The meeting provided an update on the achievements and difficulties encountered toward the implementations of specific project tasks, the reasons for some delays and the mitigation strategies set into place in order to overcome such obstacles.

The meeting opened with a comprehensive overview of the activities performed and the most important achievements carried out, with particular reference to the implementation of the DEEP studies in compliance with the Paediatric Investigation Plan – PIP (EMEA-001126-PIP01-10), as approved and further amended by the Paediatric Committee (PDCO). In particular, the main efforts carried out to implement DEEP-2 recruitment and study conduct were highlighted, that have led to an increase of the number of clinical centres, the check of the recruitment capacity as well as the organisation of study qualification visits.

Moreover, an update of the clinical studies has been provided, with a particular focus on:

• the difficulties to conduct the DEEP-2 trial that has to face a default level of complexity, due to regulatory, methodological, ethical and administrative issues;

• the status of DEEP-3 Study and its updated results;

• the updated overview of the pharmaco-economic study.

Among others, the financial resources reallocation according to the recruitment performance at any involved centre have been discussed during the General Assembly meeting.

The second meeting day provided an update on DEEP-2 study protocol and procedures and was characterised by the organisation of the DEEP-2 Investigator Meeting, held as a guided roundtable where CRAs and Principal Investigators from main recruiting sites have presented and discussed the strengths and weaknesses of their own center.

In the same context of the GA meeting, the 4th Scientific Open Meeting took place on April 15th, entailing two sessions:

-Challenges and opportunities of conducting clinical trials in paediatrics

-Management of thalassaemia and haemoglobinopathies: an ongoing challenge

The meeting represented an excellent opportunity to foster fruitful scientific debates and exchange information. Advancement in the work packages and partner involvements were discussed in order to build a perfect working basis for the forthcoming activities.

All the presentations of the 7^th General Assembly meeting can be downloaded from the “Presentations” dedicated page.

All the abstracts of the DEEP Open Meeting can be found in the dedicated brochure, which can be browsed even through mobile devices.

The DEEP-2 study actually involves a total of 227 patients included in 32 recruiting centres: Italy (51), Egypt (123), Greece (9), Albania (25) Tunisia (7) and UK (10). The first nine patients have been enrolled in UK and 10 in Tunisia this week. The enrollment will terminate when 344 patients will have been randomized.

Further 5 new centres in Turkey (Hacettepe University, Faculty of Medicine in Ankara; Istanbul University, Cerrahpaşa Faculty of Medicine in Istanbul; Kanuni Sultan Suleyman TRH in Istanbul; Mersin University Faculty of Medicine in Mersin; Akdeniz University Medical Faculty in Antalya), 1 in Lebanon (Nini Hospital in Tripoli), 1 in Albania (Hospital ‘Ihsan Çabej’ in Lushnjë) and 1 in Qatar (National Center for Cancer Care and Research in Doha) have been contracted and are very close to recruit their first patients. The centers in Cyprus and Morocco are waiting for the last authorization before they can be activated.

In order to ensure the correct implementation of study protocol and speed up the recruitment phase, the DEEP Management Team has issued a new version (2.0) of the Study Procedure Manual both in PDF format and hard copy to be sent to each site. This version is specifically addressed to the clinical investigators aiming at facilitating consistency with protocol implementation among study sites and to be an on hand reference to solve doubts/questions that may arise during the study conduction.

Moreover, all PIs regularly receive a monthly DEEP-2 study newsletter with an update of the patients’ enrolment and the FAQ section, available on the website, aimed at clarifying most of the criticisms of the study protocol.

Stay connected with the DEEP website and social networks (Facebook and Google+) and look at the counter on the homepage to be updated on the DEEP-2 patients recruitment status!

On October 2015, 283 patients (86% of 328 subjects of the study population) were enrolled, 36 of which are currently in the prospective phase of the study. The observation, which aims to investigate serious and non-serious adverse reactions, as well as risk factors for ADRs related to deferiprone treatment, has ended for 166 patients. The mean observation time per patient was currently 2.1 years, with 595 person-years (84% of 711 person-years).

To date, the study is in the last collection episode for most of the centres involved (Tirana, Nicosia, Bari, Naples, Padua, Palermo and Florence) that will be closed for recruitment soon. The prospective arm of the study will be concluded in October 2015, while retrospective data will be collected until termination of the study with reference to the same period (up to October 2015).

