Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and ...

286 Pages·2008·1.04 MB·English

Health Technology Assessment 2008;Vol. 12: No. 6
Methods of prediction and prevention of
pre-eclampsia: systematic reviews of
accuracy and effectiveness literature with
economic modelling
CA Meads, JS Cnossen, S Meher, A Juarez-Garcia,
G ter Riet, L Duley, TE Roberts, BW Mol,
JA van der Post, MM Leeflang, PM Barton,
CJ Hyde, JK Gupta and KS Khan
March 2008
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Methods of prediction and prevention of
pre-eclampsia: systematic reviews of
accuracy and effectiveness literature with
economic modelling
1* 2 3 4
CA Meads, JS Cnossen, S Meher, A Juarez-Garcia,
2,5 6 4 7
G ter Riet, L Duley, TE Roberts, BW Mol,
7 8 4
JA van der Post, MM Leeflang, PM Barton,
1 9 9
CJ Hyde, JK Gupta and KS Khan
1 Department of Public Health and Epidemiology,
University of Birmingham, UK
2 Department of General Practice, Academic Medical Center, Amsterdam,
The Netherlands
3 University of Liverpool, Liverpool Women’s Hospital, UK
4 Department of Health Economics, University of Birmingham, UK
5 Horten Centre, University of Zurich, Switzerland
6 Bradford Institute for Health Research, Bradford Royal Infirmary, UK
7 Department of Obstetrics and Gynaecology, Academic Medical Center,
Amsterdam, The Netherlands
8 Department of Clinical Epidemiology and Biostatistics, Academic Medical
Center, Amsterdam, The Netherlands
9 Birmingham Women’s Hospital, UK
* Corresponding author
Declared competing interests of authors:L Duley was a member of the steering
committee and author on the Barbados 1998 aspirin trial and the Vitamins in Pregnancy (VIP)
trial and was co-investigator in the PARIS review. CJ Hyde is a member of the Editorial board
for Health Technology Assessmentbut was not involved in the editorial process for this report.
Published March 2008
This report should be referenced as follows:
Meads CA, Cnossen JS, Meher S, Juarez-Garcia A, ter Riet G, Duley L, et al. Methods of
prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness
literature with economic modelling. Health Technol Assess2008;12(6).
Health Technology Assessmentis indexed and abstracted in Index Medicus/MEDLINE, Excerpta
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Health Technology Assessment2008; Vol. 12: No. 6
Abstract
Methods of prediction and prevention of pre-eclampsia:
systematic reviews of accuracy and effectiveness literature
with economic modelling
CA Meads,1* JS Cnossen,2 S Meher,3 A Juarez-Garcia,4 G ter Riet,2,5 L Duley,6
TE Roberts,4 BW Mol,7 JA van der Post,7 MM Leeflang,8 PM Barton,4 CJ Hyde,1
JK Gupta9 and KS Khan9
1Department of Public Health and Epidemiology, University of Birmingham, UK
2Department of General Practice, Academic Medical Center, Amsterdam, The Netherlands
3University of Liverpool, Liverpool Women’s Hospital, UK
4Department of Health Economics, University of Birmingham, UK
5Horten Centre, University of Zurich, Switzerland
6Bradford Institute for Health Research, Bradford Royal Infirmary, UK
7Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, The Netherlands
8Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, The Netherlands
9Birmingham Women’s Hospital, UK
* Corresponding author
Objectives: To investigate the accuracy of predictive proteinuria, seemed to offer the promise of high
tests for pre-eclampsia and the effectiveness of sensitivity, without compromising specificity, but these
preventative interventions for pre-eclampsia. Also would require further investigation. For the 16
to assess the cost-effectiveness of strategies effectiveness reviews, the quality of included studies
(test–intervention combinations) to predict and was variable. The largest review was of antiplatelet
prevent pre-eclampsia. agents, primarily low-dose aspirin, and included 51
Data sources: Major electronic databases were trials (36,500 women). This was the only review where
searched to January 2005 at least. the intervention was shown to prevent both pre-
