Feasibility of a Chinese herbal clinical trial in the UK: The ORCHID study

Thank you to all involved in the ORCHID research study.  I set up this research study in January 2013 as part of my PhD research to explore the effects of Chinese herbal medicine for polycystic ovary syndrome.  A number of patients, members of the public and practitioners were invited to refer people onto the research study and I’m pleased to report that we had an enthusiastic response! 

I remain grateful to all who were involved in referring patients, emailing, tweeting, blogging, handing out flyers, printing out A4 signs for their local GP and CAM clinics and health food stores. 

The final publication has now been published in the BMJ Open and is accessible via the link below:

http://bmjopen.bmj.com/content/7/2/e011709

This journal is Open Access and enables patients, the public and healthcare professionals to access the science researchers produce and which I feel is vital for progress in science as well as in the Chinese medical profession.  I’ve summarised the key findings of the research study below:

Overview of the ORCHID research study results

What was this research trying to find out?

The ORCHID study was a feasibility and pilot study which involved offering a 6-month treatment course of Chinese herbal medicine (CHM) for women with irregular periods or no periods due to polycystic ovary syndrome (PCOS).   The main aim of this pilot research was to see whether women with PCOS were interested in taking herbs for their symptoms, whether herbs were acceptable for daily intake and whether the herbs led to improvements in symptoms.  These factors, amongst others, helped us to assess the feasibility of following up this research with a larger scale randomised clinical trial in the NHS. 

How was the study conducted?

The study looked at the effects of two different types of Chinese herbal medicine on PCOS symptoms in 40 women.  When women joined the study, a computer decided at random which treatment each woman would be taking.  Herbalists were blinded, meaning that they were unaware of which treatment participants were assigned to in order to make sure the treatment and care provided remained the same between the two groups.

The two types of Chinese herbal medicines were “Standardised” and “Individualised”.  All women were prescribed herbal granules to be reconstituted with hot water, and prescribed 8g twice per day (16g per day in total) for 6 months.

Although every woman on the study was assigned a herbalist who closely reviewed symptoms, women in the “Standardised” herbs group were given a fixed 14-herb combination of herbs that remained the same throughout the 6 month treatment course. The standardised formula was a modified version of Chai Hu Shu Gan San, the contents of which had been informed by a systematic review and a practitioner interview study that had been conducted before the trial started.  This allowed the standardised formula to be informed by evidence as well as by herbal practitioners. 

Women in the “Individualised” herbs group received an updated prescription after each visit which may be changed depending on how the herbalist felt the treatment was progressing. 

What were the overall conclusions from this study?

Our findings suggested this research is indeed feasible.  We had 40 places available for this research study and received almost 250 enquiries from women who were keen to participate.  All 40 spaces were filled within 7 months which was extremely encouraging as this part of clinical trials known as the ‘recruitment’ phase is one of the key issues in conducting clinical trials. 

Of the 40 women who took part, a small number of women reported difficulties with the taste of the herbs or with some side-effects such as skin breakouts or tiredness.  However, many were able to take the herbs and provide important data to our researchers throughout the 6 month treatment period.  This information suggests that women with PCOS are keen to use Chinese herbs for their symptoms and that running a clinical trial on a larger scale would indeed be possible. 

What did you find out about the effects of the herbs on women’s periods?

The results suggest that women in both standardised and individualised groups reported ‘statistically significant’ improvements in the regularity of their periods from baseline, meaning that by the end of the study the regularity of their periods was statistically significantly better after receiving treatment on the study. 

We measured menstrual response in two different ways.  One way was calculating a menstrual rate, defined as a menses every 28 days equating to a menstrual rate of 1 per month. This is in line with the methods used by other research studies in PCOS.  This means that a normal menstrual rate of 9-12 menstrual cycles a year equates to a menstrual rate of 0.75–1 per month, with oligomenorrhoea defined as 3-8 cycles per year equating to a menstrual rate of 0.25-0.67 per month, and amenorrhoea equating to a menstrual rate of <0.25 per month. 

At the start of the study, the standardised group had an average menstrual rate of 0.38 periods, meaning that they were getting approximately every 4-5 periods a year.  The individualised group had an average menstrual rate of 0.51 periods, meaning that they were getting approximately 6 periods a year.  By the end of the study, participants in the standardised group were reporting a menstrual rate of 0.62 equating to 7-8 periods a year and the individualised group were reporting a rate of 0.71, equating to 8-9 periods a year.    

