J Daniels,^1,2* J Gray,^3,4 H Pattison,⁵ T Roberts,⁶ E Edwards,⁴ P Milner,⁴ L Spicer,⁷ E King,² RK Hills,² R Gray,² L Buckley,² L Magill,² N Elliman,⁵ B Kaambwa,⁶ S Bryan,⁶ R Howard,⁷ P Thompson³ and KS Khan^1,4

¹University of Birmingham, Academic Department of Obstetrics and Gynaecology, Birmingham Women's Hospital, UK
²University of Birmingham, Clinical Trials Unit, UK
³Birmingham Children's Hospital NHS Foundation Trust, UK
⁴Birmingham Women's Healthcare NHS Foundation Trust, UK
⁵Aston University, School of Life and Health Sciences, UK
⁶University of Birmingham, Department of Health Economics, UK
⁷Barking, Havering and Redbridge Hospitals NHS Trust, UK

*Corresponding author

Background

Early-onset group B streptococcus (EOGBS) disease is the leading cause of serious neonatal sepsis in developed countries. It is transmitted to neonates during birth from colonised mothers, in whom it is an opportunistic pathogen harboured in the vagina or rectum. Intrapartum antibiotic prophylaxis (IAP) given to the mother reduces the risk of EOGBS disease in the newborn by reduction of maternal transmission and protection of the neonate, providing it is administered sufficiently early before delivery. There is disagreement about the best screening strategies, with the UK currently recommending IAP on the basis of risk factors present at the time of labour. In some countries, screening of women for GBS colonisation is undertaken at 35–37 weeks' gestation with culture of vaginal and/or rectal swabs. This report assesses the accuracy and acceptability of an alternative approach, based on intrapartum rapid testing for maternal GBS colonisation, to determine which women should receive IAP, and models its cost-effectiveness against alternative strategies.

Objectives

This health technology assessment completed three distinct pieces of work:

• to determine the accuracy (sensitivity, specificity, predictive values) of polymerase chain reaction (PCR) and optical immunoassay (OIA) technologies as rapid tests for maternal vaginal and rectal GBS colonisation at the onset of labour using selective enrichment culture as the reference standard
• to determine the acceptability of rapid testing for GBS colonisation among pregnant women of different age and ethnic groups
• to determine the cost and cost-effectiveness of rapid intrapartum testing for maternal GBS colonisation to prevent EOGBS disease, and compare this with other strategies for screening and prevention.

Methods

A primary test accuracy study obtained swabs at the onset of labour from 1400 women from two large maternity units to compare the results of vaginal and rectal PCR and OIA (index tests) with the reference standard of enriched culture of combined vaginal and rectal swabs. The study compared the accuracy of index tests, determined the relative accuracies of tests on vaginal and rectal swabs, evaluated whether test accuracy varied according to the presence or absence of maternal risk factors, and explored the determinants of neonatal colonisation.

Acceptability of testing to participants was evaluated through a structured questionnaire administered as soon as possible after delivery. The characteristics of those who declined to take part in the study when first approached were also analysed. Acceptability of rapid testing to staff was evaluated through two focus groups with midwives who had taken part in the study.

For the economic evaluation resource usage data were collected alongside the test accuracy study to establish the cost of rapid testing. A decision-analytic model was constructed to assess the cost-effectiveness of various screening and prevention strategies, using a perspective of the NHS and an outcome of cost per case of EOGBS disease or death avoided.

Results

Main findings of test accuracy study

PCR was significantly more accurate than OIA for the detection of maternal GBS colonisation, for all combinations of index and reference test. Combined vaginal or rectal swab index tests were more sensitive than either test considered individually [combined swab sensitivity for PCR 84% (95% CI 79–88%); vaginal swab 58% (52–64%); rectal swab 71% (66–76%)]. The highest sensitivity for PCR came at the cost of lower specificity [combined specificity 87% (95% CI 85–89%); vaginal swab 92% (90–94%); rectal swab 92% (90–93%)]. The sensitivity and specificity of rapid tests varied according to the presence or absence of maternal risk factors but not consistently. PCR results were determinants of neonatal GBS colonisation, but maternal risk factors were not.

