Description of current pediatric research agenda. Introduction to translational research.

1. Pediatric Research Current state, difficulties and promises F. Cachat 1,2 1 Pediatric Department, Samaritain Regional Hospital, Vevey, 2 Départment of pediatrics, Pediatric Nephrology Unit, University Hospital, Lausanne, Switzerland

3. Research question Clinical Answer Research staff Research Staff recruitment / retention / mentoring Clinical question formulation Targeted population Population study generalization / minorities Study type Limitations of studies / RCT Generalization of findings Implementations Guidelines formulation Clinical research methodology

5. Where and how is pediatric research performed / current state Increase in RCT in the USA but also in developing countries (India, China…)

6. Where and how is pediatric research performed / current state RCT in major vs. small research centers

9. Clinical question Answer Research staff Research Staff recruitment / retention / mentoring Clinical question formulation Targeted population Population study generalization / minorities Study type Limitations of studies / RCT Generalization of findings Implementations Guidelines formulation Clinical research methodology Determinant of research Potential difficulties

11. Current limitations: research faculty

13. Solution: training in research / better mentoring Mentee or Protégé Mentor

14. Clinical question Answer Research staff Research Staff recruitment / retention / mentoring Clinical question formulation Targeted population Population study generalization / minorities Study type Limitations of studies / RCT Generalization of findings Implementations Guidelines formulation Clinical research methodology

15. Research settings / targeted population Population with condition X Study population Conclusions 1 2 1. Is the study population representative of the general population? Internal and external validity of the study 2. Are the conclusions of the study applicable to the general population? Implementation of the findings to the general population / translational research

18. Research settings / targeted population

19. Is the population representative of my patients? Is the research standart adequate?

22. Clinical question Answer Research staff Research Staff recruitment / retention / mentoring Clinical question formulation Targeted population Population study generalization / minorities Study types Limitations of studies / RCT Clinical research methodology Generalization of findings Implementations Guidelines formulation

24. RCT long-term results

25. RCT long-term results

26. Current limitation: long-term studies Treatment Placebo Treatment vs. placebo Surveillance Years (/decades) Outcome Years (/decades) RCT long-term results

27. Solution: cohort studies systematic reviews / meta-analysis RCT Cohort studies RCT long-term results

28. RCT long-term results

29. RCT long-term results

30. RCT conflicting results

31. RCT conflicting results

32. Solution: cohort studies systematic reviews / meta-analysis RCT conflicting results / meta-analysis

33. New treatment against what? Rejection of H0 One tailed test 10% Response rate 30% Response rate Small number of subjects RCT against placebo

34. RCT best available treatment

35. New treatment against what? Rejection of H0 One tailed test Non inferiority trials Equivalence trials 30% Response rate 35% Response rate Sample size considerable larger than placebo-controlled trials RCT best available treatment

36. Equivalence, non-inferiority and superiority trials Superiority trial Non inferiority trial

37. Equivalence, non-inferiority and superiority trials

38. Clinical question Answer Research staff Research Staff recruitment / retention / mentoring Clinical question formulation Targeted population Population study generalization / minorities Study types Limitations of studies / RCT Clinical research methodology Generalization of findings Implementations Guidelines formulation

39. Basic research Biomarkers (PSA, CRP…) Individual patient Community Clinical trials Evidence (Guidelines…) Translational Research Type I Translational Research Type II