Although participants in the individualised group experienced a slightly greater level of improvement in menstrual regularity, this was not ‘statistically significant’ from the participants in the standardised group, meaning that the difference between the two groups was not large enough for us to draw solid conclusions.  This was largely because this research study was small, involving only 40 women, and as such we were not expecting to see a significant difference between the two groups.  In order to find out whether a difference is evident, we would need to conduct a larger scale clinical trial and which the results from this current study suggest will now be possible.

We also analysed the menstrual rate by determining a response rate.  We defined a response as a change from amenorrhoea to either oligomenorrhoea or eumenorrhoea (normal menses), a change from oligomenorrhoea to eumenorrhoea, or as achieving pregnancy.  The standardised group’s response was 52.6% whilst the individualised group’s response was 72.3%.  Again this result was not statistically significant and whilst these results are encouraging, we still need larger studies and on an NHS population to be able to make more definitive conclusions.

We are also pleased to report that two of our participants became pregnant during the study and which resulted in the delivery of two healthy babies.

What other information about PCOS symptoms did the study gather?

In addition to menstrual data, we also collected information on safety and other PCOS symptoms such as excessive hair growth, weight and quality of life.  In terms of safety, liver and kidney function checks were largely normal and with no serious adverse reactions reported as a direct response to either of the two Chinese herbal treatments. 

For excessive hair growth, statistically significant improvements were seen in both treatment groups from the start of the treatment and by the end of the 6-month treatment period.  Although some women in the study reported losing significant amounts of weight, when the data was analysed as a group, there were no statistically significant differences in weight or body mass index - likely because not everyone who joined the study who joined the study experienced weight issues.  However, our waist hip ratio data suggests significant improvements were seen but only for the individualised treatment group. 

Women in both treatment groups reported significant improvements in quality of life, meaning that PCOS symptoms were overall seen to be much less burdensome in everyday life. 

Although this information suggests that Chinese herbs shows promise for various PCOS symptoms, these are early results that will need to be supported with further robust scientific research.

What are the main advantages and drawbacks of this research?

A key advantage is that we were able to conduct a 6-month study with women with PCOS and that we were able to collection health-related information from the beginning of the study.  However, this was a feasibility and pilot study which typically includes a small number of participants in order to see if trial processes – such as recruitment - are feasible.  This means that information from the outcome measures such as menstrual regularity or hair growth needs to be interpreted cautiously since we didn’t recruit enough people to say for sure whether herbs are helpful or not for these symptoms.  The results we report, although promising, therefore need to be considered preliminary and that it does not at this stage prove that one treatment is better than the other.

This was a pragmatic study looking at ‘real-world’ interventions that a woman with PCOS would be facing – in this case comparing a standardised or an individualised herbal approach.  This is an advantage because this design means that we are comparing the differences between two treatments that patients are able to choose from.  However, a key drawback of this research is that we were unable to include other conventional ‘real-world’ interventions as a comparison.  This means that our study doesn’t provide healthcare professionals like GPs and nurses with information on whether either of these approaches is more or less effective than a treatment that’s already available on the NHS.  The next challenge will be to include a group like this in a future study which would test Chinese herbal medicines against a treatment already offered on the NHS such as metformin.

What happens next?

The results of this study are now available in BMJ Open through the following link: 

http://bmjopen.bmj.com/content/7/2/e011709

Ongoing research

We are delighted to say that we have recently been successful in an NIHR grant application to build on this research further and which will be a step towards a larger definitive main study.  We will be conducting a follow-up clinical study in herbal practices in PCOS that we hope to be recruiting for in June 2017.  We hope to keep you updated along the way so please do stay tuned as we would love to see the same support again as we did for the ORCHID study – if not more!

Special Thanks

All participants and all women who enquired about the study

There were many who helped to support the ORCHID study in various ways and I’d like in particular to thank:

George He, David Hewitt and all at Phoenix Medical; Trevor Wing and team at the Women’s Natural Health Practice; ATCM (Kaicun Zhao); BAcC (Mark Bovey); CNHC (Hazel Russo); LSBU (Nicola Robinson and Ian Appleyard); Middlesex University (Mingzhao Cheng, Jidong Wu); RCHM (Nick Lampert, Emma Farrant and the REC team); University of Westminster (Volker Scheid, Felicity Moir); JCM (Peter Deadman, Daniel Maxwell); Avicenna (Mazin Al-Khafaji); Hanya Chlala; Martin Logue; Alex Owen; Jane Johnson; Christine Kim; Sing Sing Yu; Naava Carman; Zhihua Gao; Liqin Zhao; Jill Glover; Dan Jiang; Margella Salmins; Laurie Ayres; Pippa Hancock; Sarah George; Zak Han; Carly Day; Sarah May; Elizabeth Finch.