LT: Welcome to this MRC podcast, I'm Laure Thomas and I'm here with Sarah Kenyon leading investigator on the Children's Oracle study. This was a long term follow up of the Oracle trial conducted in the mid to late 90s; the follow up study found some interesting results and I'm here to discuss with Sarah how she reacted when these results first came out.First of all Sarah, can you tell us a little bit more about the Oracle trial? SK: This was a trial looking at women in premature labour and looking at two specific groups in premature labour. First of all those with broken waters and secondly those with threatened early labour without broken waters. The evidence suggested that there might be sub clinical infection present, so the Oracle trial evaluated the use of two antiobiotics, Co-amoxyclav and Arithromicin. The results which were published in The Lancet in 2001 show that for women with broken waters we found improvements in neonatal morbidity with the prescription of Arithromicin. So clinical practice is now that Arithromicin is given. For women with spontaneous pre-term labour and intact membranes, the Oracle trial found no evidence of either harm or benefit with a prescription of antibiotics.The children's study was a follow up at seven years old of those children and we use a structured parental questionnaire and were lucky enough to be able to collect key stage one. We found some very unexpected and surprising results.
LT: Can you tell us a little bit more about what you did find?
SK: Broken waters first of all, having had the anticipation of benefit at discharge from hospital, we were hoping to see and expecting to see benefit at seven, but we found no differences between the groups. Antibiotics were of no benefit at seven years, no harm either, but no benefit at seven years. Unexpectedly for women with spontaneous pre-term labour and intact membranes, we found evidence of harm, of cause for concern. We found increases in function impairment, mainly mild, in women who took any Arithromicin, that's either with or without Co-amoxyclav and we found increases in the numbers of babies with cerebral palsy with the prescription of either antibiotic. LT: What does that mean about the use of antibiotics in pregnancy?
SK: I think it's very important that a couple of messages come across. The first one is that this is not routine treatment for these women, these women had no evidence of infection when they were recruited. Practice today does not involve the prescription of antibiotics to women with spontaneous pre-term labour with intact membranes and the very important public health message is that women who have clinical infection should be treated with antibiotics.
LT: And when did you first get a sense that you weren't going to get the results you were hoping for, but something else was unfolding here? SK: Towards the end of last year when we did the first set of data analysis we realised that we were looking at something that was very unexpected. What we did is call a group of experts together, we as co-applicants, well we loss of expertise, we didn't have what was necessary so we called an expert group together which involved international participation and we opened the results up for discussion, which was hugely helpful to us. After that the commission on human medicines also reviewed the analysis and the findings.
LT: So when you say the commission for human medicines reviewed this, this means that you must have informed the Department of Health of the preliminary findings?
SK: Yeah, this was done by the MRC. We immediately contacted the funders, the MRC and we've worked together over the last nine months really to bring this to fruition in a organised and thought through way. LT: Because it's very difficult isn't it, to make sure that the messages that come out of this study are clear and that there isn't a panic created around the use of antibiotics in other circumstances in pregnancy? SK: I think that's absolutely the top message, but for me the other one was to make sure that the participants in the study had the results before they were published in The Lancet or wherever they were published and that's what we've done. The people who took part, the women who took part in the study have had the results a couple of days before publication in The Lancet and there's a helpline been set up for them to talk through any of their concerns. LT: And you did quite a lot of work didn't you, on how best to communicate these results to participants? Because it's very difficult when you have such complex findings. SK: It's been harder than writing the Lancet papers, writing the results leaflets for participants. We worked very hard with Professor Mary Dixonwards from the University of Leicester, there was a qualitative researcher in her team, they ran a series of focus groups completely unaware of the results with our participants, so we could first of all talk about the language we might use in the leaflet and also get the results as clear as is possible for participants.
LT: It's always gutting in a sense isn't it, when you were hoping to find a benefit from a procedure, to find something different. How personally, how have you felt about this research?
SK: I suppose my objective has been to do the research as well as possible. It would have been really good for the women, if the treatment had been beneficial, but unfortunately it wasn't and the most important thing was to get the evidence into the public domain. While that's been a very uncomfortable process on occasion, that was clearly the most responsible thing to do. So personally how I felt – proud and pleased because we've done a very good study and well maybe in the next couple of days we'll know but I hope we've managed it in such a way that it doesn't cause unnecessary alarm or concern. LT: Sarah Kenyon, thank you very much.
LT: Laure Thomas SK: Sarah Kenyon
