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  • Periodic Report Summary 3 - IMPROVED (IMPROvED: IMproved Pregnancy Outcomes by Early Detection; personalized medicine for pregnant women: novel metabolomic and proteomic biomarkers to detect pre-eclampsia and improve outcome.)
FP7

IMPROvED Report Summary

Project ID: 305169
Funded under: FP7-HEALTH
Country: Ireland

Periodic Report Summary 3 - IMPROVED (IMPROvED: IMproved Pregnancy Outcomes by Early Detection; personalized medicine for pregnant women: novel metabolomic and proteomic biomarkers to detect pre-eclampsia and improve outcome.)

Project Context and Objectives:
Pre-eclampsia is a complex pathogenesis that requires a personalised medicine approach. The main goal of this project is therefore to develop a clinically robust predictive blood test for pre-eclampsia, using innovative technologies and utilising novel metabolite and protein biomarkers.

The IMPROvED (IMproved PRegnancy Outcomes by Early Detection) project is a multicentre clinical study aiming to assess and refine two innovative prototype screening tests for pre-eclampsia, a common complication of late pregnancy. Approximately 50 million babies are born to first time mothers worldwide every year and almost 1 in 20 of these pregnancies are complicated by pre-eclampsia. The condition is associated globally with 70,000-80,000 maternal and over 500,000 infant deaths annually. For the mother it can lead to acute problems in the liver, kidneys, brain and the clotting system, and pre-eclampsia is the most important cause of maternal death in Europe - accounting for 17-24% of all maternal deaths.

Identification of women at risk of pre-eclampsia is the first step to effective intervention and prevention. Current screening is based on the presence of clinical features however the majority of women who develop pre-eclampsia are first-time mothers, who commonly have no identifiable clinical risk factors in early pregnancy.

Prompted by the current absence of a clinically useful screening test for pre-eclampsia the IMPROvED consortium aims to develop a robust predictive blood test suitable for use in a clinical environment, employing innovative technologies and utilising novel metabolite and protein biomarkers. Project partners Metabolomics Diagnostics (Ireland) and MyCartis (formerly Pronota, Belgium) have developed two prototype screening tests (ProTest & MetTest) for pre-eclampsia which will be further refined and validated in IMPROvED with the aim of ultimately progressing to regulatory approval and clinical use.

5000 first time mothers will participate in the study by attending at least two and up to four visits with an IMPROvED midwife, in four European countries, Ireland, U.K., the Netherlands and Sweden. At each visit comprehensive clinical data, blood, urine and hair samples are collected. A customised IMPROvED Clinical Data and Biobank Management Database, specifically designed for data management in clinical trials and cohort studies, has been developed by project partner MedSciNet. In parallel to participant recruitment and validation of the ProTest and MetTest, project partner University of Groningen, the Netherlands will assess the health economic benefits of screening tests.

Project Results:
The 3rd reporting period focused on the clinical study and recruitment. Critical to the aims of the clinical study and the IMPROvED project is ensuring quality data and samples are obtained from recruitment sites.

Five recruitment centres were recruiting for this reporting period, across four countries. The framework developed earlier in this project has ensured that quality of samples and data is being achieved at these recruitment sites. The SOPs, training materials, monitoring, and regulations in place continued to be essential quality control tools. A uniformity of process was also achieved through these tools with each site completing the same practices.
Recruitment tools such as poster and flyer that were developed earlier were further utilised to maximum potential in this reporting period. The website http://www.fp7-improved.eu/ and social media (facebook) were used to bolster traditional recruitment methods.

Presently at the close of this reporting period recruitment is ongoing at the coordinating centre in UCC.

Recruitment has now been completed at four centres, Cork continues to recruit. Current figures show that 3,300 participants have been recruited (ie have attended both compulsory visits). Response to the study is positive with almost 80% of women asked to participate, agreeing. Recruitment rates remain positive in Cork an average of 40 new women join every month. Women participating in the study have expressed gratitude in the extra attention and a great sense of pride in being able to help make pregnancies safer for future moms to be.

