Evidence review A - Diagnostic test accuracy

150 Pages·2017·3.11 MB·English

by  Anne Carty

National Institute for Health and Care
Excellence

Draft
Heavy menstrual bleeding
(update)
Evidence reviews for diagnostic test accuracy in
investigation for women presenting with heavy
menstrual bleeding
NICE guideline TBC
Evidence reviews
August 2017
Draft for Consultation

These evidence reviews were developed
by National Guideline Alliance, hosted by
the Royal College of

DDRRAAFFTT FFOORR CCOONNSSUULLTTAATTIIOONN
Error! No text of specified style in document.

Disclaimer
The recommendations in this guideline represent the view of NICE, arrived at after careful
consideration of the evidence available. When exercising their judgement, professionals are
expected to take this guideline fully into account, alongside the individual needs, preferences
and values of their patients or service users. The recommendations in this guideline are not
mandatory and the guideline does not override the responsibility of healthcare professionals
to make decisions appropriate to the circumstances of the individual patient, in consultation
with the patient and/or their carer or guardian.
Local commissioners and/or providers have a responsibility to enable the guideline to be
applied when individual health professionals and their patients or service users wish to use it.
They should do so in the context of local and national priorities for funding and developing
services, and in light of their duties to have due regard to the need to eliminate unlawful
discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing
in this guideline should be interpreted in a way that would be inconsistent with compliance
with those duties.
NICE guidelines cover health and care in England. Decisions on how they apply in other UK
countries are made by ministers in the Welsh Government, Scottish Government, and
Northern Ireland Executive. All NICE guidance is subject to regular review and may be
updated or withdrawn.

Copyright
© National Institute for Health and Care Excellence, 2017. All rights reserved. NICE copyright
material can be downloaded for private research and study, and may be reproduced for
educational and not-for-profit purposes. No reproduction by or for commercial organisations,
or for commercial purposes, is allowed without the written permission of NICE.
ISBN:
DRAFT FOR CONSULTATION
Error! No text of specified style in document.

Contents
Abbreviations ....................................................................................................................... 7
Diagnosis of heavy menstrual bleeding ............................................................................. 9
Review questions ............................................................................................................ 9
Introduction ..................................................................................................................... 9
Review question 1. What is the diagnostic accuracy of ultrasound and hysteroscopy for
investigation of women presenting with heavy menstrual bleeding? ...................... 9
Introduction ............................................................................................................ 9
Summary of the protocol ........................................................................................ 9
Clinical evidence .................................................................................................. 10
Summary of clinical studies included in the evidence review ............................... 12
Quality assessment of clinical studies included in the evidence review ................ 18
Economic evidence .............................................................................................. 19
Summary of studies included in the economic evidence review ........................... 20
Economic model .................................................................................................. 22
Resource impact .................................................................................................. 25
Evidence statements ........................................................................................... 26
Health economic evidence statements ................................................................. 30
Review question 2. What is the most clinically effective imaging strategy for diagnosing
adenomyosis in women with heavy menstrual bleeding? ..................................... 31
Introduction .......................................................................................................... 31
Summary of the protocol ...................................................................................... 31
Clinical evidence .................................................................................................. 32
Summary of clinical studies included in the evidence review ............................... 33
Quality assessment of clinical studies included in the evidence review ................ 36
Economic evidence .............................................................................................. 36
Summary of studies included in the economic evidence review ........................... 36
Economic model .................................................................................................. 36
Resource impact .................................................................................................. 36
Recommendations............................................................................................................. 39
Investigations for women with HMB ..................................................................... 39
Hysteroscopy for women with suspected polyps, submucosal fibroids or endometrial
pathology ................................................................................................. 39
Endometrial biopsy at the time of hysteroscopy ................................................... 39
Ultrasound ........................................................................................................... 39
Rationale and impact ......................................................................................................... 41
Why the committee made the recommendations .......................................................... 41
Impact of the recommendations on practice .................................................................. 42
The committee’s discussion of the evidence .................................................................. 43
Interpreting the evidence .............................................................................................. 43
4
DRAFT FOR CONSULTATION
Error! No text of specified style in document.