Review methods: Systematic reviews were carried eclampsia and its consequences for the baby. Calcium
out for test accuracy and effectiveness. Quality supplementation also reduced the risk of pre-
assessment was carried out using standard tools. For eclampsia, but with some uncertainty about the impact
test accuracy, meta-analyses used a bivariate approach. on outcomes for the baby. The only other intervention
Effectiveness reviews were conducted under the associated with a reduction in RR of pre-eclampsia was
auspices of the Cochrane Pregnancy and Childbirth rest at home, with or without a nutritional supplement,
Group and used standard Cochrane review methods. for women with normal blood pressure. However, this
The economic evaluation was from an NHS review included just two small trials and its results
perspective and used a decision tree model. should be interpreted with caution. The cost of most of
Results: For the 27 tests reviewed, the quality of the tests was modest, ranging from £5 for blood tests
included studies was generally poor. Some tests such as serum uric acid to approximately £20 for
appeared to have high specificity, but at the expense of Doppler tests. Similarly, the cost of most interventions
compromised sensitivity. Tests that reached specificities was also modest. In contrast, the best estimate of
above 90% were body mass index > 34, additional average cost associated with an average
(cid:2)-foetoprotein and uterine artery Doppler (bilateral case of pre-eclampsia was high at approximately
notching). The only Doppler test with a sensitivity of £9000. The results of the modelling revealed that
over 60% was resistance index and combinations of prior testing with the test accuracy sensitivities and
indices. A few tests not commonly found in routine specificities identified appeared to offer little as a
practice, such as kallikreinuria and SDS-PAGE way of improving cost-effectiveness. Based on the iii
© Queen’s Printer and Controller of HMSO 2008. All rights reserved.
Abstract
evidence reviewed, none of the tests appeared be the provision of an effective, affordable and safe
sufficiently accurate to be clinically useful and the intervention applied to all mothers without prior
results of the model favoured no-test/treat-all testing to assess levels of risk. It is probably premature
strategies. Rest at home without any initial testing to suggest the implementation of a treat-all
appeared to be the most cost-effective ‘test–treatment’ intervention strategy at present, however the feasibility
combination. Calcium supplementation to all women, and acceptability of this to women could be explored.
without any initial testing, appeared to be the second Rigorous evaluation is needed of tests with modest cost
most cost-effective. The economic model provided whose initial assessments suggest that they may have
little support that any form of Doppler test has high levels of both sensitivity and specificity. Similarly,
sufficiently high sensitivity and specificity to be cost- there is a need for high-quality, adequately powered
effective for the early identification of pre-eclampsia. It randomised controlled trials to investigate whether
also suggested that the pattern of cost-effectiveness interventions such as advice to rest are indeed effective
was no different in high-risk mothers than the low-risk in reducing pre-eclampsia. In future, an economic
mothers considered in the base case. model should be developed that considers not just
Conclusions: The tests evaluated are not sufficiently pre-eclampsia, but other related outcomes, particularly
accurate, in our opinion, to suggest their routine use in those relevant to the infant such as perinatal death,
clinical practice. Calcium and antiplatelet agents, preterm birth and small for gestational age. Such a
primarily low-dose aspirin, were the interventions modelling project should make provision for primary
shown to prevent pre-eclampsia. The most cost- data collection on the safety of interventions and their
effective approach to reducing pre-eclampsia is likely to associated costs.
