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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PIBD-SETQuality (Paediatric Inflammatory Bowel Diseases Network for Safety, Efficacy, Treatment and Quality improvement of care)

Teaser

Summary

The incidence, particularly of paediatric onset Inflammatory Bowel Diseases (PIBD, Crohnâ€™s disease (CD) and ulcerative colitis (UC)) has risen dramatically in recent decades. A significant research gap at present involves identification of strategies to maximise therapeutic effectiveness without increasing risks from the treatment. The major goal of this proposal is the
1) Development of an accessible and feasible risk-stratified treatment algorithm for new onset paediatric IBD (based on an existing inception cohort) and validation of this algorithm in a new independent inception cohort
2) Generation of a homogenized high-powered and secured data base to collect and analyse longterm real world data of children with IBD (inception cohort) in a prospective registry designed to analyze effectiveness and safety signals and correlate them to individual risk factors (genetic, immunological and microbiological)
3) Design and performance of a risk algorithm-based prospective large-scale multicenter randomized clinical trial (RCT). For the first time a RCT will be based on a stratification of patients into high versus low risk groups for early complicated/relapsing disease based on predictors at presentation in order to provide optimal therapy (further optimized by drug monitoring), and using different treatment strategies in each arm

Work performed

To address the specific aims of this project three approaches devided into 11 work packages ( plus 2 WP on project management and publication/communication/dissemination) were designed :
The search for risk factors for severe diseae evolution in existing or historical patient cohorts of CD (WP1) and UC (WP2) is completed and underway for final validation allowing to create disease specific risk algorithms.
Hugh amount of preparationary work was invested in the organization of the randomized controlled clinical trial (RCT, WP3) with integrated pharmacological analyses (WP4), health economic analyses (WP8) and microbiological analyses (WP10). Complete clearance/authorisation of the final protocol version 3 was obtained Q3 2016 allowing to finalize the electronic case report form (eCRF) and data management tool as well as the logistic infrastructure (shiping of samples to different laboratoires for analyses (WP4, WP9,WP10) by Q4 2016. The development of the eCRF was performed in time by partners 2 (SZMC) and 9 (PIBDnet). The eCRF with integrated randomisation is fully functional since Q4 2016 allowing recruitment of the first patient Q1 2017 (first patient included in France in February 2017). The delay between the expected and real inclusion of the first patient (scheduled for Q4 2016) was 4 months. These modifications gave the possibility to add an annex study to the initial protocol allowing to include patients that experience a relapse during the RCT with a step-up treatment approach (cf version 3 of the protocol). By June 2017 several sites are open for recruitement of patients to the RCT in FR, IT and DE; sites in NL, UK, BE, CAN and ISR are expected to have ethical and legal clearance allowing to start recruitment in Q4 2017, PO, ES and CZ are expected to follow Q4 2017. By June 30th 2017, 7 patients were included and randomized in this RCT. The overall coordination of this RCT is assured by partner 9, PIBDnet, allowing to recruit clinical investigators of PIBDnet, who are not partners of this H2020 project as third parties.
The logistics for sampling and performing the pharmacological analyses within the RCT (WP4) are completed and fully functional. The Health economic and quality of life questionnaires (WP8) are validated and added to the RCT (Q4 2016).
WP5 is dedicated to the creation of a patient reported outcome parameter (PRO), allowing to measure the response to therapy based on the patientâ€™s subjective impression. This WP takes advantage of an ongoing project outside this H2020 project lead by two PIBDnet PIs, Drs Dan Turner (ISR) and Antony Otely (CAN). The phase 1 of this work includes Concept Elicitation Interviews and is almost complete (Q2 2017).
A prerequisite for the generation of a longitudinal inception cohort (WP7) is a highly secured and stable IT system (WP6). The planned PIBD Cloud database (designed by partner 10 (AIMES)) is fully functional and under use since Q1 2017. Similarly to the RCT, the authorization process and ethical clearance (coordination partners 3 and 4 QMUL, ERASMUS) took a little longer as initially expected but was complete in the NL by Q4 2016 allowing to recruit the first patient into the inception cohort in the January 2017. The delay between the expected and real inclusion of the first patient (scheduled for Q2 2016) was 6 months. By June 30th 2017, 14 patients were included into the inception cohort. A subgroupe of patients in this inception cohort will have additional sampling (WP9,10), the SOP and selection of biomarkers are finished for WP9 and 10, however, since patient recruitment just started these analyses did not start yet (as per initial plan). Similarly, for the genetic analyses (WP11) of patients developping rare complications, the methods (exome sequencing) are fully established and functional in the lab (partner 1, UDP), however, as per initial timing, the analyses did not yet start, since a sufficient number of patients needs to be obtained. Analyses are sc

Final results

All preliminary steps are settled for this project and patient recruitement started to the RCT and to the inception cohort, however, results of the studies will be only available at the end of the inclusion/ follow-up period of the studies.
The following important potential impacts form PIBDSetQuality are expected :

Significantly decreasing treatment related risks (infections, new immune-mediated diseases and tumours/cancers) in the paediatric population

Establishing novel and/or more effective treatment schemes for healthcare interventions in the paediatric population
In summary, focussing PIBD-SETQuality on PIBD patients targets the most severe patients early in their lives and disease progression and can lead to major benefits in the short, medium and long term.
1. Individual benefits: Identification and improved treatment of patients at most risk of severe disease progression will have major impacts on improved health, well being, and quality of life of the individual. These will be demonstrated within both the RCT and the registry data.
2. The families: Improved health for an individual also benefits their family both in terms of psycosocial and economic outcomes, by the ability to lead â€˜normalâ€™ lives, retaining full employment and reducing stresses.
3. There is an positive impact to the local health economy by identifying effective and safe treatments directed at the patients who will most benefit from them with improved utilisation of scarce resources. This is a direct benefit translatable across all of Europe and beyond.
4. Educational achievement and job prospects are improved. By improving health and reducing side effects of treatment leads to improved school attendance, educational achievement and job prospects. This will benefit the broader economy in the long term by improving the productivity of the patients and their carers.