SIFT

1. SIFT • Study overview and • SIFT-specific GCP A multi-centre randomised controlled trial of two speeds of daily increment of milk feeding in very preterm or very low birth weight infants

2. Why do research (esp trials) • Need more answers! • E.g. ward round conundrums Cochrane Neonatal Group

3. Why bother? Neonatal Mortality Rate per 1,000 live births, England and Wales 1921 - 2003

4. Why bother? Stillbirth and neonatal mortality rates; United Kingdom: 2000-2009

5. An obligation to take part • 8,000 < 32 weeks per year in UK • approx 20% die and 11% of survivors are moderately or severely disabled (2006) Mangham et al Pediatrics 2009

6. An obligation to take part • 8,000 < 32 weeks per year in UK • approx20% die and 11% of survivors are moderately or severely disabled (2006) Mangham et al Pediatrics 2009

7. 880 disabled & 1600 deaths / year in UK

8. Sepsis and NEC on the up! Deaths in 24-31 weeks gestation infants Northern Region

11. Percentage cause of death n=671 n=473 n=360

12. Evidence linking sepsis & poor development JAMA, November 17, 2004—Vol 292, No. 19 6093 infants Born in 1993-2001 401 to 1000g

13. Jon Dorling 2010

14. Leaf A , Dorling J, Kempley S at al. Pediatrics. 2012;129:e1260–8.

15. Fast (30 ml/kg/day) vslow (18 ml/kg/day) increase in milk feed volumes • on survival without moderate or severe disability at 24 months CGA • For very preterm (<32 weeks) or VLBW infants

16. What is the current evidence? Updated Dec 2012

17. Studies to date • 5 studies, total of 588 infants

18. Slow v faster rates of feed advancement

19. Comparison of mortality 20 / 14 /

20. Comparison of NEC rates 16 / 16 /

21. Comparison of sepsis 20 / 14 /

24. Designed to fully answer important questions • HTA (rightly) pushed us to increase our power n = 2500 • Must therefore recruit babies to multiple studies to succeed

25. Power calculation 1 • primary comp = proportion of infants surviving without moderate or severe disability at 24 months of age corrected for prematurity. • estimate 80% survival to two years • estimate proportion surviving without moderate or severe disability in the slow group will be 69%

26. Power calculation 2 • 2,500 infants (1,250 per arm) will give 90% power to detect an absolute difference in proportions (two-sided 5% significance) of: • 5.7% for survival without moderate or severe disability • 69.0% in control group -> 74.7% • 5.4% in incidence of sepsis, and an absolute risk • 25.0% in control group -> 19.6% • 3.5% in the incidence of NEC (Bell stage 2 or 3) • from 6% in control group -> 9.5%)

28. Where are we at now? • Global R&D check approved • Site specific approvals to take place (<30 days) • NPEU will complete SSI forms but need information from you • PI contracts • Advertising nurse role

29. GCP training package • Includes following slides • Adapted from Intrapartum CSG toolkit • Training to enable staff to take consent and participate

30. Good Clinical Practice (GCP) • These are the fundamental standards that underpin all clinical research to ensure the: • safety and integrity of research participants • quality of the data • This study must be conducted in compliance with the protocol which has been approved by the Research Ethics Committee and the R&D dept. • Handout of the 14 principles of GCP. Further training & information available: http://www.crncc.nihr.ac.uk/training/courses/gcp

31. GCP: your responsibilities • Everyone involved in research has responsibility to ensure the safety and wellbeing of research participants • You must have suitable training and experience to perform the research tasks delegated to you • It is your professional responsibility to follow GCP standards, keep to the protocol and complete the required data collection forms (or inform your study midwife / PI if you are unable to do so)

32. Quick questions! • Who can take informed consent for the SIFT study? • Should all parents be approached on the neonatal unit? • Who should you contact about safety reporting?

33. What is informed consent? • A process by which a participant/parent voluntarilyconfirms their willingness to participate in a research study after having being informed of all aspects of the study that are relevant to their decision to participate. • It should only be obtained if the individual has been informed about what the study entails and of any potential benefits and risks of taking part • Informed consent must be documented by means of a written, signed and dated consent form

34. 6 point checklist

35. 6 point checklist

36. The consent form • Ensure the parent initials each box and does not tick them

37. The consent form • Ensure the parent initials each box and does not tick them • Both the cliniciantaking consent and the parentmust print their name, sign, and date the form

38. The consent form • Ensure the parent initials each box and does not tick them • Both the cliniciantaking consent and the parentmust print their name, sign, and date the form • 1 copy to SIFT Coordinating Centre; 1 copy to Parent; 1 copy to SIFT Data Collection File; 1 copy to infant’s notes

39. NPEU Clinical Trials Unit Department of Public Health University of Oxford Old Road Campus Oxford OX3 7LF T: 01865 617 919 F: 01865 289 740 E: sift@npeu.ox.ac.uk www.npeu.ox.ac.uk/sift Thanks for your attention Best of luck with the study!