Title: QUIDS – Quantitative Fibronectin to help Decision-making in women with Symptoms of Preterm Labour
Funder: Chief Scientist Office, Scotland

Abstract: RESEARCH QUESTION: In women with symptoms suggestive of preterm labour what is the prognostic value of quantitative fetal fibronectin (qfFN) for ruling out preterm labour at different thresholds? AIM: To develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using qfFN. DESIGN: Focus group consultation with women, their partners and caregivers, to assess decisional needs. IPD meta-analysis of existing data sets to develop a prognostic model using qfFN and other risk factors based and evaluate the added value of quantitative fFN towards model performance. Prospective cohort study in eight UK sites to validate (+/- refine) prognostic model. SETTING: IPD meta-analysis:- 4 European studies of women with symptoms of preterm labour. Prospective cohort study:- 8 UK consultant-led maternity units. TARGET POPULATION: Women with signs and symptoms of preterm labour at 24-34 weeks gestation in whom admission, transfer or treatment is being considered. HEALTH TECHNOLOGIES BEING ASSESSED: qfFN MEASUREMENT OF COSTS AND OUTCOMES: Primary outcome will be ability of the prognostic model to rule out preterm birth within 7 days. Other endpoints of the model will be influenced by focus groups. IPD meta-analysis will develop a prognostic model including qfFN concentration as a risk factor, in addition to other important risk factors, and evaluate added value of qfFN in prognostic model performance. The prognostic model will be validated in the prospective cohort and refined as necessary. An economic analysis will be undertaken from an NHS perspective to assess potential cost-effectiveness of theqfFN prognostic model. A decision analytic model will be built and populated with existing data on current practice and resource use and diagnostic outcome data from the prospective cohort study, reporting outcomes in terms of the incremental cost per QALY gained. SAMPLE SIZE: IPD meta-analysis:- 4 studies, 1,835 women and 171 events of preterm delivery within 7 days of testing. Prospective Cohort Study:- 1600 women with estimated 96-192 events of preterm delivery within 7 days of testing RECRUITMENT AND DATA COLLECTION: A member of clinical staff will identify potentially eligible participants, provide a patient information leaflet and invite consent. Research midwives will collect outcome data from the maternal and neonatal clinical records. TIMETABLE: Aug 2015-Jan 2018. Focus group consultation will be performed in first 3 months. The first iteration of the prognostic model will be prepared by Feb 2016. The prospective cohort study will commence May 2016 and run for 12 months. Our estimated recruitment rate of 4.45% of all maternities is based on a UK study and a prospective feasibility study. Full delivery details of participants will be available 20 weeks after recruitment ends to enable final validation of the prognostic model. A decision support tool will be developed and tested along side the prospective cohort study. TRANSLATION: If the qfFN based decision support tool is able to rule out preterm labour then it will be rapidly translatable into NHS practice. EXPERTISE IN TEAM: Members have the required expertise in preterm labour research, including experience with studies of predictors of preterm labour and fFN, diagnostic tests, multicentre trials, IPD meta-analysis, health economic modeling, patient acceptability, and representation from public

Lay abstract: The clinical diagnosis of preterm labour that leads to delivery is notoriously challenging. Up to 80% of women who have signs and symptoms of preterm labour remain pregnant after 7 days. This means that many women unnecessarily receive therapies aimed at preventing complications in preterm babies, to ensure benefit for the few babies that are actually born preterm. Possible treatments include steroids given to the mother to help mature preterm babies’ lungs; magnesium sulphate to help prevent brain damage in children born preterm; and transfer to a hospital so delivery will occur at a hospital with appropriate neonatal care facilities. In addition, treatments called tocolytics can be given to try to delay delivery until steroids are effective (48 hours) and to allow transfer to a different hospital, but there is little evidence that they improve outcomes for babies. If however, preterm delivery doesn’t occur, these treatments are costly and potentially harmful to babies and women. Hospital admission and transfer can be particularly difficult for families, both financially and emotionally. A test called quantitative fetal Fibronectin (fFN) may help improve diagnosis of preterm labour. The test involves them measurement of fFN in a swab taken at speculum examination (like a smear test), which is part of the assessment of a woman presenting with signs and symptoms of preterm labour. The amount of fFN present in the sample can be measured in an analyzer that provides results in less than 10 minutes. The lower the concentration of fFN in the sample, the less likely preterm delivery is to occur. Although another type of fFN test, which provided a positive or negative result, has been available for some time, the ability to measure the absolute amount of fibronectin is new. This new test has the potential to more accurately rule out preterm labour. The main aim of this research is to see if qfFN can accurately rule out preterm delivery within 7 days of testing. We will analyse previous research data to see if qfFN is likely to be a useful test - either on its own, or in combination with clinical features that may increase the likelihood of preterm delivery (such as history of previous preterm labour or twin pregnancy). We will then determine which combination of features can help diagnose preterm labour most effectively, whilst still being good value to the NHS. In order to ensure that this 'model' works in UK populations, we will try using it to predict preterm delivery in women attending 8 UK maternity units with symptoms of preterm labour, and then adapt it as necessary. We use our findings to develop decision support tool, to help women and clinicians assess how likely preterm delivery is, and decide whether to start treatment or not. We will ask women, their partners and their caregivers which outcomes are most important when making decisions, and how best to present the decision support, to make sure it is relevant to them. We will make the decision support freely available, most likely as a web-based application. The work will be carried out over 30 months, by a team with the necessary expertise to complete the research. Public representatives will be involved in trial design, management and interpretation and dissemination of results. Patient advisory groups will also be regularly consulted, and women and their partners will be involved in the needs assessment to design the decision support.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH