The HOPEFUL Study

264 Pages·2008·1.03 MB·English

Health Technology Assessment 2008; Vol. 12: No. 5
A multi-centre retrospective cohort
study comparing the efficacy, safety and
cost-effectiveness of hysterectomy
and uterine artery embolisation for
the treatment of symptomatic uterine
fibroids. The HOPEFUL study
A Hirst, S Dutton, O Wu, A Briggs,
C Edwards, L Waldenmaier, M Maresh,
A Nicholson and K McPherson
March 2008
Health Technology Assessment
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A multi-centre retrospective cohort
study comparing the efficacy, safety and
cost-effectiveness of hysterectomy
and uterine artery embolisation for
the treatment of symptomatic uterine
fibroids. The HOPEFUL study
1 1 2 2
A Hirst, S Dutton, O Wu, A Briggs,
3 1 4
C Edwards, L Waldenmaier, M Maresh,
5 1*
A Nicholson and K McPherson
1
Nuffield Department of Obstetrics and Gynaecology, University of
Oxford, UK
2
Section of Public Health and Health Policy, University of Glasgow, UK
3
Student Support and Learning Centre, University of Leicester and
Qualitative Focus, UK
4
Department of Obstetrics and Gynaecology, St Mary’s Hospital for
Women and Children, Manchester, UK
5
Department of Radiology, Leeds General Infirmary, Leeds, UK
* Corresponding author
Declared competing interests of authors: none
Published March 2008
This report should be referenced as follows:
Hirst A, Dutton S, Wu O, Briggs A, Edwards C, Waldenmaier L, et al. A multi-centre
retrospective cohort study comparing the efficacy, safety and cost-effectiveness of
hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine
fibroids. The HOPEFUL study. Health Technol Assess 2008;12(5).
Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE,
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Health Technology Assessment 2008; Vol. 12: No. 5
Abstract
A multi-centre retrospective cohort study comparing the efficacy,
safety and cost-effectiveness of hysterectomy and uterine artery
embolisation for the treatment of symptomatic uterine fibroids.
The HOPEFUL study
1 1 2 2 3 1 4
A Hirst, S Dutton, O Wu, A Briggs, C Edwards, L Waldenmaier, M Maresh,
5 1*
A Nicholson and K McPherson
1 Nuffield Department of Obstetrics and Gynaecology, University of Oxford, UK
2 Section of Public Health and Health Policy, University of Glasgow, UK
3 Student Support and Learning Centre, University of Leicester and Qualitative Focus, UK
4 Department of Obstetrics and Gynaecology, St Mary’s Hospital for Women and Children, Manchester, UK
5 Department of Radiology, Leeds General Infirmary, Leeds, UK
*Corresponding author
Objectives: To examine and compare the medium- measures obtained in the UAE group included
term results of hysterectomy and uterine artery fibroid/uterine size shrinkage and further treatments
embolisation (UAE) as a treatment for symptomatic required for unresolved fibroid symptoms. Data were
uterine fibroids with regard to safety, efficacy, special also gathered on pregnancies post-UAE.
issues in the UAE group, cost-effectiveness, and Results: Data were available for 1108 women
women’s own perspectives on the treatments. (649 UAE and 459 hysterectomy). Fewer complications
Design: Data were collected locally from patients’ were experienced by women in the UAE cohort
hospital records and also from patients themselves by compared to the hysterectomy cohort: hysterectomy
postal questionnaire. Questionnaire data included n = 120 (26.1%), UAE n = 114 (17.6%), adjusted
free-text comments and this qualitative material was odds ratio 0.48 [95% confidence interval (CI) 0.26 to
analysed using constant comparison. A two-stage 0.89]. When only the severe/major complications were
probabilistic decision model was designed to estimate considered, this odds ratio was reduced to 0.25 (95%
UK NHS costs and health outcomes in terms of CI 0.13 to 0.48). Expected general side-effects of UAE
quality-adjusted life-years (QALYs). occurred in 32.7% of the UAE cohort, of which 8.9%
Setting: Eighteen NHS hospital trusts, 17 in England also experienced complications. Obesity and medical
and one in Scotland. co-morbidity predisposed women to complications,
Participants: Eligible women (972 UAE, 762 whereas prophylactic antibiotics appeared to protect
hysterectomies) who had received treatment against both complications and the expected side-
specifically for symptomatic fibroids were identified. effects of UAE. More women in the hysterectomy
Interventions: The UAE patients were treated by cohort reported relief from fibroid symptoms (89%
experienced interventional radiologists and all received versus 80% UAE, p < 0.0001) and feeling better (81%
their index UAE prior to the end of 2002, ensuring a versus 74% UAE, p < 0.0001), but only 70%
minimum 2-year follow-up. The average length of (compared with 86% UAE, p = 0.007) would
follow-up was 8.6 years for the hysterectomy cohort recommend their treatment to a friend. In the UAE
and 4.6 years for the UAE cohort. cohort, 18.3% of the women went on to receive one
Main outcome measures: Primary outcome or more further fibroid treatments including
measures were complication rates to assess the hysterectomy (11.2%). After adjusting for differential
comparative safety of the two interventions. Secondary time of folow-up, the UAE women had up to a 23%
outcome measures related to treatment efficacy (95% CI 19 to 27%) likelihood of requiring further
including resolution of symptoms and patient-reported treatment. The free-text data indicated that many
satisfaction with treatment. Further efficacy outcome women, in both cohorts, felt that their treatment had iii
© Queen’s Printer and Controller of HMSO 2008. All rights reserved.
