Electro-acupuncture versus Sham Electro-acupuncture versus Standard Care for Acute and ...

224 Pages·2014·4.37 MB·English

Electro-acupuncture versus Sham Electro-acupuncture
versus Standard Care for Acute and Delayed
Chemotherapy-Induced Nausea and Vomiting—A
Feasibility Pilot Study and Acupuncture Service Evaluation
in the Day Oncology Unit

Christopher Graham McKeon

A thesis submitted in fulfilment of the requirements for the
degree of Master of Science (Honours) Health Science

National Institute for Complementary Medicine,
School of Science and Health, University of Western Sydney

June, 2014
Declaration

I, Christopher Graham McKeon declare that this thesis, submitted in fulfilment of the
requirements of the award of Master of Science (Honours), in the National Institute
for Complementary Medicine, School of Science and Health, University of Western
Sydney, is wholly my work unless otherwise referenced or acknowledged. This
document has not been submitted, either wholly or in part, to any other educational
institution.

Signature: Date: 15th June 2014

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Acknowledgments

I wish to give my love and thanks to my lovely wife Danielle and two beautiful boys
Hamish and Callum, who have given me great support and tolerance as I have strived
to complete this research and particular to the boys and their lost afternoons playing
cricket and rugby because Dad was too busy writing. This thesis is dedicated to my
family who has been with me throughout this long journey.

To my supervisors, Professor Caroline Smith, Professor Esther Chang and Professor
Janet Hardy I thank you for your help, encouragement, patience and support during
this project. Particular thanks go to Caroline for her extreme patience, as I was
developing my academic writing skills. You collectively have helped me grow as a
person and a researcher, so I thank you. I would like to acknowledge and thank Elite
Editing, who edited my thesis, and editorial intervention was restricted to Standards
D and E of the Australian Standards for Editing Practice.

My thanks go to the Australian Acupuncture and Chinese Medicine Association and
the Mater Foundation for the funding to conduct the trial. My gratitude also goes to
the Mater Foundation and the Smiling for Smiddy Foundation for the funds to set up
the acupuncture service in the day oncology unit in the Mater Adult Hospital, being
the first one in Australia where the patients do not pay was an honour and pleasure.

To all my colleagues in the Mater day oncology unit, doctors, nurses, allied health
and administration staff thank you for the support and help to conduct this trial and
service evaluation I could not done it without your help.

And finally but definitely thank you to the wonderful patients who agreed to
participate and utilise the service.

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Contents
Declaration .................................................................................................................. ii
Acknowledgments ..................................................................................................... iii

Contents ..................................................................................................................... iv

List of Figures .......................................................................................................... viii

List of Tables ............................................................................................................. ix

List of Abbreviations ................................................................................................. x

Abstract ...................................................................................................................... xi

Chapter 1: Cancer Treatment Side Effects and Complementary Medicines ....... 1

1.1 Introduction ........................................................................................................ 1
1.2 Background ........................................................................................................ 2
1.3 Cancer ................................................................................................................ 2
1.4 Management of Cancer ...................................................................................... 3
1.4.1 Surgery ........................................................................................................ 3
1.4.2 Radiotherapy ............................................................................................... 4
1.4.3 Chemotherapy ............................................................................................. 4
1.5 Chemotherapy Adverse Effects .......................................................................... 6
1.6 Chemotherapy-Induced Nausea and Vomiting .................................................. 7
1.6.1 Mechanism of Chemotherapy-Induced Nausea and Vomiting ................... 9
1.6.2 Evidence-Based Research and Practice in Relation to Chemotherapy-
Induced Nausea and Vomiting ................................................................... 9
1.6.3 Use of Anti-Emetics in the Treatment of Chemotherapy-Induced
Nausea and Vomiting ............................................................................... 10
1.6.4 Treatment of Chemotherapy-Induced Nausea and Vomiting Using
Non-Pharmacological Interventions ......................................................... 11
1.7 Use of Complementary Medicine (Including Acupuncture) in Cancer Care ... 15
1.8 History and Definition of Acupuncture ............................................................ 16
1.9 The Practice of Acupuncture ............................................................................ 16
1.10 Rationales and Style of Acupuncture ............................................................. 17
1.11 Integrative Medicine ...................................................................................... 17
1.12 History of Integrative Oncology .................................................................... 18
1.13 Conclusion...................................................................................................... 21

