1. Changing with Herbs: a pilot randomised controlled trial of Western Herbal Practice
Julia Green
Department of Life Sciences
University of Westminster
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

2. Aim in this presentation
Example from research study of herbal practice for treatment of menopause illustrating:
Pragmatic RCT
Nested qualitative study – patient perspective
Mapping and describing practice
Practitioner- researcher perspective
Where next?
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

3. What is herbal medicine? (process)
While the plants themselves form the medicinal product used, herbal medicine is also a health care discipline, enacted as a PROCESS
Consists of relationships based on knowledge, skills and practices based on the theories, beliefs and experiences of the discipline
Best practices include assessment of an individual producing a tailored treatment plan to benefit the healthcare of the individual- so person centred.
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

4. Consultation: a very complex intervention …
treatment by a herbal practitioner is holistic
Lots of listening
full clinical history, physical examination, diagnosis
discuss nutrition, exercise, emotions etc
personal care plan
individual prescription, 5-9 herbs in the medicine, dispensed by the herbalist
6 appointments over 5 months individually tailored, holistic course of treatment
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

5. Why ask- Is herbal practice effective in treating menopausal symptoms?
Menopause: permanent end of menstruation, average age 51
80% women have symptoms at menopause (average 4 years)
22% of these found it a problem. In 10% can last 12 years.
Association between reduced quality of life and incidence of menopausal symptoms which may include:
Hot flushes
Night sweats
Palpitations
Insomnia
Depression
Vaginal dryness
Loss of libido
Memory and concentration problems
Menopausal symptoms common reason for consulting herbal practitioners
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

6. What research is there of herbal treatment of the menopause
What research is there of herbal treatment of the menopause? Quality variable so difficult to draw conclusions
Feb 2017 PubMed search- 10 years from 2007 – 2017 human clinical trials 250 hits
221 English language
87 after filter of title and abstracts
18 systematic reviews
16 studies on Soy/ isoflavones/ phytoestrogens
10 Black cohosh Cimicifuga racemosa
6 Red Clover Trifolium pratense
5 Rhubarb Rheum palmatum
4 Pueraria mirifica
3 Maca Lepidium meyenii
3 flax Linum usitatissimum
2 pine – pycnogenol
7 polypharmacy formulations (including within them black cohosh, hypericum, soy, vitex, clover, valerian, melissa).
1 trial each was found of 12 individual herbs: St John’s wort, hops, sage, liquorice, turmeric, epimedium, sea buckthorn, fennel, bryophyllum, sophorae, evening primrose oil, ginseng
21 of Asian medicine traditions or herbs (Chinese, Japanese, Taiwanese)
1 of pragmatic herbal practice.
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

7. Aims-
To assess the effectiveness of treatment of menopausal symptoms by qualified herbal practitioners
To develop methodology to assess effectiveness of professional herbal practice
Methods-
Prospective
Pragmatic (in the real world)
Randomised
Controlled (waiting list)
Pilot study
Aims and methods
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

8. The study design Population:
45 women aged from 1 GP practice in the UK “experiencing menopausal problems”
Intervention:
n = 15 usual care from herbal practitioner (6 appointments over 5 months individually tailored, holistic course of treatment )
Control:
n = 30 waiting list control (offered treatment after 4 months)
Outcome:
Primary outcome Greene Climacteric Scale
Secondary outcome MYMOP2
Green, J., Denham, A., Ingram, J., Hawkey, S., Greenwood, R., (2007) Treatment of menopausal symptoms by qualified herbal practitioners: a prospective, randomized controlled trial. Family Practice 24(5):
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

9. Flowchart of participants through trial
Assessed for eligibility
Women aged on neither HRT nor oral contraceptives identified by database search (n=252)
Replies to letters (n=161)
Enrollment
Excluded (n=116)
Not meeting inclusion criteria (n=116)
Of these still menstruating (n=82, other exclusion criteria (n=34)
Refused to participate (n= 0)
Other reasons (n= 0)
Women recruits block randomised (n=45)
Allocated to treatment by 3 herbal practitioners (n=15)
Received allocated intervention (n=14)
Did not receive allocated intervention (n= 1)
Complications of previous operation
Allocated to waiting list control (n= 30)
Received allocated intervention (n= 30)
Did not receive allocated intervention (n= 0)
Allocation
Lost to follow-up (n= 0)
Discontinued intervention (n= 0)
Lost to follow-up (n=1)
Moved away without valid forwarding address before completing timepoint 4 outcomes measures. Data up to then included.
Discontinued intervention (n=0)
Follow-Up
Analyzed (n=14)
Excluded from analysis (n= 0)
Analysis
Analyzed (n=30)
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

10. Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

11. …Questions and concerns…
Could we get ethical approval and funding?
Would we manage to recruit enough participants?
Would they be prepared to wait to give a control group?
Would it work?
Would the 2 outcomes measures agree?
Would the RCT agree with the cross over?
How many would drop out (retention)?
Would they attend consultations and take herbs and advice (compliance)?
Would we get published (dissemination)?
“goes on forever…endlessly problematic…like the menopause”
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