Recently the study successfully received the ethical approval for two new centres in Casablanca (Hôpital 20 août and Hôpital Universitaire d’enfants Abderrahim Harrouchi) and the recruitment started at Centre National de Greffe de Moelle Osseuse (CNGMO) of Tunis.

Furthermore, the DEEP-3 Study Team is currently in the process of including two new centres in Egypt: Alexandria and Zagazig.

Principal Investigators (PIs) are still working to continue the enrollment of patients within the DEEP-2 study and to date a total of 117 patients have been already included in 12 recruiting centres: Italy (43), Egypt (53), Greece (6), Albania (15). Further 2 centers are very close to recruit their first patients and 10 recruiting centres are still waiting for receiving the approval/Site Initiation Visit. In order to be sure to reach the planned number of patients, 3 new centres in Turkey (Hacettepe University, Faculty of Medicine in Ankara; Istanbul University, Cerrahpaşa Faculty of Medicine in Istanbul; Kanuni Sultan Suleyman TRH in Istanbul), 1 in Lebanon (Nini Hospital in Tripoli), 1 in Albania (Hospital ‘Ihsan Çabej’, Lushnjë) and 1 in Qatar (National Center for Cancer Care and Research, Doha) are being activated.

Total number of centers will then be 30.

Stay connected with the DEEP website and discover the counter on the homepage to be updated on the DEEP-2 patients recruitment status!

This event represents an important step both for the study, with the recruitment of the first paediatric patients in Albania in a not-for-profit study, but also for the patients themselves, having the chance to be undergone to a diagnostic procedure, which is, today, deemed necessary from major European guidelines and not currently available in-house.

 Albania – Tirana is ready to enrol its first patient

The University Hospital Centre “Mother Teresa” of Tirana (Albania) has received the Site Initiation Visit (SIV) on March 18th, 2015, and is ready to begin the patients’ enrolment.

 Cyprus – Waiting for final approval from National BioEthics Committee

The Department of Medical and Public Health Services of the Ministry of Health of Nicosia (Cyprus) is waiting for the final approval from National BioEthics Committee. The auditing of the documents and the answers, required by the Ethics Committees, were mainly focused on the informed consent and the management of contraception for patients of childbearing age in the study.

 Egypt – Cairo is ready to enrol its first patient, authorization process ongoing for Alexandria and Zagazig

The Cairo University Faculty of Medicine has received the site initiation visit (SIV) on March 2nd, 2015 and has already enrolled its first patient into the study, while the Alexandria University Hospital and the Zagazig University Hospital Haematology outpatients Clinic, are both in process of sending the submission package to the Ethics Committee and the Competent Authority.

 Greece – Athens is ready to enrol its first patient

Agia Sofia Children’s Hospital of Athens (Greece) has received the Site Initiation Visit (SIV) on April, 3rd  2015, and is now ready to begin the patients’ enrolment.

 Italy – First patients enrolled in Italy

So far, 8 Italian centres (Bari, Cagliari, Cosenza, Napoli, Padova, Palermo Civico, Palermo Cervello, Sassari) have already started the patients’ enrolment.

 Lebanon – Start submission to Ethics Committee and Competent Authority

The Nini Hospital centre, located in Tripoli (Lebanon) is in the process of sending the submission package to the Ethics Committee and the Competent Authority. The Centre estimates a potential number of 30 patients to be enrolled.

 Morocco – Start submission to Ethics Committee and Competent Authority

The Hopital 20 Aout, and the Abderrahim Harouchi Children Hospital CHU Ibn Rochd of Casablanca (Morocco) are both in the process of sending the submission package to the Ethics Committee and the Competent Authority.

 Turkey – Start submission to Ethics Committee and Competent Authority

The 3 new centres involved in the study: Hacettepe University Faculty of Medicine Child Health and Disease Hospital (Ankara), the Istanbul University, Cerrahpasa, Medical Faculty/ Paediatric Haematology Hospital (Istanbul) and the Mersin University Faculty of Medicine Child Health and Disease Hospital (Mersin), are all in the process of sending the submission package to the Ethics Committee and the Competent Authority. The three Centres estimate an enrolment of approximately 80 patients in total.

 United Kingdom – Waiting for final approval from Competent Authority MHRA

UK has received a favorable opinion from the MHRA, which will become effective when the amendment to the protocol will be presented. This amendment has already been approved by the Coordinating Ethics Committee of the Study, and is ready for the submission to both MHRA and REC. The auditing of the documents and the answers, required by both the Ethics Committees and Competent Authorities of UK, were mainly related to the informed consents and the management of contraception for patients of childbearing age enrolled into the study.