Abstract
been a complete success. In the UAE cohort there were taking account of complications, expected side-effects
several areas where expectations were apparently high associated with the procedure and subsequent
and outcome had not fulfilled their expectations. re-treatments for women with a preference for
Disappointment was expressed mainly about uterus preservation. It is important to improve the
continuation or return of symptoms or failure to become management of expectations following UAE,
pregnant. Many continued to have remaining questions particularly regarding fertility. The data suggested that
about their treatment. The economic analysis indicated fertility and miscarriage rate are consistent with those
that UAE is less expensive than hysterectomy even after of age-matched women with fibroids. UAE is an
further treatments for unresolved or recurrent effective treatment for some women with fibroids and
symptoms are taken into account, with little difference in our trial supports the National Institute for Health and
QALYs between the two treatments. Younger women Clinical Excellence guidance that it should be made
are exposed to the risk of recurrent fibroids and available as one of the options for treatment, with a
subsequent additional procedures over a longer period possible reduction in the need for hysterectomy as the
and consequently UAE may no longer be cost-effective. first-line treatment. Further research is needed into
Conclusions: The study results suggest that both UAE which women will be treated most successfully by
and hysterectomy are safe. No unexpected problems UAE, the best method of achieving effective
were detected following UAE after a long follow-up embolisation, advice for women who desire future
period (average 5 years). Complications are less fertility, the role of prophylactic antibiotics in UAE, and
common for UAE than hysterectomy. The cost- the effects of HRT use after UAE on recurrence of
effectiveness analysis favours embolisation even after fibroid symptoms.
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Health Technology Assessment 2008; Vol. 12: No. 5
Contents
List of abbreviations .................................. vii Predictors of outcome ................................ 77
Post-UAE fertility ........................................ 79
Executive summary .................................... ix Key findings – UAE cohort only ................ 80
1 Background and rationale ......................... 1 8 Health economics ...................................... 81
Uterine fibroids .......................................... 1 Introduction ............................................... 81
Treatments for symptomatic fibroids ......... 1 Literature review ........................................ 81
Status of UAE – evidence review ................ 3 Methods ...................................................... 82
Results ........................................................ 90
2 Methods ..................................................... 17 Discussion ................................................... 92
Study design and objectives: introductory Conclusions ................................................ 95
remarks ....................................................... 17
Participant recruitment .............................. 18 9 Analysis of additional free-text
Treatments .................................................. 19 comments ................................................... 97
Study procedures ........................................ 20 Introduction ............................................... 97
Flow of patient numbers ............................ 29 Free-text comments about the experience
Confounding variables ............................... 29 of hysterectomy .......................................... 97
Outcome measures ..................................... 32
Discussion of hysterectomy findings .......... 102
UAE-specific topics ..................................... 39
Free-text comments about the experience
of UAE ........................................................ 103
3 Analysis ....................................................... 41
Discussion of UAE findings ........................ 108
Statistical analysis ....................................... 41
Conclusions ................................................ 109
Free-text analysis ........................................ 44
Key findings – free-text .............................. 110
Health economics methods ........................ 45
10 Discussion ................................................... 111
4 Results: recruitment, baseline
Introduction ............................................... 111
characteristics, confounders and
Methodological/design issues ..................... 111
missing values ............................................. 47
Results ........................................................ 112
Recruitment ................................................ 47
Baseline characteristics .............................. 47
11 Conclusions ................................................ 117
