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The frontispiece of Bill Silverman's book Retrolental fibroplasia: a modern parable is an image of the 12th century Jewish Arab polymath Mu¯sa¯ ibn Maymu¯n (Moses Maimonides).1 Maimonides holds a book with the following inscription: “Teach thy tongue to say ‘I do not know’ and thou shalt progress.” What does it mean to declare ‘I do not know’? Famously, former US Secretary of State for Defence Donald Rumsfeld, distinguished three situations:
There are things we know that we know. There are known unknowns. That is to say there are things that we now know we don't know. But there are also unknown unknowns. There are things we don't know we don't know.2
When, on the basis of up-to-date, well-conducted systematic reviews of relevant evidence, we know we do not know and yet we fail to act, people have suffered and died unnecessarily. For example, the consequence of decade-long delays in addressing uncertainties about the long-term effects of fetal exposure to antibiotics given to women in preterm labour is that many individuals are living today with cerebral palsy that could have been avoided.3
Paediatricians have been better than other medical specialists in acknowledging and addressing uncertainties.4 The long-standing integration of evaluative research as an expected element in paediatric oncology is rightly held up as a model of serial evaluation of proposals for new treatment regimens; and this feature of routine practice has been fundamental in transforming the outlook for children with disease that was formerly rapidly fatal. The way that the paediatric haematological oncologists have organised their practice has meant that inferior as well as superior new treatments have been identified more efficiently than they have been in other medical specialties. This is important because new treatments for cancers in children5 and for other conditions6 are …
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Contributors DW conceived of the paper and wrote an initial draft. IC, MC and WTM commented on drafts of the manuscript, edited the paper, and approved the final version for publication.
Funding DW was supported for this work by a grant from the Wellcome trust, [086041/Z/08/Z]. The funders had no role in the design or conduct of this study, collection, management or analysis of data, nor in preparation, review or approval of this manuscript.
Competing interests WTM was a chief investigator on the Australian and New Zealand BOOST II oxygen saturation targeting trials and many other neonatal randomised controlled trials. IC chaired the data safety monitoring committee for the UK BOOST II trial.
Provenance and peer review Commissioned; externally peer reviewed.
↵i However, as OHRP noted, the trial information leaflet appropriately disclosed (29 May 2008 version, p.5) that the CPAP (Continuous Positive Airways Pressure) or intubation or surfactant arm of this randomised 2×2 factorial trial carried a risk of resuscitation, chest compressions and even death. Every parent was thus informed, before random allocation of treatments, that the SUPPORT trial entailed this risk.
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