From evidence to Policy:

1. From evidence to Policy: Paediatric guideline development inKenya Mercy Mulaku

2. Outline • Hierarchy of clinical evidence • GRADE system • Evidence to recommendations • Kenyan Experience

3. Hierarchy of clinical evidence High Systematic reviews Randomised controlled trials Observational studies Clinical experience Low Quality of evidence: the extent to which one can be confident that an estimate of effect or association is correct

4. Traditional way of formulating guidelines • Based on expert opinion

5. 3. Variable capacity to implement the new standard

6. What is GRADE? • Grading of Recommendations; Assessment, Development, and Evaluation.

7. Who uses GRADE?

8. Certainty of evidence GRADE system – a robust system for: • Assessing the certainty of evidence • How confident are we that the research is correct? • Moving from evidence to making recommendations • Consider other factors: balance of benefits and harms, feasibility, costs, values and preferences Grading of Recommendation, Assessment, Development and Evaluation

9. Levels of quality of evidence

10. Components determining quality • Randomised controlled trials start high • Observational studies start low What lowers certainty of evidence? 5 factors: Methodological limitations Inconsistency of results Indirectness of evidence Imprecision of results Publication bias

11. Linking evidence to recommendations • Research evidence alone never sufficient to make a clinical decision • Evidence + Judgement recommendations • Balance of benefits, risks – to patients, staff? • Costs? • Feasibility? • Acceptability, preferences – to patients, staff?

12. Approach to developing Kenyan National Guidelines (1) • Topic identification • Informal process • Systematic review • Contextualised SR and narrative • GRADE summary of findings tables • Panels provided with SR and key publications 4 weeks before the panel meeting

13. Guideline Panel Meeting, April 2013 • Three multidisciplinary panel (N~~20) • Policymakers, topic experts, researchers, clinicians • Guideline methodologists, external observers • Panels invited by Ministry of Health (MoH) & KPA 12 weeks before event and tasks explained

14. Summarised evidence • 2 systematic reviews and 8 randomised controlled trials; • Moderate to high quality evidence indicate that cord cleansing with 4% chlorhexidine may reduce the risk of neonatal mortality and sepsis in low-resource settings

15. Evidence to recommendation • Chlorhexidine for cord care: For hospital births (gestation >28 weeks, birth weight >1000 g) • Apply 4% active Chlorhexidine to the umbilical cord immediately after birth and thereafter daily till the cord separates; • Recommendation based on moderate quality evidence

16. Summarised evidence • 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports; • Hydroxyurea may improve morbidity and haematological outcomes in childhood sickle cell disease and appears safe in settings able to provide consistent haematological monitoring

17. Evidence to recommendation • Hydroxyurea should be considered for use in children below 5 years with severe form of sickle cell disease where minimum monitoring conditions and appropriate formulation are available; • Recommendation based on low quality of evidence

18. Summarised evidence • 6 studies were included (2 RCTs, 4 observational studies); • Only one study was from a low-income country (FEAST 2011 trial, N=3141 children); • This large study provides robust evidence that in low-income settings fluid boluses increase mortality in children with severe febrile illness and impaired circulation

19. Evidence to recommendation • In children with severe febrile illness and impaired circulation without signs of severely impaired circulation maintain hydration with appropriate maintenance fluids • Do not give a rapid fluid bolus; • Recommendation based on high quality evidence

20. Acknowledgement Prof. Mike English Prof. Paul Garner Dr. Dave Sinclair