Title: A clinical and economic evaluation of screening and diagnostic tests to identify and treat women with gestational diabetes: association between maternal risk factors glucose levels and adverse outcomes
Funder: Department of Health (England)

Abstract: Gestational diabetes (GDM) affects a significant proportion of women each year the incidence is increasing globally and is associated with a range of adverse perinatal and longer term health outcomes which may repeat across generations. Various strategies are used to identify women with GDM [1] with no clear evidence of superiority for any one method over another and there also remains uncertainty how GDM is best identified and at what glycaemic threshold treatment should begin.This uncertainty partly reflects lack of clarity around glycaemic thresholds for diagnosis. Recent evidence shows a graded positive linear association between fasting and postload glucose level and adverse outcomes [2]. This research will use systematic reviews analysis of new individual participant data and contemporary modelling techniques to identify the most cost and clinically-effective strategies for identifying GDM and for preventing associated adverse health outcomes. More specifically the objectives will: (1) determine adverse outcome incidence rates associated with incremental increases in maternal glucose level including: large for gestational age operative delivery birth injury maternal postnatal length of hospital stay admission to neonatal unit and perinatal death (2) estimate the incidence of GDM in the contemporary UK obstetric population and in subgroups of the population for example by ethnicity and by BMI category; (3) compare the characteristics of screening tests and (4) compare the characteristics of diagnostic tests in relation to key perinatal and longer term maternal outcomes and (5) determine the most cost and clinically-effective methods to treat GDM to reduce adverse outcomes. The objectives will be accomplished using relevant data from studies identified through systematic searching carried out by a team of information specialists; included studies will be quality assessed and analysed by the research teams at Bradford and York and evidence synthesised as appropriate to produce ranges of estimates of the key parameters. A new analysis of individual participant data from cohort studies will be undertaken using the Born in Bradford (BIB) cohort. Comparisons will include (a) universal non-blood based risk factor screening followed by selective 75g OGTT; (b) universal fasting glucose screening followed by selective 75g OGTT; (c) universal random glucose screening followed by 75g OGTT; (d) universal HbA1c followed by 75g OGTT and (e) universal diagnostic testing with 75g OGTT. We will extend our recent systematic review [3] and compare how outcomes differ for OGTT undertaken at different times in pregnancy and with different doses and types of glucose load. Incidence of GDM and associations between incremental increases in maternal glucose levels and adverse outcomes including macrosomia birth injury and instrumental birth and long-term health outcomes (maternal insulin and glucose dysfunction) will be examined. The costs of treatment for GDM will be estimated from previous economic evaluations and from routine UK data sources (for example the British National Formulary). The health consequences for the population of untreated/treated GDM will be identified from the reviews and new analyses and their associated costs will be estimated from previous economic evaluations and routine UK data sources (e.g. NHS reference costs). Estimates obtained from the literature reviews and the new analyses of individual participant data from BIB and other studies will be used to populate a decision analytic model for the cost and clinical effectiveness analysis [4]. Alternative screening and diagnostic strategies are expected to differ in terms of costs of identifying women with GDM and the proportion of women identified in whom appropriate treatment can be provided. The decision analytic model will allow differences to be translated into differences in total costs and health outcomes from the perspective of the UK NHS [5]. Cost-effectiveness analysis divides the overall participant population into sub-groups of women who would be identified as being at similar baseline risk of adverse events from GDM and similar in terms of response to treatment. Treatments for GDM recommended by guidelines in the UK [6] and their cost-effectiveness will be characterised within the decision analytic model in order to predict for a woman diagnosed with GDM what would be the expected costs and health outcomes in terms of quality adjusted life years. The decision analytic model produced will not only be able to inform policy and practice on screening for GDM it will also identify any key underlying uncertainties which may be worth addressing through further research. The model will be available to the NHS to update in the future as new data emerge and so be a useful resource for NHS decision makers.1. Scott DA Loveman E McIntyre L Waugh N (2002) Screening for gestational diabetes: a systematic review and economic evaluation. HTA 6: 1-161.2. HAPO study cooperative research group (2008) Hyperglycemia and Adverse Pregnancy Outcomes. N Engl J Med 358: 1991-2002.3. Farrar D Lawlor D Duley L. Different testing strategies for diagnosing gestational diabetes mellitus to improve maternal and infant health. Cochrane Database of Syst Rev 2011;Issue 10.Art. No.:CD007122.4. Philips Z Ginnelly L Sculpher M et al. Review of guidelines for good practice in decision-analytic modelling in health technology assessment. HTA 2004; 8(36).5.NICE. Guide to the methods of technology appraisal. London: NICE 2008 http://www.nice.org.uk/media/B52/A7/TAMethodsGuideUpdatedJune2008.pdf6. NICE. (2008) Diabetes in pregnancy: management of diabetes and its complications from pre-conception to the postnatal period. National collaborating center for Womens and Childrens Health.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH;METABOLIC AND ENDOCRINE