Overall levels of acceptability for rapid testing amongst participants were high and there was no evidence that screening had raised anxiety. They did not find the process of swabbing unpleasant, although vaginal swabs were more acceptable than rectal swabs. Compared with white British women, South Asian women were less likely to have participated in the study and were less happy with the sampling procedure and with the prospect of rapid testing as part of routine care; they were also more likely to prefer professional judgement as the basis for treatment. Midwives were generally positive towards rapid testing if practical problems could be overcome but had concerns that it might lead to overtreatment and unnecessary interference in births.

The rapid tests were both relatively expensive compared with the other strategies (PCR test £29.95; OIA test £16.09). Modelling analysis revealed that the most cost-effective strategy was to provide routine IAP to all women without screening. As this was deemed unlikely to be acceptable to the majority of women and midwives, the analysis was repeated with the removal of this strategy. Here, screening based on a culture test at 35–37 weeks' gestation, with the provision of antibiotics to all women who screened positive, was most cost-effective, assuming that all women in premature labour would receive IAP. The results were sensitive to very small increases in costs and changes in other assumptions. Screening using a rapid test, whether PCR or OIA, and based on rectal or vaginal swabs combined, was not cost-effective, based on its current sensitivity, specificity and cost.

Conclusions

Implications for health care

Although PCR performed better than OIA, neither rapid test evaluated was sufficiently accurate to recommend it for routine use in clinical practice. Rectal swabbing was less acceptable and the technologies need to be further refined for point-of-care use. The most cost-effective approach to reducing EOGBS disease is likely to be the provision of IAP to all women without testing. If this strategy is discarded on grounds of acceptability, IAP directed by screening with enriched culture at 35–37 weeks' gestation, with IAP to all women in premature labour, becomes cost-effective. However, it is premature to suggest the implementation of either strategy at present.

Recommendations for research

The relative effectiveness, feasibility and acceptability to women of screening by enriched culture and provision of routine IAP should be explored. Further refinements of rapid tests would be required to improve accuracy to make point-of-care testing practicable at reduced cost. Any new development would require further evaluation and comparison with existing strategies.

Publication

Daniels J, Gray J, Pattison H, Roberts T, Edwards E, Milner P, et al. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess 2009;13(42).

NIHR Health Technology Assessment programme

The Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.

The research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service'.

The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projects.

First is the commissioned route. Suggestions for research are actively sought from people working in the NHS, from the public and consumer groups and from professional bodies such as royal colleges and NHS trusts. These suggestions are carefully prioritised by panels of independent experts (including NHS service users). The HTA programme then commissions the research by competitive tender.

Second, the HTA programme provides grants for clinical trials for researchers who identify research questions. These are assessed for importance to patients and the NHS, and scientific rigour.

Third, through its Technology Assessment Report (TAR) call-off contract, the HTA programme commissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring together evidence on the value of specific technologies.

Some HTA research projects, including TARs, may take only months, others need several years. They can cost from as little as £40,000 to over £1 million, and may involve synthesising existing evidence, undertaking a trial, or other research collecting new data to answer a research problem.

The final reports from HTA projects are peer reviewed by a number of independent expert referees before publication in the widely read journal series Health Technology Assessment.

Criteria for inclusion in the HTA journal series

Reports are published in the HTA journal series if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.

Reviews in Health Technology Assessment are termed 'systematic' when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.

The research reported in this issue of the journal was commissioned by the HTA programme as project number 02/38/04. The contractual start date was in October 2004. The draft report began editorial review in October 2007 and was accepted for publication in November 2008. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.

Editor-in-Chief: Professor Tom Walley CBE
Series Editors: Dr Aileen Clarke, Dr Chris Hyde, Dr John Powell, Dr Rob Riemsma and Professor Ken Stein