iv
Health Technology Assessment2008; Vol. 12: No. 6
Contents
Glossary and list of abbreviations ............. vii Recommendations for practice .................. 108
Recommendations for research ................. 108
Executive summary .................................... ix
Acknowledgements .................................... 111
1 Objectives and background ....................... 1
Aims ............................................................ 1 References .................................................. 113
Description of underlying health
problem ...................................................... 1 Appendix 1 Protocol for the effectiveness
Objectives of this project ............................ 6 reviews ........................................................ 121
2 Systematic review methods ...................... 9 Appendix 2 Test accuracy search
Protocol development ................................ 9 strategy ....................................................... 123
The research question ................................ 9
Methods for test accuracy reviews .............. 9 Appendix 3 Data extraction form ............. 125
Methods for Cochrane reviews .................. 14
Modifications to the protocol and original Appendix 4 Effectiveness reviews generic
grant proposal ............................................ 16 search strategy ............................................ 133
Methods for economic evaluation .............. 16
Project reporting ........................................ 16 Appendix 5 Cochrane review subgroup
categorisation and list of outcomes ........... 135
3 Test accuracy reviews ................................ 17
Study selection ........................................... 17 Appendix 6 Comparison between proposed
Examinations .............................................. 18 diagnostic and screening tests and
Investigations – blood ................................ 18 treatments for pre-eclampsia to be
Investigations – urine ................................. 31 systematically reviewed and final systematic
Investigations – haemodynamic ................. 35 reviews completed ...................................... 139
Discussion of test accuracy ......................... 46
Appendix 7 Test accuracy tables of
4 Clinical effectiveness reviews .................... 53 methodological and reporting
Study selection ........................................... 53 characteristics of included studies ............. 141
Presentation of results ................................ 53
Antenatal care interventions ...................... 53 Appendix 8 Diagnostic test quality charts 169
Lifestyle interventions ................................ 53
Nutrition and dietary interventions ........... 59 Appendix 9 Effectiveness reviews tables of
Pharmacological interventions ................... 71 methodological and reporting
Discussion of results of clinical characteristics of included studies ............. 177
effectiveness reviews ................................... 78
Appendix 10 Data extraction sheet for
5 Economic evaluation .................................. 85 economics section ....................................... 215
Methods for economic evaluation .............. 85
Results of economic evaluation .................. 94 Appendix 11 Economic evaluation case 6
Discussion of results of economic results ......................................................... 217
evaluation ................................................... 100
Appendix 12 References for reviews ......... 219
6 Conclusions ................................................ 107
Introduction ............................................... 107 Health Technology Assessment reports
Main findings ............................................. 107 published to date ....................................... 251
Strengths of the report ............................... 107
Limitations of the project .......................... 107 Health Technology Assessment
Overall conclusion ...................................... 108 Programme ................................................ 267 v

Health Technology Assessment2008; Vol. 12: No. 6
Glossary and list of abbreviations
Technical terms and abbreviations are used throughout this report. The meaning is usually clear from
the context, but a glossary is provided for the non-specialist reader. In some cases, usage differs in the
literature, but the term has a constant meaning throughout this review.
Glossary
Aneuploidy The condition of having less I2 statistic Indication of heterogeneity of
than or more than the normal diploid number studies in a forest plot.
of chromosomes.
Multiples of median When two analytical
Extra Domain A and B in fibronectin methods agree, or differ by a proportional
molecule Although fibronectin is encoded by amount, conversion to multiples of median can
only one gene, this protein exists in a number be used to simplify the clinical interpretation of
of variant isoforms due to alternate splicing results.
and/or post-translational modifications.
List of abbreviations
ACTH adrenal corticotrophic hormone fDNA foetal DNA
AFP (cid:2)-foetoprotein FN fibronectin
fp, fn false positive, false negative
APEC Action on Pre-Eclampsia
numbers
AUN any unilateral notching
HCG human chorionic gonadotrophin
BMI body mass index
HELLP haemolysis, elevated liver
enzymes and low platelets
BNF British National Formulary
ICER incremental cost-effectiveness
CEAC cost-effectiveness acceptability ratio
curve
IPD individual patient data
CI confidence interval
MoM multiples of median
DHEA-s dehydroepiandrosterone sulfate
NICU neonatal intensive care unit
DIC disseminated intravascular
NNT number-needed-to-treat
coagulation
NPV negative predictive value
E3 unconjugated oestriol
PMS premenstrual syndrome
ED-A, ED-B extra domain A and B in
fibronectin molecule PE pre-eclampsia
continued
vii
© Queen’s Printer and Controller of HMSO 2008. All rights reserved.
Glossary and list of abbreviations
List of abbreviations continued
PPV positive predictive value SPSS Statistical Package for the Social
Sciences
PSA probabilistic sensitivity analysis
sROC summary receiver–operator
RCT randomised controlled trial characteristic
RD risk difference SUA serum uric acid
ROC receiver–operator characteristic tp, tn true positive, true negative
numbers
RR relative risk
UCCR urinary calcium/creatinine ratio
SD standard deviation
UCE urinary calcium excretion
SDS-PAGE sodium dodecyl sulfate
polyacrylamide gel WHO World Health Organization
electrophoresis
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