12. …Women found the waiting-list trial acceptable…
Treatment Group (n=15)
14 completed (all completed all questionnaires)
1 dropped out at beginning (6 operations, MRSA)
Control Group (n=30)
30 completed control phase
28 completed all questionnaires
size was fixed because of earlier concerns about high dropout making it impossible to estimate the sample size for larger trial
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

13. Psychological sub-scale comprises anxiety and depression sub-scales
Greene Climacteric Scores for those receiving herbal treatment and on waiting list at entry and time point 5 (24 weeks)
Psychological sub-scale comprises anxiety and depression sub-scales
Group
Treated
Time 1
N=14
Time 5
Untreated
N=30
P value
Greene Climacteric Scale
Mean
Std. Deviation
Std Deviation
Total
20.57
9.86
9.29
7.11
22.34
10.22
19.62
10.32
<0.001
psychological
11.57
6.54
5.71
5.73
12.00
5.68
10.07
0.019
anxiety
5.93
3.89
2.93
2.70
6.50
3.38
5.77
3.50
0.012
depression
5.64
3.41
2.79
3.19
5.50
3.08
4.30
3.66
0.272
somatic
4.07
3.10
1.36
0.74
4.38
4.77
4.22
0.131
vasomotor
3.29
1.64
1.29
1.20
3.00
1.88
2.97
1.59
libido
1.15
0.93
1.00
1.52
1.09
0.99
0.005
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

14. Total Greene scores over time for the treated and control groups
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

15. Results
The treatment group demonstrated a statistically and clinically significant reduction in menopausal symptoms compared to the control group
In the group receiving herbal treatment
Total scores for menopausal symptoms were reduced (p=0.001)
vasomotor scores reduced (p=0.001)
(vasomotor = hot flushes + night sweats)
libido increased (p=0.005)
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

16. MYMOP2 allows participants to select the symptoms that bother them most.
26 participants named hot flushes or night sweats (vasomotor symptoms) on a 7 point Likert scale 0-6).
For the treatment group these reduced, for the controls there was no significant difference
Time point
Treated mean (SD) (n=9)
P value
Control mean (SD) (n=17)
Baseline (entry)
4.11 (1.27)
0.015
3.71 (1.36)
0.71
Time point 5
(24 weeks)
1.78 (1.30)
3.41 (1.46)
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

17. The women on the waiting list control group were offered treatment by a herbal practitioner after 4 months What happened to them?
Clinical trials define a difference of 7 to13 points in the Greene climacteric scale as clinically useful. mean change in the treatment group (base/week 24) reduction of 10.3 points (RCT) (CI ) p<0.001 mean change in delayed group (waiting-list control group) (week 16/week 40) reduction of 8.6 points (X over) (CI ) p=0.012 So this cross over also showed herbalist’s treatments to be effective
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

18. 12 month data point: change from end of treatment to 12 months
immediate treatment group
reduction of 2.45 points (CI ) p=0.334
delayed group
reduction of 0.1 points (CI ) p=0.969
I.e Improvements were sustained after the course of treatment - which could have cost implications in economic analysis
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

19. Did women feel herbal treatment helped their menopausal symptoms
Did women feel herbal treatment helped their menopausal symptoms? Verbatim quotes From interviews with the treatment group
“Mainly it helped relieved the symptoms”
“When I’d been on the herbal medicine for a short time, the really bad flushes went They‘ve always been manageable since. I didn’t ever sweat again”
“I still get the odd flush not nearly as bad as I was having”
“Over the time I saw her there wasn’t a dramatic change”
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

20. Did women feel herbal treatment helped other symptoms?
“they decreased” (migraines)
“I got stiff muscles: that seems to be much better now”
“My cholesterol was very high and it’s come down naturally which is good”
“My confidence has come back since”
“(Headaches) are not hanging around for days like they used to”
“I was definitely aware of the herbs altering some of that mood” (depression)
“The joint pain definitely just went. It raised my energy”
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

21. Changing behaviour
“Things like soya milk, soya yoghurts that sort of thing as sort of phyto-oestrogen which is supposed to sort of help perhaps replace some of the oestrogen you lose (I think its oestrogen) and also things like seeds, sunflower and pumpkin seeds”
“And supplementing it with the fish oils and diet”
“I’m using more pulses and seeds”
“A greatly reduced fat diet, fat content, and my cholesterol was very high and it’s come down naturally which is good”
“drinking nettle tea”
“I only ever wear cotton, and then I layer: so that I can always take off a layer, and also exercising, how good that is and so I walk…everywhere all the time and made a special effort and I’ve joined a gym, some of my friends go to the gym so I do that as it’s social, and I swim twice a week that sort of thing so I've kept going”
“I was smoking at the time … and I gave up smoking in the end but it took a long time to get there”
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

22. Therapeutic relationship
“One of the most important things is the connection with that other human being. And that that has such a strong impact, umm to feel supported, to feel that, to give you confidence that you can help to heal yourself”
“You felt that going there she was trying to get to the root of the problem, you felt like you wouldn’t be fobbed off”
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

23. Holistic nature of consultation
“the whole holistic approach does take you a really by surprise, especially if you haven’t thought about it… and I certainly hadn’t…completely opposite to the NHS model really um and not feeling hurried and I suppose feeling that you were actually kind of quite important really”
“The holistic approach to looking at you as a human being. Looking at you as your whole body”
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

24. Negative Feedback Taste of herbal medicines
“They were disgusting, absolutely dreadful”
“but what was that? A small thing to pay! Down it goes”
“The only thing I would be saying now if I was going to go now is it costs a lot of money – its expensive and if you can’t afford it, it’s a bit difficult”
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

25. Which herbs were used? The answer is complex!
This methodology did not test specific herbs (efficacy)
It tested herbal practice (effectiveness)
This is discussed more fully in:
Denham A Green JR and Hawkey S (2011). What’s in the bottle? Prescriptions formulated by medical herbalists in a clinical trial of treatment during the menopause. Journal of Herbal Medicine 1 (3-4) doi: /jherbmed
Began to unpick the component parts but herbal practice needs more exploration and mapping

26. …up to 6 prescriptions were analysed for 35 women…
average 4 different prescriptions/woman
average 6 herbs per prescription (4 - 9)
80 herbs used (for range of conditions)
minimum estimate of herbs for future studies
the three practitioners trained together and prescribed similarly
Beginning to map the intervention
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

27. …favourite herbs… Herb No. of prescriptions (Total=145) %
Leonurus cardiaca, Motherwort
Cimicifuga racemosa, Black Cohosh
Salvia officinalis, Sage
Glycyrrhiza glabra, Liquorice
Rad. Taraxacum officinale, Dandelion
Trifolium pratense, Red Clover
Rumex crispus, Yellow Dock
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

28. Conclusions
Treatment by herbal practitioners in this case is effective.
Reduced overall menopausal symptoms particularly hot flushes and night sweats, and increased interest in sex.
Improvement maintained 1 year after treatment finished.
Women valued the whole experience.
Treatment (including herbs) was complex
Pragmatic RCT can evaluate holistic practice
More research needed on each level to describe practice and evaluate individual and synergistic components defining the therapy, mapping use, patient perspective, component effect, safety…
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

29. ...research team…
Thanks to the participants, to the herbal practitioners, to the Spence Group Practice, Bristol, Caroline Beatty and funders: National Institute of Medical Herbalists, NIMH Education Fund (charity no: ) Research sponsor University of Central Lancashire For nested qualitative study Avon Primary Care Research Collaborative Trial coordinator: Dr Julia Green, FNIMH Senior Lecturer, University of Westminster Alison Denham, FNIMH, Senior Lecturer in Herbal Medicine, University of Central Lancashire Rosemary Greenwood, Research and Development Support Unit, United Bristol Healthcare Trust Sue Hawkey, FNIMH, Lecturer in Herbal Medicine, University of East London Dr Jennifer Ingram, Research and Development Support Unit, United Bristol Healthcare Trust
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

30. Thank you for listening…
…Questions?
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH

31. References and reading
Denham A Green JR and Hawkey S (2001). What’s in the bottle? Prescriptions formulated by medical herbalists in a clinical trial of treatment during the menopause. Journal of Herbal Medicine 1(3-4) Green, J., Denham, A., Ingram, J., Hawkey, S., Greenwood, R., (2007) Treatment of menopausal symptoms by qualified herbal practitioners: a prospective, randomized controlled trial. Family Practice 24(5): Greene, J. (1998) Constructing a standard climacteric scale. Maturitas Greenhalgh, T (2006) How to Read a Paper: The basics of evidence-based medicine third edition London; BMJ books; Blackwell publishing A shorter version is available as an open-access article in the British Medical Journal (BMJ) at Ipsos Mori (2008) Public perceptions of herbal medicines (On-line) UK: Available from: rsl.com/researchpublications/researcharchive/2307/ Little, C. (2009) Simply because it works better: exploring motives for the use of medical herbalism in contemporary U.K. health care. Complementary therapies in medicine. 17, (5-6) Nice (2015) guidelines NG23 Paterson, C. (1996). Measuring outcomes in primary care: a patient generated measure, MYMOP, compared with the SF-36 health survey. Bmj, 312(7037), Williams, R. E., Levine, K. B., Kalilani, L., Lewis, J., & Clark, R. V. (2009). Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life. Maturitas, 62(2), All images copywrite Julia Green
Changing with Herbs: a pilot pragmatic RCT of Western Herbal Practice. Julia Green BSc PhD FNIMH