1. NHS Evidence – provided by NICE Where can treatment uncertainties come from, and what do we do with them? Mark Fenton James Lind Initiative, Oxford Editor, UK Database of Uncertainties about the Effects of Treatments Thursday 19 th April 2012

2. NHS Evidence – provided by NICE Types of uncertainty about the effects of treatments ‘We’re uncertain whether anyone knows the effects’ uncertain uncertainty ‘We’re uncertain what the effects will be on you’ stochastic uncertainty ‘We’re uncertain because we don’t know your values’value uncertainty ‘We’re uncertain because no-one knows the effects’ certain uncertainty

3. NHS Evidence – provided by NICE “As we know, there are known knowns. There are things we know we know. “We also know there are known unknowns. That is to say we know there are some things we do not know. “But there are also unknown unknowns, the ones we don't know we don't know.” Donald Rumsfeld One creditworthy contribution to posterity: identifying different types of uncertainty

4. NHS Evidence – provided by NICE Patient/Population Intervention Comparison Outcome What is an uncertainty?

5. NHS Evidence – provided by NICE Good Medical Practice is the core ethical guidance the GMC provides to doctors. It is also intended to let the public know what they can expect from doctors

6. NHS Evidence – provided by NICE

7. Austin Bradford Hill, 1965 Four questions to which readers want answers when reading reports of research. 1. Why did you start? 2. What did you do? 3. What answer did you get? 4. And what does it mean anyway?

8. NHS Evidence – provided by NICE What are the effects of methylxanthines (caffeine, theophylline) for apnoea of prematurity?

9. NHS Evidence – provided by NICE The results of five trials that enrolled a total of 192 preterm infants with apnea indicate that methylxanthine therapy leads to a reduction in apnea and use of IPPV in the first two to seven days. The effects of methylxanthines on long- term outcomes will be addressed in data from the trial awaiting assessment.

10. NHS Evidence – provided by NICE Long-Term Effects of Caffeine Therapy for Apnea of Prematurity Barbara Schmidt, M.D., Robin S. Roberts, M.Sc., Peter Davis, M.D., Lex W. Doyle, M.D., Keith J. Barrington, M.D., Arne Ohlsson, M.D., Alfonso Solimano, M.D., Win Tin, M.D., for the Caffeine for Apnea of Prematurity Trial Group Conclusions Caffeine therapy for apnea of prematurity improves the rate of survival without neurodevelopmental disability at 18 to 21 months in infants with very low birth weight Volume 357:1893-1902 November 8, 2007 Number 19November 8, 2007

11. NHS Evidence – provided by NICE What are the effects of prophylactic antibiotics for inhibiting preterm labour with intact membranes?

12. NHS Evidence – provided by NICE This review fails to demonstrate a clear overall benefit from prophylactic antibiotic treatment for preterm labour with intact membranes on neonatal outcomes and raises concerns about increased neonatal mortality for those who received antibiotics… The 17 citations awaiting classification may alter the conclusions of the review once assessed.

13. NHS Evidence – provided by NICE

14. Because uncertainties about the long term effects of prescribing antibiotics in spontaneous preterm labour and caffeine for apnoea of prematurity were not investigated 25 years ago, tens of thousands of people are now living with cerebral palsy that might have been prevented.

15. NHS Evidence – provided by NICE We need to confront important uncertainties about the effects of treatment because otherwise: ● patients will be denied unrecognised beneficial care ● patients will be given unrecognised harmful care ● resources will be wasted on useless or unnecessarily expensive care

16. NHS Evidence – provided by NICE

18. Uncertainties from Patients, carers and clinicians - from today onwards; challenging Uncertainties from research recommendations – easy access, Cochrane Systematic Reviews, NICE Guidelines, journals. Uncertainties from ongoing research - no need to duplicate what is already happening

19. NHS Evidence – provided by NICE UK DUETs http://www.library.nhs.uk/duets