Chapter 2: A Systematic Review of Acupuncture and/or Acupressure for

Chemotherapy-Induced Nausea and Vomiting ..................................................... 22
2.1 Introduction ...................................................................................................... 22
2.2 Background ...................................................................................................... 22
2.3 Methods ............................................................................................................ 23
2.3.1 Type of Studies ......................................................................................... 23
2.3.2 Participants ................................................................................................ 23
2.3.3 Type of Intervention to be Included .......................................................... 24
2.3.4 Types of Outcome Measures ..................................................................... 24
2.3.5 Search Strategy ......................................................................................... 24
2.4 Methods of the Review .................................................................................... 25
2.4.1 Study Selection ......................................................................................... 25
2.4.2 Data Extraction ......................................................................................... 25

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2.4.3 Assessment of Risk of Bias ....................................................................... 25
2.4.4 Measures of Treatment Effect ................................................................... 26
2.5 Systematic Review ........................................................................................... 26
2.6 Randomised Controlled Trials ......................................................................... 27
2.6.1 Excluded Studies ....................................................................................... 29
2.6.2 Excluded Reviews ..................................................................................... 29
2.7 Characteristics of the Studies ........................................................................... 29
2.8 Description of the Interventions ....................................................................... 30
2.9 Outcome Measures ........................................................................................... 31
2.10 Assessment of Risk of Bias in Acupuncture Trials ........................................ 31
2.10.1 Selection Bias .......................................................................................... 35
2.10.2 Attrition Bias ........................................................................................... 35
2.10.3 Performance Bias .................................................................................... 36
2.10.4 Measurement Bias ................................................................................... 36
2.11 Assessment of the Risk of Bias Acupressure Trials ....................................... 36
2.11.1 Selection Bias .......................................................................................... 36
2.11.2 Attrition Bias ........................................................................................... 37
2.11.3 Performance Bias .................................................................................... 37
2.11.4 Measurement Bias ................................................................................... 37
2.12 Meta-Analysis ................................................................................................ 37
2.12.1 Acupuncture plus Medication v. Medication Only ................................. 37
2.12.1.1 Frequency of Vomiting ..................................................................... 37
2.12.1.2 Dose of Rescue Medication .............................................................. 38
2.12.2 Acupuncture plus Medications v. Sham Acupuncture plus
Medications .............................................................................................. 38
2.12.2.1 Frequency of Vomiting ..................................................................... 38
2.12.2.2 Frequency of Nausea........................................................................ 38
2.12.2.3 Dose of Rescue Medication .............................................................. 38
2.12.2.4 Helpfulness of Acupuncture ............................................................. 38
2.12.3 Acupressure plus Medication v. Medication Only .................................. 38
2.12.3.1 Frequency of Vomiting ..................................................................... 38
2.12.3.2 Frequency of Nausea........................................................................ 39
2.12.4 Acupressure plus Medication v. Sham Acupressure plus Medication .... 39
2.12.4.1 Frequency of Vomiting ..................................................................... 39
2.12.4.2 Frequency of Nausea........................................................................ 39
2.12.4.3 Use of Rescue Medication ................................................................ 39
2.13 Discussion ...................................................................................................... 40
2.14 Agreements and Disagreements with Other Studies or Reviews ................... 43
2.15 Clinical Commentary ..................................................................................... 43
2.16 Conclusion...................................................................................................... 43

Chapter 3: Methodology .......................................................................................... 45

3.1 Methods ............................................................................................................ 45
3.1.1 Research Questions ................................................................................... 45
3.2 Study Design .................................................................................................... 46
3.2.1 Study Design Rationale ............................................................................. 46
3.3 Methodological Issues to Consider for Acupuncture Research ....................... 47
3.4 Study Participants............................................................................................. 48
3.5 Recruitment Strategy ........................................................................................ 48
3.6 Randomisation.................................................................................................. 49
3.7 Blinding ............................................................................................................ 50

