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Dealing with the unknown: reducing the proportion of unvalidated treatments offered to children
  1. Dominic Wilkinson1,2,3,
  2. Iain Chalmers4,
  3. Melinda Cruz5,
  4. William Tarnow-Mordi6
  1. 1Faculty of Philosophy, Oxford Uehiro Centre for Practical Ethics, University of Oxford, Oxford, UK
  2. 2Robinson Institute, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, Australia
  3. 3John Radcliffe Hospital, Oxford, UK
  4. 4James Lind Initiative, Oxford, UK
  5. 5Miracle Babies Foundation, Sydney, New South Wales, Australia
  6. 6WINNER Centre for Newborn Research, NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
  1. Correspondence to Dr Dominic Wilkinson, Oxford Uehiro Centre for Practical Ethics, Suite 8, Littlegate House, St Ebbes St, Oxford OX1 1PT, UK; dominic.wilkinson{at}

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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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