INIS Collaborators’s Meeting PSANZ 4 April 2006

Total 117 centres Total 2272 babies Well done, thank you for your hard work!  Because the event rate is higher than originally planned, the UK MRC have revised the target sample size from 5,000 to 4,000 to preserve power to show a 14% Relative Risk Reduction.  MRC have also awarded an extra year’s funding

INIS TRIAL UPDATE MEETING AGENDA Websites [google: inis ctc] Websites [google: inis ctc] Current recruitment and follow up Current recruitment and follow up MRC funding extension till June 2007 MRC funding extension till June 2007 Revised sample size ~ 4,000 Revised sample size ~ 4,000 Recommencement of European/ Argentinean sites Recommencement of European/ Argentinean sites Neonatal sepsis, inflammation and anti- inflammatory therapies Neonatal sepsis, inflammation and anti- inflammatory therapies Video consent study Video consent study  Any Other Business

inis website [Google] inis ctc

Australian recruitment 2006 Grand totalJanFebMar Canberra 8811 RPA Women and Babies 31 2 Royal North Shore 43 2 Westmead John Hunter, Newcastle Liverpool Royal Hospital for Women Nepean 233 Children's Hospital at Westmead 4 Monash Medical Centre 863 Royal Women's, Melbourne Mercy Hospital for Women Royal Children's, Melbourne 42 4 Royal Women's, Brisbane 15 Flinders Medical Centre 6 Women's and Children's 9 1 Royal Hobart 26 2 Totals

New Zealand recruitment 2006 Grand totalJanFebMar National Women's Christchurch Women's Dunedin 1951 Middlemore 23 Palmerston North Waikato 22 3 Wellington Women's Totals

TOTAL RECRUITMENT ANZ = 1071 in 24 centres

Total centres and babies worldwide  ANZ 24 Total babies 1071 UK 64 Total babies 1120 Denmark 3 Belgium 1 Eire 2 Serbia 1 Greece 1 Argentina 21 Total babies 81 Total centres: 117 Total babies: 2272

 Recruitment was temporarily suspended in UK, Europe and Argentina in Jan 2006  Until compliance with new documentation requirements for good manufacturing practice  Not because of any safety issue with the Scottish IVIG product

 Recruitment recommenced 24 March in UK, Europe and Argentina  Argentina have 21 centres Estimated contribution of 50 babies per month Estimated contribution of 50 babies per month

1 year follow up  Important to maintain contact with families at 1 year to maximize the 2 year follow up rate  490 babies have reached 1 year corrected for gestation  452 babies have complete data  37 have data pending  1 is presumed lost to follow up

2 year Follow up  ANZ sites  205 babies surviving babies have reached 2 years corrected for gestation  Currently 180 (88%) have complete data  24 have appointments pending  1 is lost (? Moved to Samoa)  Expected rate of 2 year follow up is 99%

MRC extension funding application  UK MRC has funded an extra year’s funding for UK/ European and Australian sites.  This will extend recruitment in Australia until mid or late 2007

Revised sample size % primary outcome in control group % primary outcome in treatment group Relative risk reduction (%) Total sample size , , ,848

Neonatal sepsis, inflammation and anti-inflammatory therapies  Neonatal inflammation is an important determinant of white matter damage  IVIG has multiple immuno-modulatory properties  IVIG is an important candidate as an anti- inflammatory therapy in neonatal sepsis

Reviews of the evidence that perinatal inflammation predisposes to neonatal brain damage  Inflammation and preterm birth John Newnham John Newnham  Inflammation and the developing human brain Don Peebles Don Peebles  Antenatal inflammation: consequences for neonatal immunology Alan Jobe Alan Jobe

Can a 500 g baby mount an “over- inflammatory” response? Can a 500 g baby mount an “over- inflammatory” response?

 INIS is addressing a major research question  Does IVIG reduce mortality and morbidity in infants with suspected or proven neonatal infection? 

A CONSENT DVD DESIGNED TO IMPROVE CONSENT UPTAKE TO RANDOMISED CONTROLLED TRIALS IN NEONATOLOGY: A PILOT STUDY IN THE INIS NETWORK Priya Duggal-Beri, Phyllis Butow, Wendy Hague, Val Gebski, Lorraine O’Regan, William Tarnow-Mordi; on behalf of the International Neonatal Immunotherapy Study (INIS) Collaborative Group.

Barriers to participation in randomised controlled trials: a systematic review. Ross et al 1999 Clinician barriers included: Clinician barriers included: time constraintstime constraints lack of staff and traininglack of staff and training worry about the impact on the doctor- patient relationshipworry about the impact on the doctor- patient relationship concern for patientsconcern for patients loss of professional autonomyloss of professional autonomy difficulty with the consent proceduredifficulty with the consent procedure lack of rewards and recognitionlack of rewards and recognition insufficiently interesting question.insufficiently interesting question.

Patient barriers included: Patient barriers included: additional demands of the trialadditional demands of the trial patient preferencespatient preferences worry caused by uncertaintyworry caused by uncertainty concerns about information and consent.concerns about information and consent.

 There is no evidence on the impact of Digital Video Decoders (DVDs) or videos on knowledge or confidence of staff in obtaining consent, and on uptake of consent by parents.  We explored the effectiveness of a DVD/ video and accompanying booklet in 24 INIS sites in describing consent delivery methods describing consent delivery methods improving knowledge about the INIS trial. improving knowledge about the INIS trial.

VINIS: Video/ DVD + Booklet site intervention study  A pilot RCT in 24 ANZ INIS sites to explore whether a video and booklet for staff who seek consent can improve their knowledge and confidence whether a video and booklet for staff who seek consent can improve their knowledge and confidence its potential effect on recruitment rate. its potential effect on recruitment rate.  1645 Wednesday 5 th April  Level 2 Meeting Room 11

Data Collection issues  Excellent rate of completion and accuracy of CRFs  Consent forms Please ensure that all signatures by parents and investigators and witnesses are complete Please ensure that all signatures by parents and investigators and witnesses are complete  HIC consent forms Please remember to ask new and old parents to complete this consent form (for economic analysis) Please remember to ask new and old parents to complete this consent form (for economic analysis)  Days of respiratory support after INIS intervention Please include all days the baby received any respiratory support in your hospital Please include all days the baby received any respiratory support in your hospital