The outcomes that matter most ........................................................................... 43
The quality of the evidence .................................................................................. 43
Benefits and harms .............................................................................................. 44
Cost-effectiveness and resource use ............................................................................ 47
Other factors the committee took into account .............................................................. 48
References ......................................................................................................................... 50
Appendices ........................................................................................................................ 54
Appendix A – Review protocols .................................................................................... 54
Protocol for review question 1. Diagnostic accuracy of ultrasound and hysteroscopy for
investigation of women presenting with heavy menstrual bleeding ........... 54
Protocol for review question 2. Clinically effective imaging strategy for detecting
adenomyosis in women presenting with heavy menstrual bleeding .......... 57
Appendix B – Health economic quality assessment ...................................................... 60
Appendix C – Research recommendations ................................................................... 62
Appendix D – Clinical evidence study selection ............................................................ 66
Appendix E – Literature search strategies ..................................................................... 67
Appendix F – Clinical evidence tables ........................................................................... 73
Appendix G – GRADE tables ........................................................................................ 74
Review question 1. Adapted GRADE tables for diagnostic accuracy of ultrasound and
hysteroscopy for investigations of women presenting with heavy menstrual
bleeding review ........................................................................................ 74
Review question 2. Adapted GRADE tables for the most clinically effective imaging
strategy for diagnosing adenomyosis in women presenting with heavy menstrual
bleeding review ........................................................................................ 93
Appendix H – Forest plots and hierarchical summary receiver operating characteristic
(HSROC) plots ..................................................................................................... 98
Review question 1. Forest plots and HSROC plots for diagnostic accuracy of ultrasound
and hysteroscopy for investigations of women presenting with heavy menstrual
bleeding review ........................................................................................ 98
Review question 2. Forest plots and HSROC plots for the most clinically effective
imaging strategy for diagnosing adenomyosis in women presenting with heavy
menstrual bleeding review ...................................................................... 112
Appendix I – Excluded studies .................................................................................... 116
Clinical studies ................................................................................................... 116
Economic studies ............................................................................................... 148
Appendix J – Diagnostic care pathway ....................................................................... 149

5
DRAFT FOR CONSULTATION

1
2
3
4
5
6
7
8
9
10
11
12
6
Heavy Menstrual Bleeding (update): evidence reviews for diagnostic test accuracy DRAFT
August 2017
DRAFT FOR CONSULTATION
Abbreviations

Abbreviations
1
Abbreviation Definition
2D Two-dimensional
2D-TAUS Two-dimensional transabdominal ultrasound scan
2D-TVUS Two-dimensional transvaginal ultrasound scan
3D Three-dimensional
3D-TAUS Three-dimensional transabdominal ultrasound scan
3D-TVUS Three-dimensional transvaginal ultrasound scan
AUC Area under the curve
BSGE British Society for Gynaecological Endoscopy
CI Confidence interval
D&C Dilatation and curettage
EBx Endometrial biopsy
EQ-5D EuroQol five dimensions questionnaire
FN False negative
FP False positive
GRADE Grading of Recommendations Assessment, Development and Evaluation
HMB Heavy menstrual bleeding
HRQoL Health-related quality of life
HSROC Hierarchical summary receiver operating characteristic
LNG-IUS Levonorgestrel-releasing intrauterine system
LR+ Positive likelihood ratio
LR- Negative likelihood ratio
MRI Magnetic resonance imaging
N/A Not applicable
NGA National Guideline Alliance
NHS National Health Service
NICE National Institute of Health and Care Excellence
NMA Network meta-analysis
NMB Net monetary benefit
OPH Outpatient hysteroscopy
PSA Probabilistic sensitivity analysis
QALY Quality-adjusted life year
QUADAS-2 A quality assessment tool for diagnostic accuracy studies
RCOG Royal College of Obstetricians and Gynaecology
RCT Randomised controlled trial
RPOC Retained products of conception
Sens Sensitivity
SIS Saline infusion sonography
Spec Specificity
TAUS Transabdominal ultrasound scan
TN True negative
TP True positive
TVUS Transvaginal ultrasound scan
2
7
Heavy Menstrual Bleeding (update): evidence reviews for diagnostic test accuracy DRAFT
August 2017
DRAFT FOR CONSULTATION
Abbreviations

1
2
8
Heavy Menstrual Bleeding (update): evidence reviews for diagnostic test accuracy DRAFT
August 2017
DRAFT FOR CONSULTATION
Diagnosis of heavy menstrual bleeding

