In a recent article in Pediatrics, Nils Songstad and colleagues examine the impact of a non-traditional “retrospective” consent process, versus the usual prospective consent process, on rates of recruitment, characteristics of enrolled subjects and study outcomes in the HIPSTER (Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants) study (10.1542/peds.2017-2092). HIPSTER was a randomized, un-blinded multicenter trial that compared high flow nasal cannula to continuous positive airway pressure (CPAP) as primary respiratory support for preterm infants that needed respiratory support but not intubation within 24 hours of birth. Preterm infants had to be enrolled within 4 hours of beginning CPAP, which was the standard treatment in the neonatal unit. A unique set of clinical trial circumstances facilitated this consent process comparison: HIPSTER’s study team initially asked their Ethics Committee (the Australian equivalent of US Institutional Review Board [IRB]) to approve a consent process that would allow randomization and initial treatment before parental consent could be obtained. The Ethics Committee (wisely I believe) asked the study team to conduct prospective consent for 3 months to be followed by an audit and a re-consideration of the question. The audit revealed that many parents were interested in study participation, but did not feel that they could decide as quickly as needed and with enough certainty to participate. The Ethics Committee then decided, with justification also based on Australian national guidelines, that a “deferred” or “retrospective” consent process was allowable.
In general, informed consent must be obtained before any research begins. The process of “retrospective consent” or of obtaining consent after study procedures have begun, is not specifically described in the US Code of Federal Regulations. There are guidelines for both (1)- emergency use of a test article (device or drug) and (2)-planned research in emergency settings with a waiver of consent, and HIPSTER was neither of these. Although the potential subjects (preterm infants) were ill and treatment was urgent, their surrogates (the parents) were mainly available and present. However, as our common sense tells us, and as Songstad and colleagues articulate clearly, the parents of potential subjects were stressed, distressed, and potentially in pain, so not in a mental and emotional state to rationally consider, or even want to consider, research, especially with a tight 4-hour timeline for a decision. Thus “retrospective consent,” also described as deferred consent, allowed the researchers to approach parents a bit later, in the first few days of life, and at a calmer moment. I won’t give you the “spoiler” here, and hope you will read the article to understand how and if the change impacted the population studied and the trial outcome.
The original HIPSTER trial was not primarily intended to examine the parental consequences of the differing consent methods. Thus, data about how parents felt about the two approaches was not gathered, but in future studies this would be important information for both the IRB and the study team in terms of utilizing “retrospective consent.” The Belmont Report outlines ethical guidelines for conduct of human subjects research and its first core principal is respect for persons, pragmatically operationalized in the informed consent process which underlines the key point that research is voluntary. Did “retrospective consent” increase, decrease or simply change the parents’ feeling that they had been fully consulted and that their autonomy with respect to their infant’s research participation was fully respected? That is the critical question that I believe deserves additional study, because so many vital