- between 20 and 40 years old
- have had 3 or more consecutive miscarriages and
- have had all the standard investigations without any problems being identified.
This is a randomised, double-blind, placebo-controlled trial – which is the “gold standard” for clinical research. Here’s what the terms mean:
Randomised There are two groups – treatment and non-treatment. Women taking part need to agree to be placed at random in either the treatment or non-treatment (placebo) group
Double-blind The women in the study won’t be told whether they are in the treatment or non-treatment group – and nor will their doctors.
Placebo-controlled The best way to compare the treatment and nontreatment groups is for them to have exactly the same conditions except the actual drug. This is done by giving the non-treatment group a placebo (dummy) tablet that looks exactly like the real treatment, but has no active ingredients.
You can also get information from the research team’s own website: www.prednisolonetrial.org.uk
The Prednisilone trialTaking part in the trial - what is involved. There are three main stages to the trial:
1. An endometrial biopsy, to screen for high levels of uNK cells (ordinary blood tests aren’t accurate). So far, around 40% of the women screened have been found to have raised uNK cell levels.
2. If you have high uNK levels, taking either Prednisolone or placebo (dummy) tablets daily for eight weeks when you become pregnant (you won’t know which tablets you are having). If you don’t have raised uNK levels, you won’t be eligible to continue in the trial. But you will have had the only reliable test for this possible cause of recurrent miscarriage.
3. Regular follow-up (which can be at your nearest early pregnancy unit and by telephone if you don’t live near Liverpool)
The M.A.’s Director, Ruth Bender Atik, is a member of the trial steering committee as a patient group representative. The group met in January and one of the things we discussed was the issue of taking part in a randomised trial. This is a topic that has come up several times on The M.A.’s message-board, so we thought we would share some of the issues here, especially as they are relevant to many other research trials.
Treatment vs placebo
As I’ve written elsewhere, the best way to check whether Prednisolone is helpful for women with raised uNK levels is to give some women the actual drug once they’re pregnant while others take a placebo, or "dummy" drug and then to compare the outcomes – pregnancy, birth and mother and baby’s health.
If women and/or their doctors know which they are taking, it is quite likely to make a difference to the outcome. Those knowing they are being treated tend to do better and so do people who think they are – it’s called the placebo effect. Doctors may treat women differently depending on which group they are in and this too could bias the results. So to try to be clear whether or not the actual drug makes a difference, women are assigned randomly to either the treatment or the placebo group and neither they nor their doctors know which they are taking.
All of them carry a card to say that they might be being treated with steroids – this is important in case they have side effects or any other illness or treatment.
They also all get exactly the same level of monitoring and care in their pregnancy. This is very important because other research studies have shown that access to regular scans, good care and support can improve outcomes, even without any treatment at all. That’s good news for anyone in the trial, whichever group they are in.
Most of the women screened so far have been prepared to be randomised, but others have doubts about being randomly assigned to either the treatment or the placebo group – usually because they have a clear idea of which group they want to be in.
Some are worried about the possible side-effects of steroid treatment. They are happy to help with the trial, but they are anxious about taking Prednisolone and want to be sure that they are in the non-treatment group.
Others are desperate to try a new treatment, even if it is unproven, and feel that they cannot cope with having just a 50% chance of having it. They may look for a different doctor or hospital where it can be prescribed.
All of these feelings are normal and understandable and the research team is acutely aware of how difficult this dilemma can be for some women. They care daily for women and couples with recurrent miscarriage and they certainly don’t want to make life more difficult or distressing for these patients. On the other hand, they want to find out whether steroid treatment really does increase the chances of a healthy pregnancy in women with raised uNK levels and this kind of randomised placebo-controlled trial is the best way to see whether it does or doesn’t. That could make a real difference in the future as either we will have a proven useful treatment for some recurrent miscarriage patients – or we will know that this treatment does not make any difference.
If you want more information or just to talk about it, do contact Ruth at The M.A.. You can also contact the research team via Dr Quenby’s secretary on 0151 702 4271.