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omplementary Therapies in Medicine (2015) 23, 430—438

Available online at www.sciencedirect.com

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eveloping clinical practice guidelines forhinese herbal treatment of polycysticvary syndrome: A mixed-methods modifiedelphi study

ily Lai ∗,1, Andrew Flower1, Michael Moore1, George Lewith1

niversity of Southampton, Primary Care and Population Sciences, Aldermoor Health Centre,ldermoor Close, Southampton, Hampshire SO16 5ST, United Kingdomvailable online 14 March 2015

KEYWORDSChinese herbalmedicine;Polycystic ovarysyndrome;Menstrual disorders;Delphi;Mixed methods

SummaryObjectives: Preliminary evidence suggests Chinese herbal medicine (CHM) could be a viabletreatment option for polycystic ovary syndrome (PCOS). Prior to conducting a clinical trial itis important to consider the characteristics of good clinical practice. This study aims to useprofessional consensus to establish good clinical practice guidelines for the CHM treatment ofPCOS.Design and setting: CHM practitioners participated in a mixed-methods modified Delphi studyinvolving three rounds of structured group communication. Round 1 involved qualitative inter-views with practitioners to generate statements regarding good clinical practice. In round 2,these statements were distributed online to the same practitioners to rate their agreement usinga 7-point Likert scale, where group consensus was defined as a median rating of ≥5. Statementsreaching consensus were accepted for consideration onto the guideline whilst those not reach-ing consensus were re-distributed for consideration in round 3. Statements presented in theguidelines were graded from A (strong consensus) to D (no consensus) determined by medianscore and interquartile range.Results: 11 CHM practitioners in the UK were recruited. After three Delphi rounds, 91 statementitems in total had been considered, of which 89 (97.8%) reached consensus and 2 (2.2%) didnot. The concluding set of guidelines consists of 85 items representing key features of CHM

prescribing for PCOS. Conclusions: These guidelines can be viewed as an initial framework that captures fundamental principles of good clinical pract© 2015 Elsevier Ltd. All rights re

∗ Corresponding author. Tel.: +44 02380 241073; fax: +44 02390 701 12E-mail addresses: L.Y.W.Lai@southampton.ac.uk (L. Lai), flower.powe

L3@southampton.ac.uk (G. Lewith).1 Fax: +44 02390 701 125.

ttp://dx.doi.org/10.1016/j.ctim.2015.03.003965-2299/© 2015 Elsevier Ltd. All rights reserved.

ice for CHM.served.

5.r@which.net (A. Flower), mvm198@southampton.ac.uk (M. Moore),

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Developing clinical practice guidelines for Chinese herbal tr

Introduction

Polycystic ovary syndrome (PCOS) affects 6—18% of womenof reproductive age and is a heterogeneous conditioncharacterised by endocrine and metabolic disturbances.1—3

Primary care management typically involves oral contra-ceptives and insulin-sensitising agents which have beenassociated with intolerable side-effects, poor adherenceand increased metabolic risk.4—8 This highlights issues withcurrent management and warrants exploration of othertreatments that could be more acceptable.

Chinese herbal medicine (CHM) is used for symptoms ofPCOS and there is emerging evidence from randomised con-trolled trials (RCTs) suggesting CHM could play an importantrole in the management of PCOS.9 However, many of theseRCTs have been conducted in China and are methodologicallypoor thus limiting the generalisability of these findings.10

This necessitates further exploration of the effects of CHMwith a fully-powered RCT in the UK. It is important howeverto ensure such a study is relevant to CHM practice in Westerncountries such as the UK, and that it takes into consider-ation characteristics of good clinical practice as determinedby CHM practitioners. Accordingly, the aim of this study wasto establish good clinical practice guidelines for the CHMtreatment of PCOS.

Materials and methods

Design

We conducted a practitioner-consultation exercise using amodified Delphi method. The Delphi structures group com-munication to enable the views of informed individuals tobe considered anonymously from each other and attemptsto minimise the drawbacks of collective decision-making. Itis particularly useful where diverse opinions exist and hasother advantages as reducing the effect of prevailing opin-ions or dominant individuals, and enabling participants toalter previously expressed opinions without fear of losingface.11 It is a formal consensus method recognised by theUK’s National Institute for Health and Clinical Excellence(NICE) for developing guidelines.12—14 It has also been suc-cessfully employed in a number of CHM and acupuncturestudies for generating consensus in clinical practice or pro-tocol development.15—19

Ethical approval was granted in June 2011 by the Univer-sity of Southampton School of Medicine ethics committee(SOMSEC094.11).

