Fiona Denison publishes on the NIHR blog

Image

You can read Fiona's NIHR blog entry entitled ‘How can a group sequential design help improve the delivery of a placenta’ via this link, or refer to the copy below:

https://www.nihr.ac.uk/blogs/how-can-a-group-sequential-design-help-improve-the-delivery-of-a-placenta/8359

How can a group sequential design help improve the delivery of a placenta?

Author: Dr Fiona Denison, Reader/Honorary Consultant in Maternal and Fetal Health, MRC Centre for Reproductive Health, University of Edinburgh

The period of time immediately following the birth of a baby is very special for both mother and baby.  This unique time allows bonding to be initiated and is also an ideal time to establish breastfeeding.

However, not all women are able enjoy this as, following the birth of their baby, some experience the problem of a retained placenta. This is when the placenta remains undelivered after the birth of a baby. A retained placenta affects approximately one in 50 women who have a vaginal delivery in the UK.  Untreated, it can result in major uterine bleeding, and is therefore potentially a life-threatening condition.  Currently, women with a retained placenta need to have an operation in theatre where the placenta is manually removed under an anaesthetic. At present, there is no effective alternative medical treatment for retained placenta, which avoids the need for an operation. 

We were very grateful to receive funding from the NIHR to allow us to undertake a large clinical trial in labour wards within several UK hospitals to evaluate an alternative medical treatment for women who sustain a retained placenta.

Our trial, known as the GOT-IT Trial, was designed to study the clinical and cost effectiveness of the treatment glyceryl trinitrate spray (GTN) in women who develop a retained placenta following the birth of their baby.  GTN spray is a drug that relaxes muscles and is more widely known for relieving symptoms of angina in patients with coronary artery disease.

The GOT-IT Trial is a randomised double blind trial comparing two puffs of glyceryl trinitrate spray with a placebo.  Both the GTN and the placebo were packaged in an identical format and both deliver the study medication as a spray under the tongue (sublingual). Neither the women taking the study treatment, nor the midwives and clinicians caring for them, knew whether participants were receiving GTN or placebo.  Over 1,100 women have been enrolled to the trial.

Group sequential design

The trial was designed using a group sequential design approach.  This design was chosen because it was uncertain how many women who were eligible for the trial would actually go on and require surgery to remove the placenta.  This uncertainty was due to a lack of data being available to detail the effect of GTN resulting in delivery of the placenta.

A group sequential design was ideal for this trial as it allowed the maximum number of subjects to be enrolled, therefore providing sufficient power.  At the same time, this approach also provided the Data Monitoring Committee several opportunities to confidentially examine the data throughout the trial. The Data Monitoring Committee could advise stopping the trial early if there was evidence of futility or alternatively if there was an overwhelming, convincing treatment effect. Thus, using a group sequential design provided the most cost effective design for a trial such as GOT-IT.  

The trial had an initial pilot phase incorporated into the main design of the trial to allow the practicalities of the trial to be examined and tested before proceeding to the main trial.  Qualitative research, led by Professor Julia Lawton, was embedded within the internal pilot. This research obtained views of women who had participated in the trial and clinical staff who had recruited them to help identify any potential issues. This information was fed-back to the trial team and used to optimise the consent and recruitment pathways for the main trial.

Our trial finished recruiting ahead of schedule. The preliminary results have now been presented at the British Maternal and Fetal Medicine Society Conference (BMFMS) 2018 and will be followed by a publication later this year. Visit the NIHR Journals Library for more details.

Dr Fiona Denison, Reader/Honorary Consultant in Maternal and Fetal Health, MRC Centre for Reproductive Health, University of Edinburgh

Chief Investigator: A pragmatic group sequential placebo controlled randomised trial to determine the effectiveness of Glyceryl trinitrate for retained placenta (GOT-IT-Trial)