Over 3223 babies have been born to IMPROvED mothers and end of pregnancy outcome data is currently being collected and entered to the database. When a significant number of participants have had all data collected, monitored and signed off by the principal investigator samples will then be transferred to the Metabolomics Diagnostics and MyCartis. There is currently 1486 participant IDs with data all completed and monitored and ready for use by SMEs. We expect this number to increase significantly over the next number of months as the centres that have finished recruiting will now focus on completing data on those already recruited. Both SMEs have significantly furthered the development of the two tests and are continually optimising and refining the process.
This study had the benefit of two forms of monitoring. Study monitoring was conducted by clinical trials unit (CTU), Copenhagen and data monitoring conducted both in an onsite capacity and oversee by the Global Clinical Monitor (GCM) based at sponsor site (UCC). Each site had an initial visit by both CTU which confirmed that the site was ready to commence recruitment. CTU also completed two further visits as the study progressed. The GCM visited each site once they had completed a number of both compulsory visits. The purpose of this visit was to assess the work of the research midwives and to observe how the study was advancing locally. This visit helped identify local issues and allowed the GCM to discuss specific challenges that were facing the research staff.
Local data monitoring entailed weekly checking of source data against online database as well as checking of consent forms. Each site has a local data monitor but this is a duty they do as an extra to their other roles within the study. The GCM monitors non-source data for all sites as frequently as she possible can. She also is the local data monitor for sponsor site. This data monitoring task allows for consistent data entry throughout each site and reduces the risk for data entry errors. The result now seen in 3rd period is ‘clean’ data with a minimal backlog of data awaiting entry. This allows study to proceed with data export on those study participants that have completed data.

Work is continuing on the development of the biobank governance structure as we move into the 4th period and this will involve with input from the steering committee, the SAB and the EAB.

Further research on the statistical and health economic analysis plans has been carried out so as to be ready when the necessary data is available for ProTest and MetTest.

Dissemination activities have been progressing well on in the project. These ongoing activities include international presentations on IMPROvED, media coverage through radio, television and newspaper, and the use of social media.
Each of these raise the public awareness of the study increasing engagement, interest and activity on the project. These activities continue to remain a vital component for the IMPROvED as the 4th period is entered.

Potential Impact:
IMPROvED aims to develop a clinically useful screening test for pre-eclampsia which will enable identification in early pregnancy of women at risk of pre-eclampsia, and thus allow closer prenatal monitoring, early diagnosis, and timely intervention. Conservative estimates suggest that the appropriately targeted use of existing therapies (such as low dose aspirin) should reduce the overall incidence of pre-eclampsia by approximately 20%, but importantly with a greater reduction in early onset disease (30%). The reductions in the incidence of pre-eclampsia, particularly in early onset disease, will lead to reduced intrauterine, neonatal, childhood and long-term complications for babies. An effective screening test would facilitate stratification and targeting of limited resources within healthcare systems and economic assessments of screening for pre-eclampsia have consistently found that screening for pre-eclampsia is cost-effective under various scenarios.

Dissemination activities will lead to greater awareness of the risks of pre-eclampsia and will foster a culture where open discussion is encouraged. Members of the PAB have reported that in certain instances maternity care givers do not discuss pre-eclampsia with pregnant women as they feel it will frighten/stress the women. However other members have reported the effectiveness of open discussion and in the Netherlands all pregnant women are supplied with a leaflet from the Dutch patient group containing pre-eclampsia information. In addition, the availability of a reliable predictive screening test early in pregnancy should encourage maternity care givers to speak more freely about pre-eclampsia.

The residual IMPROvED biobank housed in UCC will be a valuable future resource for pregnancy researchers who would not normally have access to samples from large cohorts of patients. The precursor to IMPROvED, the SCOPE (Screening for Obstetric and Pregnancy Endpoints) study biobank (http://www.scopestudy.net/) is still providing samples to international researchers. Therefore we expect that the IMPROvED study will lead to an expansion in pregnancy research resulting in greater understanding of pregnancy complications and potential strategies to combat these complications.

List of Websites:
www.fp7-improved.eu

Reported by

UNIVERSITY COLLEGE CORK, NATIONAL UNIVERSITY OF IRELAND, CORK
Ireland
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