Recruitment

We estimated 15 practitioners would be required to gen-erate a sufficiently diverse range of views.16,18 Practitionershad to (1) have been in practice for a minimum of 4 years, (2)be a registered CHM practitioner in their respective country,(3) have self-reported expertise or interest in gynaecologi-

cal conditions such as PCOS, (4) have access to the internetand to email, and (5) be fluent in English. To foster diversityin opinion, we purposively sampled for gender, country ofCHM training, current country of practice and CHM practice

twot

ent of PCOS 431

tyle to include traditional Chinese medicine and classicaltyles of practice.

We used expert and snowball sampling methods by pro-iding CHM professional bodies in the UK, US, Australia andanada with a project brief, inviting suggestions of approx-

mately 10 suitable practitioners. When practitioners wereontacted, we asked for further suggestions of practitioners.

number of practitioners known to the research team werepproached directly. Practitioners were provided an invita-ion letter, participant information sheet and completed aonsent form prior to the study.

elphi rounds

he Delphi involves iterative rounds of structured groupommunication. Round 1 consists of an ‘idea-generating’xercise which typically involves participants independentlyroducing a list of ideas or statements. In this study however,he lead author conducted in-depth qualitative interviewsith each participant. This is a modification of the Delphiethod which has been successfully carried out in previous

tudies and which in our view would maximise participantnvolvement.18,20

Interviews were conducted using a semi-structured inter-iew guide which included open non-leading questions.nterviews were audio-recorded and transcribed verbatimy the lead author or an independent transcription service.ll transcriptions were checked by the lead author. Addi-ional field notes were taken and considered during analysis.nalysis was based on principles of thematic and frameworknalysis and conducted by coding in Microsoft Word 2010sing the ‘Comments’ function and charting in Microsoftxcel 2010. Framework analysis features a number of stages,nvolving familiarising self with the data, developing a the-atic framework and charting and mapping to identifyatterns within the data.21 This enabled a list of statementsegarding clinical practice to be prepared for the next Delphiound.

In round 2, these statements were distributed back tohe group using SurveyMonkey, a web-based questionnaire.articipants were asked to indicate their level of agreementith each statement using a 7-point Likert scale (‘1 stronglyisagree’ to ‘7 strongly agree’), including a score of ‘4 nei-her agree nor disagree’. We provided a response option ofnot applicable’ (NA) for each item and a free-text com-ents box. Where participants had chosen to respond ‘NA’

o a particular statement, they were removed as a denomi-ator in response to that item only. Demographic and clinicalackground information was also collected within this ques-ionnaire.

Statistical analysis was conducted using Microsoft Excel010. Group consensus was defined a priori as a medianroup rating of 5 or more as used in previous Delphi studies.18

ollowing the Delphi method, items achieving consensusere accepted. Items not achieving consensus were circu-

ated back to the participants for reconsideration in round 3.hese were presented with the participant’s original rating,

he group rating and an invitation to re-consider their ratinghich they could accept or decline. Where a new rating wasffered, this was used to reanalyse the group rating. Free-ext comments from round 2 were analysed qualitatively and

432 L. Lai et al.

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to reflect the levels of variability and therefore of opinionas demonstrated in earlier studies [14,23]. The criteria fordetermining grading were decided post hoc after statementshad been distributed and are shown in Table 1.

Table 1 Criteria for grading clinical guideline items.

Grade Description Median IQRa

A Strong consensus 6 OR 7 ≤2B Moderate consensus 6 OR 7 >2

5 ≤2

Figure 1 Overview

hich could lead to the generation of new statements to beistributed in round 3. We planned for each statement to beirculated a maximum of two times, and a maximum of fourelphi rounds to be conducted. An overview of the Delphirocess can be viewed in Fig. 1.

linical guidelines

e regarded it important to present clinical practice pointsegardless of consensus status, and to illustrate consensustrength. We followed NICE guidance that grades strength

f recommendation using the system Grading of Recommen-ations Assessment, Development and Evaluation (GRADE)22]. The grading we adopted took into consideration theedian ratings per item, and the interquartile ranges (IQRs)

the Delphi process.

C Weak consensus 5 >2D Consensus not achieved <5

a IQR = Interquartile range.

Developing clinical practice guidelines for Chinese herbal treatm

Table 2 Demographics and characteristics of recruitedparticipants.

Characteristics Number of participants (%)

GenderMale 5 (45.5)Female 6 (54.5)

CHM practice styleTCM only 7 (63.6)Classical only 1 (9.1)Both TCM and Classical 3 (27.3)

Country of herbal trainingUK 7 (63.6)China 4 (36.4)

Number of years in practice (mean = 18, range 4—34,SD = 9.99)

4—10 3 (27.3)11—20 5 (45.5)21—30 1 (9.1)31—40 2 (18.2)

Number of PCOS patients per month0 0 (0)1—4 6 (54.5)5—10 4 (36.4)11—20 0 (0)

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Results

Recruitment

From 47 potentially eligible practitioners, 11 (23.4%) wererecruited. Fig. 2 shows the recruitment flowchart.

Demographics of the 11 participants are shown in Table 2.All participants were currently practicing in the UK as prac-titioners from Australia, US and Canada either did notrespond, or declined to participate for reasons such as alack of time and not feeling sufficiently experienced. Owingto lack of time and resources, we were unable to pur-sue recruitment in these countries. However, as shown inTable 2, we recruited a heterogeneous group of UK practi-tioners that was comparable to those from these countriesin terms of training, CHM practice style, years in practiceand experience [24—26].

Delphi rounds

For round 1, 10 face-to-face interviews and 1 tele-phone interview were conducted with a mean duration of56 minutes (39—70 minutes). As these 11 interviews provideda sufficiently diverse range of opinions which was suitablefor refinement within the Delphi process, no further inter-views were required.

Qualitative analysis resulted in the generation of 85statements covering 6 themes: Clinical presentation (11

items), Chinese medicine diagnosis (12 items), Chinesemedicine treatment strategy (4 items), Chinese medicineinterventions planning (16 items), Chinese herbal interven-tion planning (17 items) and Treatment assessment and

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ent of PCOS 433

valuation (25 items). Fig. 3 shows how a statement wasenerated from interview data.

In round 2, a questionnaire containing these 85 state-ents were distributed back to the 11 participants,

chieving a 100% response rate within 8 weeks. Group con-ensus was achieved in 83 items (97.6%) whilst 2 items (2.4%)ailed to reach consensus. Comments were made in 13 ofhe 16 free text boxes by at least one participant and weredded to the initial data corpus for further analysis. ‘NA’ was

response for 1 item and for one participant only and whoas subsequently removed as a denominator in the analysisf this item.

In round 3, a questionnaire was distributed containing 8tems; 2 items that had failed to reach consensus, 4 newtems generated from free-text responses and 2 clarifiedtems. The 2 clarified items originated from 1 item thateached group consensus in round 2 but which had receivedomments regarding lack of clarity. We decided this shoulde separated into 2 new items for consideration. This ques-ionnaire achieved 100% response within 3 weeks. For one ofhe two re-distributed items, 5 participants chose to re-ratehe item. Analysis taking into consideration the new ratingsndicated group consensus was not achieved. For the seconde-distributed item, all 11 participants declined the offer tohange their ratings. No further redistribution of these twotems was therefore required. For the four new items andwo clarified items, group consensus was achieved.

In summary after three Delphi rounds comprising onenterview round and two questionnaire rounds over 7onths, a total number of 91 unique statement items hadeen distributed for consideration by the panel, of which 8997.8%) reached consensus and 2 (2.2%) did not.

uideline presentation

rom the 91 unique statement items, 83 were presented inhe guideline. To improve clarity, two items were combinedo form one item in the guideline. One item was discardeds it had been replaced with two new items. Six items wereiscarded to avoid repetition.

The concluding set of guidelines consists of 85 items: 83uideline items presented with a grade indicating strengthf group consensus and two clinical practice items reportingosage ranges that were not graded as consensus had noteen sought. Fig. 4 shows a section of the guidelines ‘Chi-ese Herbal Intervention Planning’. The complete guidelinean be seen in Appendix 1.

iscussion

his study adopted a modified Delphi approach to facilitate systematic and rigorous practitioner-consultation exerciseith 11 UK CHM practitioners, resulting in the developmentf good clinical practice guidelines. These guidelines con-ist of 85 items illustrating key features of CHM-prescribingor PCOS, 83 of which have been assigned a consensusrade. These describe PCOS symptoms and signs seen in

linical practice, common CM diagnoses and practice pointsegarding how treatment is managed and evaluated by CHMractitioners. These clinical perspectives can now be com-ared with other published work and used to inform future

434 L. Lai et al.

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tudies. For example the RCT interventions described in aochrane review for PCOS-related subfertility focused oniagnostic patterns of Kidney yang deficiency and Spleen Qieficiency.10 Although these were reported in our guidelines,ther patterns were also identified such as Excess Cold inhe Uterus and Blood deficiency that were not reported inhe RCTs. This may be because these patterns occur morerequently in oligo- and amenorrhoea than in subfertility orecause these patterns do not occur sufficiently frequentlyn the PCOS population to warrant investigation in RCTs. Weope this demonstrates how clinical knowledge drawn fromhe Delphi exercise can be triangulated and compared withurrent evidence as a way of maximising model validity.

A strength of this study is the use of a mixed-methodspproach. The content of our guidelines had been generated

hrough qualitative interviews, instead of basing items solelyn published research or the research team’s experience.his ensured guideline items were generated inductivelynd grounded in real-world practice by CHM practitioners

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ecruitment process.

ndependent from the research team. A further strength wasur 100% response rate. Dropout between rounds is a widelycknowledged criticism of Delphi studies and although qual-tative interviews have been used in previous studies,18,27

e feel our decision to conduct in-depth interviews with allarticipants contributed greatly to participant retention andhich strengthens the credibility of this study. Finally, we

ecruited a heterogenous group of practitioners with criteriaetermined a priori. This enabled us to consider the views of

diverse group of practitioners and thus maximise the rele-ance of our findings across CHM practice in the West. Of par-icular note is the diversity of CHM practice styles within ouranel to represent the range of styles found in other coun-ries, rather than focusing only on the dominant TCM style.

Owing to language restrictions and a lack of resources,

e required practitioners to be fluent in English whicheans the views of those fluent only in Chinese may not

ave been adequately represented. However, we includedhe purposive sampling criterion ‘country of CHM training’

Developing clinical practice guidelines for Chinese herbal treatment of PCOS 435

Figure 3 Generation of a statement from interview data.

PCOS=Polycystic ovary syndrome; Consensus grade: A = Strong consensus; B = Good consensus; C = Weak consensus;D = No consensus, NA=Not Applicable, formal consensus not sought

Figure 4 Excerpt ‘Chinese Herbal Intervention Planning’ from concluding clinical guidelines.

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nd successfully recruited four bilingual practitioners whoad trained and practiced in China. We deemed this to beufficient representation for the purpose of this study. Weere also unsuccessful in recruiting from a range of West-rn countries as intended due to limited time and resources.espite this, we successfully recruited a heterogenous groupf UK practitioners whose characteristics were comparableo those in other Western countries and thus we feel areepresentative of Western CHM practice.24—26 Researchersishing to recruit overseas practitioners in future studiesould benefit from allowing more time and flexibility duringhe recruitment process. We would also advise researcherso cost-in modest reimbursement for practitioner-time as andditional way of maximising recruitment.

To our knowledge, this is the first time the Delphi methodas been successfully used to present good clinical practiceuidelines relating to real-world CHM-prescribing for PCOS.nique to this Delphi study is the presentation of consen-us grading within our guidelines which provides a clear andccessible set of statements. We chose to adopt this in thepirit of NICE guideline development standards which assesshe strength of recommendations using GRADE and seek toonvey information in a transparent manner.22 Our aim waso use a similarly simple grading system to maximise the rel-vance and applicability of our guidelines to clinical practicend research. By ensuring that research evidence is based oneal-world clinical practice, these guidelines form the firsttep towards maximising model validity in CHM research.his also promotes transparency as it enables researcherso justify decisions regarding study design and readers toritique research based on clinical perspectives that haveeen drawn out prior to a study commencing. These guide-ines should not be seen as a definitive checklist but rathers an initial mapping exercise of key practice points in CHM-rescribing. In the absence of population-level data fromlinical and CHM prescription records and the paucity of CHMtudies conducted in Western populations, these guidelinesemain an important step towards documenting an initialramework of best practice.

onclusions

e have successfully used a modified Delphi approacho facilitate a systematic and rigorous practitioner-onsultation exercise, resulting in the development of goodlinical practice guidelines for CHM treatment of PCOS.hese guidelines were used in a subsequent clinical trials the basis for good practice within the study protocol28

nd can be viewed as an initial framework for good clinicalractice to be updated as necessary. They provide a suf-ciently broad scope to capture fundamental principles ofood clinical practice whilst being appropriately detailedo be useful for practitioners and researchers alike.

inancial support

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onflict of interest

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L. Lai et al.

cknowledgements

his study is supported by a PhD research training fellow-hip awarded to the main author by the National Instituteor Health Research (NIHR) School for Primary Care ResearchSPCR) (RCS Ref 10-0894). The NIHR SPCR is a partner-hip between the Universities of Birmingham, Bristol, Keele,anchester, Nottingham, Oxford, Southampton and Univer-

ity College London. The views expressed are those of theuthors and not necessarily those of the NHS, the NIHR orhe Department of Health.

We are grateful to the practitioners who generouslyonated their time and insight during this research study:aurie Ayres, Naava Carman, Jennie Dallas, Zhihua Gao, Jilllover, Dan Jiang, Martin Logue, Alex Owen, Trevor Wing,idong Wu and Liqin Zhao. Other than the role stated, thoseamed have had no other contribution to the study design,nalysis or writing of the protocol and of this report.

ppendix 1. Good clinical practice guidelinesor the treatment of polycystic ovaryyndrome with Chinese herbal medicine

his clinical guideline has been developed by researcherst the University of Southampton using a practitioner-onsultation exercise following the Delphi method. Thisuideline describes key features of good clinical practicehat were developed with a panel of 11 herbalists practic-ng in the UK on the topic of Chinese herbal medicine (CHM)rescribing for polycystic ovary syndrome (PCOS).

For clinical practice items where consensus has beenought, these have been graded as follows:

A = Strong consensus; B = Good consensus; C = Weak con-ensus; D = No consensus

For clinical practice items where formal consensus wasot sought and which describe a range of opinions, theseave been summarised and graded ‘NA’.

Chinese medicine (CM) here includes acupuncture, Chi-ese herbal medicine, moxibustion and tuina.

linical practice items Consensus

. Clinical presentation

.1 In the clinic, patients with PCOS presentwith one or more of the following signs andsymptoms:1.1.1. Delayed periods (cycles longer than35 days)

A

1.1.2. Absent periods (no period for 6months or more)

A

1.1.3. Infertility A1.1.4. Acne A1.1.5. Hirsutism (excessive facial and bodyhair)

A

1.1.6. Pre-menstrual syndrome (PMS) A1.1.7. Emotional issues A1.1.8. Weight management issues A1.1.9. Heavy periods B1.1.10. Painful periods C

.2. PCOS is diagnosed as a result of fertilityinvestigations

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Developing clinical practice guidelines for Chinese herbal tr

2. Chinese medicine diagnosis2.1. Treatments in Chinese medicine are based

on pattern differentiationA

2.2. In PCOS, combined excess and deficiencypatterns are found

A

2.3. In PCOS, knowledge of a patient’sbiomedical status, such as status of ovariesor testosterone levels, informs the Chinesemedicine treatment

A

2.4. The following excess patterns are found inPCOS:2.4.1. Phlegm Damp accumulation A2.4.2. Blood stasis A2.4.3. Liver Qi stagnation A2.4.4. Excess Cold in the Uterus A2.4.5. Stagnated Liver Heat A2.5. The following deficiency patterns arefound in PCOS:2.5.1. Kidney Yang deficiency A2.5.2. Spleen Qi deficiency A2.5.3. Spleen Yang deficiency A2.5.4. Blood deficiency B2.5.5. Kidney Yin deficiency C

3. Chinese medicine treatment strategy3.1. Chinese medicine is an integrated system

of interventions and self-care measurestailored to the individual

A

3.2. With combined excess and deficiencypatterns in PCOS, Chinese medicinetreatments should address bothsimultaneously

A

3.3. In PCOS, when excess patterns start toclear, treatments should prioritise nourishingdeficiencies

A

3.4. In PCOS, treatments should initiallyprioritise clearing excess patterns

D

4. Chinese medicine interventions planning4.1 When providing Chinese medicine

treatment for PCOS, one or more of thefollowing are recommended:4.1.1. Chinese herbs A4.1.2. Acupuncture A4.1.3. Stress management techniques A4.1.4. Dietary changes A4.1.5. Appropriate work-life balance A4.1.6. Advice on exercise A