Diagnosis of heavy menstrual bleeding
1
Review questions
2
3 Review question 1. What is the diagnostic accuracy of ultrasound and hysteroscopy for
4 investigation of women presenting with heavy menstrual bleeding?
5 Review question 2. What is the most clinically effective imaging strategy for diagnosing
6 adenomyosis in women with heavy menstrual bleeding?
Introduction
7
8 Many women presenting to primary care with heavy menstrual bleeding (HMB) will only ever
9 require simple treatment without the need for further investigations. However, some women
10 with HMB may have an underlying pathology, which is often not apparent from the woman’s
11 history or examination and further investigations to identify the cause may be needed. The
12 aim of investigation is to identify structural abnormalities such as submucosal fibroids,
13 endometrial polyps, larger fibroids, or adenomyosis, and to also detect rare and potentially
14 serious pathologies such as endometrial hyperplasia or carcinoma.
15 The identification of structural, focal or histological abnormalities enables targeted treatment,
16 which should result in more effective management. Whilst the cause of HMB will not always
17 be apparent from the investigation, women may also gain reassurance in knowing that no
18 serious pathology is causing their symptoms, and that no focal treatable lesion was missed
19 that make simple treatments less effective.
Review question 1. What is the diagnostic accuracy of
20
ultrasound and hysteroscopy for investigation of women
21
presenting with heavy menstrual bleeding?
22
23 Introduction
24 Ultrasound scan has been the technique most commonly used to investigate causes of
25 heavy menstrual bleeding. Over time, diagnostic hysteroscopy techniques have improved,
26 which has also enabled the development of ‘see-and-treat’ services. Furthermore, new
27 evidence is available on the clinical and cost-effectiveness of different diagnostic techniques
28 in the investigation of women presenting with heavy menstrual bleeding.
29 The aim of this review was to determine the diagnostic accuracy of hysteroscopy and
30 ultrasound in investigation of women presenting with heavy menstrual bleeding, also taking
31 into account patient acceptability and satisfaction as well as the cost-effectiveness of these
32 approaches.
33 Summary of the protocol
34 Please see Table 1 for a summary of the characteristics of this review including population,
35 index tests, reference standard, outcomes and target conditions.
36 Table 1: Summary of the protocol
Population Premenopausal women with heavy menstrual bleeding (HMB).

At least 66% of the population should be women with heavy
menstrual bleeding.
9
Heavy Menstrual Bleeding (update): evidence reviews for diagnostic test accuracy DRAFT
August 2017
DRAFT FOR CONSULTATION
Diagnosis of heavy menstrual bleeding

Index test(s)  Transvaginal ultrasound scan (TVUS)
o Two-dimensional (2D)
o Three-dimensional (3D)
 Transabdominal ultrasound scan (TAUS)
o 2D
o 3D
 Hysteroscopy
o Inpatient/day case (under general anaesthesia/sedation or
spinal/epidural anaesthesia)
o Outpatient vaginoscopy1
o Outpatient all other cases
 Transvaginal ultrasound followed by hysteroscopy if needed
Reference standard  Histopathology
 Ultrasound scan (when compared with hysteroscopy)
 Inpatient hysteroscopy (when compared with outpatient
hysteroscopy)
Outcomes  Sensitivity (sens)
 Specificity (spec)
 Positive likelihood ratio (LR+)
 Negative likelihood ratio (LR-)
 Area under the curve (AUC) if meta-analysis can be conducted
 Patient satisfaction and acceptability
Target condition Examples: Sub-mucous fibroids, polyps, hyperplasia, cancer,
abnormal uterine thickness, synechiae, endometritis, retained
products of conception (RPOC), fibroids less than 3 cm in
diameter, fibroids larger than 3 cm in diameter, congenital
abnormalities.
1 2D: two-dimensional; 3D: three-dimensional; AUC: area under the curve; HMB: heavy menstrual bleeding; LR+:
2 positive likelihood ratio; LR-: negative likelihood ratio; RPOC: retained products of conception; sens: sensitivity;
3 spec: specificity; TAUS: transabdominal ultrasound scan; TVUS: transvaginal ultrasound scan
4 1 Vaginoscopy approach to hysteroscopy is a technique where the hysteroscope is inserted into the vagina and
5 through the cervical canal and into the uterine cavity without a vaginal speculum or cervical instrumentation.
6 For full details see review protocol in Appendix A – Review protocols.
7 Clinical evidence
8 Histopathology was considered as the reference standard to which the diagnostic accuracy
9 of ultrasound and hysteroscopy were compared. Histopathology was derived from surgery
10 specimen from hysterectomy, hysteroscopy-guided biopsy, or dilatation and curettage (D&C).
11 No evidence was found comparing the diagnostic accuracy of hysteroscopy to ultrasound as
12 a reference standards, however, studies that compared the diagnostic accuracy of
13 ultrasound to hysteroscopy as the reference standard were considered instead.
14 The target conditions in which the diagnostic accuracy of these tests were studied included
15 endometrial polyps, fibroids, endometrial hyperplasia, endometrial carcinoma, and any
16 abnormal finding.
17 A combined literature search was undertaken for this review question together with the
18 review question on the diagnostic accuracy of imaging techniques in detecting adenomyosis
19 in women presenting with heavy menstrual bleeding.
20 In addition, relevant studies included in NICE guideline on Heavy menstrual bleeding:
21 assessment and management (CG44) published in 2007 were assessed and included if they
22 fitted the inclusion criteria in the current protocol.
10
Heavy Menstrual Bleeding (update): evidence reviews for diagnostic test accuracy DRAFT
August 2017