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3.8 Treatments and Study Schedule and Intervention ............................................ 50
3.8.1 Treatment as Usual .................................................................................... 50
3.8.2 Electro-Acupuncture ................................................................................. 50
3.8.3 Control Arm: Sham Electro-Acupuncture ................................................ 52
3.9 Outcome Measures and Data Collection .......................................................... 53
3.9.1 Feasibility Endpoints ................................................................................. 53
3.9.2 Secondary Endpoints ................................................................................. 53
3.9.3 Data Collection ......................................................................................... 53
3.10 Data Collection Instruments ........................................................................... 54
3.10.1 Functional Living Index Emesis (FLIE) ................................................. 54
3.10.2 Patient Diary ........................................................................................... 55
3.10.3 Toxicity ................................................................................................... 55
3.10.4 Practitioner Therapeutic Interaction ........................................................ 57
3.10.5 Expectations ............................................................................................ 57
3.11 Sample Size .................................................................................................... 58
3.12 Data Analysis ................................................................................................. 58
3.13 Acupuncture Service Evaluation .................................................................... 59
3.14 Research Questions ........................................................................................ 60
3.15 Study Design .................................................................................................. 60
3.16 Study Participants........................................................................................... 60
3.16.1 Inclusion Criteria ..................................................................................... 61
3.16.2 Exclusion Criteria ................................................................................... 61
3.17 Ethics .............................................................................................................. 61
3.18 Study Administration ..................................................................................... 62
3.19 Acupuncture Service ...................................................................................... 62
3.20 Sampling ........................................................................................................ 63
3.21 Study Endpoints ............................................................................................. 63
3.22 Data Collection ............................................................................................... 63
3.23 Data Collection Instruments ........................................................................... 64
3.24 Safety.............................................................................................................. 64
3.25 Quality of Life and Wellbeing ....................................................................... 66
3.26 Data Analysis ................................................................................................. 67

Chapter 4: Pilot Study and Service Evaluation Results ....................................... 68

4.1 Results from the Pilot Randomised Controlled Trial of Electro-
Acupuncture for Chemotherapy-Induced Nausea And Vomiting .................... 68
4.2 Recruitment to the Trial ................................................................................... 69
4.2.1 Consort Statement ..................................................................................... 69
4.3 Demographics .................................................................................................. 71
4.3.1 Age ............................................................................................................ 71
4.3.2 Sex ............................................................................................................. 71
4.3.3 Diagnosis ................................................................................................... 71
4.3.4 Emetogenic Rating .................................................................................... 71
4.3.5 Compliance with Treatment Schedule Day 3 ........................................... 73
4.3.6 Loss and Drop Out From the Trial ............................................................ 73
4.3.7 Completion Rates of Outcome Measures .................................................. 73
4.3.8 Integrity of Blinding in the Study ............................................................. 75
4.4 Secondary Study Endpoints ............................................................................. 76
4.4.1 Functional Living Index Emesis Changes over Time and between
Groups ...................................................................................................... 76
4.4.2 Symptom: Vomiting Changes over Time and Between Groups ............... 78

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4.4.3 Symptoms of Nausea Changes over Time and Between Groups .............. 79
4.4.4 Use of Rescue Anti-Emetics ..................................................................... 79
4.4.5 Toxicity of Intervention ............................................................................ 80
4.4.6 Identification of a Washout Period During a Second Cycle of
Chemotherapy ........................................................................................... 82
4.4.7 The Influence of Participant Expectations of Benefit on Treatment
Outcomes .................................................................................................. 82
4.4.8 Effect of the Practitioner Therapeutic Encounter ..................................... 85
4.5 Results from the Acupuncture Service Evaluation .......................................... 86
4.6 Demographics of Participants .......................................................................... 86
4.6.1 Sex ............................................................................................................. 86
4.6.2 Age ............................................................................................................ 87
4.6.3 Diagnosis ................................................................................................... 87
4.7 Participant’s Feedback on Service and Complementary and Alternative
Medicine Use .................................................................................................... 87
4.8 Participants’ Perception of Benefit from the Service ....................................... 88
4.9 Adverse Events ................................................................................................. 89
4.10 Measure Yourself Concern and Wellness Concerns and Problems ............... 90
4.11 Measure Yourself Concern and Wellness Pre- and Post-Test Results ........... 91
4.12 Measure Yourself Concern and Wellness Concerns Qualitative Analysis .... 92
4.13 Measure Yourself Concern and Wellness: Other Concerns Affecting
Your Health ...................................................................................................... 94
4.14 Measure Yourself Concern and Wellness: Important Aspects of the
Service as Identified by Participants ................................................................ 94
4.15 How We Might Improve the Service ............................................................. 95
4.16 Other Feedback Provided by Respondent Comments .................................... 96
4.17 Discussion of Results ..................................................................................... 96
4.18 Discussion of Results Acupuncture Service Evaluation .............................. 102
4.19 Concluding Comments ................................................................................. 104

