miss the most vulnerable infants. Many trials are presently attempting to determine best practice from current approaches; where these alternate approaches are both considered to be of minimal risk, waiver of consent is an option. With the ability to use waivers comes novel and infrequently used design possibilities.

In this presentation, Dr. Finer describes one such approach, the randomized cluster cross-over (RCC) study. The RCC studies attempt to evaluate optimal initial oxygen concentrations for premature newborn infants requiring resuscitation, and have now been funded for a comparative study of immediate cord clamping versus cord milking for non-vigorous term and near-term infants utilizing the RCC approach. Dr. Finer argues that there is a need for using more pragmatic study designs and waivers of consent, where appropriate, to encourage participation of both physicians and potential study subjects. Moreover, the definition of risk, which is both pragmatic and clinically relevant, is a key consideration in any comparative trial, and requires significant deliberation.

David H. Strauss, M.D.
Austen Riggs Center
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Christine Grady, R.N., Ph.D., F.A.A.N.
National Institutes of Health Clinical Center
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Gregory E. Simon, M.D., M.P.H.
Kaiser Permanente Washington Health Research Institute
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Sara F. Goldkind, M.D., M.A.
Goldkind Consulting, L.L.C.
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In this closing session of the workshop, session moderators will come together as a panel to provide their personal perspectives on the challenges of informed consent, as well as highlights and summary of the discussions that took place in their sessions.