Confounders ............................................... 50
Missing values and primary outcome Introduction ............................................... 117
analysis ....................................................... 52 Implications for healthcare ........................ 117
Key findings – baseline characteristics ....... 52 Implications for further research ............... 119
HOPEFUL study conclusions .................... 120
5 Results: primary outcome measures ......... 53
Comparative safety (UAE versus Hyst) ...... 53 Acknowledgements .................................... 121
UAE-only: general side-effects ................... 57
Key findings – primary outcomes (safety) .. 58 References .................................................. 123
6 Results: secondary outcome measures ..... 61 Appendix 1 UAE collaborators: for each
Comparative efficacy (UAE versus Hyst) ... 61 centre the lead clinician (principal
UAE-only efficacy ....................................... 70 investigator) and researcher/research
Key findings – secondary outcomes nurse are acknowledged ............................. 127
(efficacy) ..................................................... 75
Appendix 2 Hysterectomy collaborators:
7 Results: UAE-specific topics ....................... 77 for each centre the lead clinician (principal
Factors influencing choice of treatment investigator) and researcher/research nurse
(Q21) .......................................................... 77 are acknowledged ....................................... 129
v
Contents
Appendix 3 Trial steering committee Appendix 12 Patient questionnaire ........... 189
members ..................................................... 131
Appendix 13 Patient questionnaire
Appendix 4 Initial patient contact letter .. 133 4-week reminder letter ............................... 201
Appendix 5 Patient information sheet ...... 135 Appendix 14 Primary outcome analyses –
details of logistic regression and
Appendix 6 HOPEFUL consent form ...... 139 coefficients .................................................. 203
Appendix 7 Cause of death recorded on Appendix 15 Health economics ................ 207
death certificates ........................................ 141
Appendix 16 Q24a and f – expectations not
Appendix 8 Second letter to non-consenters fulfilled and why and problems caused by
(first chase) ................................................. 143 the treatment .............................................. 211
Appendix 9 Non-consenters reasons tick Health Technology Assessment reports
box sheet .................................................... 145 published to date ....................................... 229
Appendix 10 UAE clinical data form and Health Technology Assessment
instruction sheet ......................................... 147 Programme ................................................ 245
Appendix 11 Hysterectomy clinical data
form and instruction sheet ......................... 173
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Health Technology Assessment 2008; Vol. 12: No. 5
List of abbreviations
ACOG American College of Obstetricians MREC Multi-Centre Research Ethics
and Gynecologists Committee
BMI body mass index MRI magnetic resonance imaging
BP blood pressure NICE National Institute for Health and
Clinical Excellence
BSIR British Society of Interventional
Radiology NRS numerical rating scale
NSAID non-steroidal anti-inflammatory
CAS carotid artery stenting
drug
CI confidence interval
NSTS NHS Strategic Tracing Service
D&C dilatation and curettage
OR odds ratio
DCRI Duke Clinical Research Institute PES post-embolisation syndrome
DUB dysfunctional uterine bleeding PI principal investigator
DVT deep vein thrombosis POF premature ovarian failure
FEMISA Fibroid Embolisation: Information, PVA poly(vinyl alcohol)
Support and Advice
QALY quality-adjusted life-year
GnRH gonadotrophin-releasing hormone
QoL quality of life
GSE general side-effect (of UAE)
RCOG Royal College of Obstetricians and
HMB heavy menstrual bleeding Gynaecologists
HOPEFUL Hysterectomy Or Percutaneous RCR Royal College of Radiologists
Embolisation For Uterine
RCT randomised controlled trial
Leiomyomata
RR relative risk
HRQoL health-related quality of life
SAE serious adverse event
HRT hormone replacement therapy
SD standard deviation
Hyst hysterectomy cohort
SF-36 Short Form with 36 Items
IBS irritable bowel syndrome
SIR Society of Interventional Radiology
ITT intention-to-treat
TCRE transcervical resection of the
LREC Local Research Ethics Committee endometrium
continued
vii
© Queen’s Printer and Controller of HMSO 2008. All rights reserved.
List of abbreviations
List of abbreviations continued
UAE uterine artery embolisation US ultrasound
UFS-QOL Uterine Fibroid Symptom and VALUE Vaginal, Abdominal or
Quality of Life Questionnaire Laparoscopic Uterine Excision
All abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or
it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices in which case
the abbreviation is defined in the figure legend or at the end of the table.
viii