A new editorial in the PNEJM from 2 PhD ethicists. I specify that as they are not neonatologists, nor pediatricians nor yet medical researchers, and have no conflict of interest of any kind as far as I can see. Yet their criticism of the OHRP ruling is as severe as mine and as Dr Lantos’s (but in more measured language than mine!)
Their final statement is as follows:
‘…the OHRP is asking that research be described as riskier than it really is and is suggesting that the parents were duped into enrolling their frail infants in dangerous research. Not only is that not true, but it also poses substantial risk to the conduct of valuable comparative effectiveness research both for premature infants and for the general public’.
I sent an Op-Ed piece to the NY Times, as an attempt to balance what they had published; they appear not to have accepted it, so I will reproduce what I wrote below.
The editorial printed in the April 16 issue of the New York Times reports the findings of an OHRP investigation into a recent clinical research study. The editorial quotes the OHRP report, which noted that they determined ‘that the informed consent document for this trial failed to adequately inform parents of the reasonably foreseeable risks and discomforts of research participation.’
Neonatal Intensive Care has come a long way in the past 50 years. From the early days, the USA has been the world leader in pursuing improvements in care of sick preterm infants, and has been the country which has performed the most important research studies that have led to those improvements, here and around the world.
Unfortunately there remain many unknowns in how we should care for the infants who are born very prematurely. As a result there are great variations in practice around the country, and across the world. One of these variations, until recently, was the target ranges of oxygen saturation which, as noted in the editorial are usually between 85% and 95%, although they may even be higher or lower than these limits.
Until this study was performed there was no good reason for choosing one range over another; the study actually compared what happened if you used the upper part of this range which was already in use, to the lower part of the range.
In other words, no baby in the study was exposed to anything which was outside of usual clinical practice.
It is mistaken to think that there was a ‘standard of care’ prior to this study. Even now there is discussion about the best saturation target range, and there is no standard of care. This is one major failing of this report from the OHRP which mentions frequently ‘standard care’ and ‘standard of care’ without understanding that there was (and is) no such thing.
Your editorial supposes that an infant who needed a different oxygen range might have been given a different oxygen range, and could have been harmed as a result. This is untrue. Firstly there was no reason before this study to use one target range rather than another for an infant. Oxygen target ranges are not individualized in the NICU according to patient needs, they are standardized according to whether the baby is premature or not. Secondly if there were some unusual circumstances which made a doctor think that an individual baby did need a specific range of oxygen, then it is usual practice to take the baby out of the study, and give them the therapy (in this case a specific oxygen target range) that you think they need.
This report was developed after the study was completed and published, but at the time of the planning and performance of the study there was no reason to prefer one particular range of oxygen saturation over another. If it had already been known which oxygen saturation target level was preferable, the study would not have been done. The importance of this issue is demonstrated by the fact that a never before seen collaboration across the world, with, in addition to this trial, studies in Canada, the UK, Australia and New Zealand, a collaboration called ‘NeoProm’ was created to study the issue of oxygen saturation targeting, with very similar studies being done in all of those countries.
Research such as this study are essential for the future of care of the premature baby, and rulings such as this misguided opinion of the OHRP puts such research at risk.