Chapter 5: Discussion ............................................................................................ 105

5.1 Systematic Review of Acupuncture to Reduce Chemotherapy-Induced
Nausea and Vomiting Key Findings............................................................... 105
5.2 Key Findings from the Feasibility Study ....................................................... 106
5.3 Key Findings from Acupuncture Service Evaluation. ................................... 108
5.4 Methodological Discussion ............................................................................ 108
5.5 Strengths of the Trial ...................................................................................... 109
5.6 Study Limitations ........................................................................................... 111
5.7 Future Research .............................................................................................. 113
5.8 Clinical Implications ...................................................................................... 115
5.9 Implications for Education ............................................................................. 116
5.10 Conclusion.................................................................................................... 117

References ............................................................................................................... 118

Appendices .............................................................................................................. 134

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List of Figures
Figure 2.1: Results from Search Strategy .................................................................. 28
Figure 4.1: Consort Diagram...................................................................................... 70

Figure 3.1 Sham Points Location ............................................................................. 209

viii
List of Tables
Table 1.1: Cancers Treated by Chemotherapy ............................................................. 5
Table 1.2: Emetogenicity of Chemotherapy Agents .................................................... 8

Table 1.3: Summary of Non-Pharmacological Intervention Trials ............................ 12

Table 2.1: Assessment of Bias ................................................................................... 32

Table 4.1: Demographics of Trial Participants .......................................................... 72

Table 4.2: Outcome Measures Completion Rates ...................................................... 74

Table 4.3: Blinding Integrity of Allocation................................................................ 75

Table 4.4: FLIE Outcomes by Study Group .............................................................. 77

Table 4.5: Vomiting by Study Group over Cycle 1 and 2 ......................................... 78

Table 4.6: Nausea by Study Group over Cycle 1 and 2 ............................................. 79

Table 4.7: Adverse Events over the Trial Period ....................................................... 80

Table 4.8: Expectations of Study Participants by Group ........................................... 84

Table 4.9: Therapeutic Encounter by Treatment Group ............................................ 85

Table 4.10: Demographics of Study Participants ....................................................... 87

Table 4.11: Participants’ Feedback about the Service ............................................... 88

Table 4.12: Participant’s Expectations of Benefit from Acupuncture ....................... 89

Table 4.13: AEs Of Patients Using the Acupuncture Service .................................... 90

Table 4.14: Symptoms/Concerns Identified by Participants in MYCaW .................. 91

Table 4.15: Participant Symptoms Concerns Measured at Baseline and at the End

of Acupuncture .......................................................................................... 92
Table 4.16: Qualitative Analysis of Concerns into Super Categories ........................ 93

Table 4.17: Other Concerns Affecting Health Categorised into Super Categories.... 94

Table 4.18: Qualitative Analysis of Important Aspects of the Service ...................... 95

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List of Abbreviations

ADL Activities Of Daily Living
AE Adverse Events
ANZCTR Australian New Zealand Clinical Trials Registry
CAM Complementary And Alternative Medicine
CI Confidence Interval
CINV Chemotherapy-Induced Nausea And Vomiting
CMF Cyclophosphamide, Methotrexate And Fluorouracil
CNS Central Nervous System
EA Electro-Acupuncture
EBP Evidence-Based Practice
EERW Enriched Enrolment With Randomised Withdrawal
FLIE Functional Living Index Emesis
HRQOL Health-Related Quality-Of-Life
INVR Index Of Nausea, Vomiting And Retching
IQR Interquartile Range
JBI Joanna Briggs Institute
MD Mean Difference
MYCaW Measure Yourself Concern And Wellness
MYMOP Measure Yourself Medical Outcome Profile
NIDL No Or Minimal Impact On Daily Life
NRS Number Rating Scale
QoL Quality Of Life
RCT Randomised Controlled Trial
STRICTA Standards For Reporting Interventions In Controlled Trials Of
Acupuncture
TCM Traditional Chinese Medicine
TNM Tumour, Nodes And Metastasis
UK United Kingdom

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