4.2 Chinese herbs have the followingadvantages over acupuncture:4.2.1 More effective for chronic conditions A4.2.2 More effective for severe patterns ofdeficiency

A

4.2.3 Have a longer-lasting effect A4.2.4 More effective for hormonal conditions A4.2.5. More effective for severe patterns ofexcess

A

4.2.6. Can be administered more readily on A

a daily basis

4.3. Acupuncture has the following advantagesover Chinese herbs:4.3.1. Provides rapid relief of pain A

ent of PCOS 437

4.3.2. Moves Qi rapidly A4.3.3. More effective for emotional issues B4.3.4. Provides direction for Qi B

.4. In PCOS, CHM only i.e. withoutacupuncture is effective

A

.5. In PCOS, both acupuncture and CHM arenecessary to provide effective treatment

B

.6. In PCOS, acupuncture only i.e. withoutCHM is effective

D

Chinese herbal intervention planning.1. Decoctions are more effective thanconcentrated powders

A

.2. Concentrated powders are suitablyeffective for PCOS

A

.3. Individualised herbs are more effectivethan standardised herbs

A

.4. Individualisation is important:

.4.1. To adapt to the specific needs of thepatient

A

.4.2. To prevent resistance to a herbalprescription

C

.5. In Blood stasis, herbs for removing Bloodstasis should be prescribed for use duringmenses

A

.6. Whilst patients are actively trying toconceive:

.6.1 Blood stasis removing herbs should notbe prescribed after ovulation

B

.6.2 It is suitable to prescribe Blood stasisremoving herbs after ovulation, IF patientsalso present with a Blood stasis condition

A

.7. The prescribed daily dosage range ofconcentrated powders is 5 g to 25 g

NA

.8. The most frequently prescribed dailydosage range of concentrated powders is 5 gto 15 g.

NA

Treatment assessment and evaluation.1. Chinese herbs are effective for thefollowing PCOS-related symptoms:6.1.1. Delayed periods (cycles longer than35 days)

A

6.1.2. Infertility A6.1.3. Absent periods (no period for 6months or more)

A

6.1.4. Heavy periods A6.1.5. Pre-menstrual syndrome (PMS) A6.1.6. Acne A6.1.7. Hirsutism (excessive facial and bodyhair)

A

6.1.8. Painful periods A6.1.9. Emotional issues A6.1.10. Weight management issues B

.2. In PCOS, initial response to Chinese herbsis determined by assessing one or more ofthe following:6.2.1. Cycle lengths A

6.2.2. Heaviness of menstrual flow A6.2.3. Duration of menstrual bleeding A6.2.4. Menstrual clotting A6.2.5. Period pain A

4

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1

1

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2

2

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6.2.6. Colour of menstrual blood A6.2.7. Pulse palpation A6.2.8. Basal body temperature chart A6.2.9. Emotional wellbeing B6.2.10. Abdominal palpation B6.2.11. Tongue appearance B

.3. Response to Chinese herbs is slower in:6.3.1. Phlegm Damp accumulation conditions A6.3.2. Overweight patients B6.3.3. Blood stasis conditions D

.4. When regulating menstruation in PCOS, aregular menstrual cycle is the observation ofthree consecutive menstrual cycles, each 35days or less in length

A

.5. In PCOS, an initial response to Chineseherbs is observed within 3 months

A

.6 When prescribing Chinese herbs fordelayed periods in PCOS (cycles longer than35 days), a regular menstrual cycle isobserved within 6 months

A

.7. When prescribing Chinese herbs for absentperiods in PCOS (no period for 6 months ormore), a regular menstrual cycle is observedwithin 9 months

A

eferences

1. Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale. HF. A prospective study of the prevalence of thepolycystic ovary syndrome in unselected Caucasian women fromSpain. J Clin Endocrinol Metab 2000;85(7):2434—8.

2. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, DaviesMJ. The prevalence of polycystic ovary syndrome in a commu-nity sample assessed under contrasting diagnostic criteria. HumReprod 2010;25(2):544—51.

3. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005;352(12):1223—36.

4. Sills ES, Perloe M, Tucker MJ, Kaplan CR, Genton MG, SchattmanGL. Diagnostic and treatment characteristics of polycystic ovarysyndrome: descriptive measurements of patient perception andawareness from 657 confidential self-reports. BMC WomensHealth 2001;1(1):3.

5. Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N. Ovar-ian function and metabolic factors in women with oligomen-orrhea treated with metformin in a randomized double blindplacebo-controlled trial. J Clin Endocrinol Metab 2002;87(2):569—74.

6. Donnan PT, MacDonald TM, Morris AD. Adherence to prescribedoral hypoglycaemic medication in a population of patients withType 2 diabetes: a retrospective cohort study. Diabet Med2002;19(4):279—84.

7. Grant RW, Devita NG, Singer DE, Meigs JB. Polypharmacy andmedication adherence in patients with type 2 diabetes. Dia-betes Care 2003;26(5):1408—12.

8. Legro RS, et al. Clomiphene, metformin, or both for infertility

in the polycystic ovary syndrome. N Engl J Med 2007;356(6):551—66.

9. Raja-Khan N, Stener-Victorin E, Wu X, Legro RS. The physio-logical basis of complementary and alternative medicines for

L. Lai et al.

polycystic ovary syndrome. Am J Physiol Endocrinol Metab2011;301(1):E1—10.

0. Zhang J, et al. Chinese herbal medicine for subfertile womenwith polycystic ovarian syndrome. Cochrane Database Syst Rev2010;9:CD007535.

1. von der Gracht HA. Consensus measurement in Delphi studies:review and implications for future quality assurance. TechnolForecast Soc Change 2012;79(8):1525—36.

2. Jones J, Hunter D. Consensus methods for medical and healthservices research. Br Med J 1995;311(7001):376—80.

3. National Institute for Health and Clinical Excellence. The guide-lines manual; 2009.

4. Linstone HA, Turoff M. In: Linstone HA, Turoff M, editors. TheDelphi method: techniques and applications. 2002.

5. Smith CA, Grant S, Lyttleton J, Cochrane S. Using a Delphiconsensus process to develop an acupuncture treatment proto-col by consensus for women undergoing Assisted ReproductiveTechnology (ART) treatment. BMC Complement Altern Med2012;12:88.

6. Alraek T, Borud E, White A. Selecting acupuncture treatment forhot flashes: a Delphi consensus compared with a clinical trial.J Altern Complement Med 2011;17(1):33—8.

7. Zhao J, Zha Q, Jiang M, Cao H, Lu A. Expert consensus onthe treatment of rheumatoid arthritis with Chinese patentmedicines. J Altern Complement Med 2013;19(2):111—8.

8. Flower A, Lewith GT, Little P. Seeking an oracle: using the Del-phi process to develop practice guidelines for the treatment ofendometriosis with Chinese herbal medicine. J Altern Comple-ment Med 2007;13(9):969—76.

9. Smith CA, Betts D. The practice of acupuncture and moxibus-tion to promote cephalic version for women with a breechpresentation: implications for clinical practice and research.Complement Ther Med 2014;22(1):75—80.

0. Hasson F, Keeney S, McKenna. H. Research guidelines for theDelphi survey technique. J Adv Nurs 2000;32(4):1008—15.

1. Ritchie J, Spencer L. Qualitative data analysis for applied pol-icy research. In: Bryman AB, Burgess RG, editors. Analyzingqualitative data. Routledge: Abingdon; 1994. p. 173—94.

2. Guyatt GH, et al. GRADE: an emerging consensus on rating qual-ity of evidence and strength of recommendations. Br Med J2008;336(7650):924—6.

3. Tan J, et al. Acne severity grading: determining essential clin-ical components and features using a Delphi consensus. J AmAcad Dermatol 2012;67(2):187—93.

4. Wang ZG. Job analysis report. National Certification Commis-sion for Acupuncture and Oriental Medicine; 2013.

5. Allied Health Workforce. A.I.o.H.a. Welfare. Editor 2012:Cam-berra.

6. Bensoussan A, Myers SP. Towards a safer choice: The practice oftraditional Chinese medicine in Australia. Campbelltown NSW:Faculty of Health, University of Western Sydney Macarthur;1996.

7. Cochrane S, Smith CA, Possamai-Inesedy. A. Developmentof a fertility acupuncture protocol: defining an acupuncturetreatment protocol to support and treat women experienc-ing conception delays. J Altern Complement Med 2011;17(4):329—37.

8. Lai L, Flower A, Moore M, Prescott P, Lewith G. Polycystic ovary

syndrome: a randomised feasibility and pilot study using ChineseHerbal medicine to explore Impact on Dysfunction (ORCHID)— Study protocol. European Journal of Integrative Medicine2014.