• Challenges and opportunities of conducting clinical trials in paediatrics

• Management of thalassaemia and haemoglobinopathies: an ongoing challenge

The meeting was aimed to raise the attention on the progresses achieved by the clinical research and the challenges to be faced in conducting clinical trials in paediatrics, also highlighting the importance of the international cooperation through European Networks and the global initiatives to create synergies and foster clinical research. The second session was more focused on the new pathways and therapeutic strategies for the management of thalassaemia and haemoglobinopathies and was the occasion to talk about the goals of the DEEP project.

The abstract of the first session are available at the dedicated page.

The abstract of the second session are available at the dedicated page.

Here you can also download the DEEP Open Meeting brochure, which can be browsed even through mobile devices.

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.

In particular, CRAs and PIs highlighted the strengths and weaknesses encountered in the study conduction with particular reference to the following issues:

• Informed consent procedure

• Planning study visits

• IMPs handling

• Dose adjustments for Safety and Efficacy reasons

• Periodic assessments for Safety

• Data entry in e-CRF

• Collection of Ferritin Samples for centralized evaluations and MRI Scans

• Study documentation

• Pharmacovigilance

• Monitoring activities.

The gathered information have provided updated information on all the centres involved in the study and are essential to identify the main issues to be solved to increase the effectiveness of the study and to ensure patients’ safety and high quality of collected data.

It is a promotional teaser video describing with an “emotional” cut and a dynamic style, scope and objectives of the project through the voice of scientists, patients and the management team, focusing on the prospects for an enhancement of the patients’ quality of life.

It includes touching moments resulting from the personal and direct experiences of children affected by thalassaemia, who were interviewed in May 2015 in Tirana with the collaboration of University Hospital Center “Mother Teresa”– UHCT (Albania), reporting their situation, describing how their diseases are affecting their daily life and how they live with their disease.

The DEEP Project has entered in their homes and in their private lives, and it has given us the possibility to understand how we can really support them and how clinical studies can definitely help in finding a suitable cure.

Enjoy the DEEP Video.

After the sad decision to cancel the General Assembly Meeting in Tunis, due to the disorders which have occurred across the country, the 7th DEEP General Assembly (GA) will take place in Padua (Italy) on April 13th -15th, 2016 with the participation of the whole DEEP Consortium as well as of external experts.

Here you can find the final agenda of the Meeting, which can be browsed even through mobile devices.

The meeting will be focused on a general update of the project’s activities, the progresses and achievements of the DEEP project as well as the finalization of the DEEP-2 and DEEP-3 studies, that are of utmost priority. Among others, the financial resources reallocation according to the recruitment performance at any involved centre will be discussed during the meeting.

In the same context of the GA meeting, the DEEP-2 Investigator Meeting and the 4th Open Meeting will take place.

In particular, the Scientific Open Meeting on April 15th, 2016 will entail two sessions:

   –  Challenges And Opportunities Of Conducting Clinical Trials In Paediatrics

   –  Management Of Thalassaemia And Haemoglobinopathies: An Ongoing Challenge

The Scientific Open Meeting will be the occasion to raise the attention on the progresses achieved by the clinical research and the challenges to be faced in conducting clinical trials in paediatrics, also highlighting the importance of the international cooperation through European Networks and the global initiatives to create synergies and foster clinical research. The second session will be more focused on the new pathways and therapeutic strategies for the management of thalassaemia and haemoglobinopathies and will also be the occasion to talk about the goals of the DEEP project.

More details on the event and the final agenda are available here and through our social network channels (Facebook and Google+).

Moreover, Dr. Giannuzzi highlighted how this lack of harmonisation makes more difficult the approach in case of studies involving non-EU Countries, as DEEP, and especially ‘small populations’, such as children and patients affected by rare diseases, which typically are multi-centre and multi-national.

More details on the event and the list of all submitted abstracts are available here.

They have highlighted the progresses achieved by the clinical research in Albania so far and the importance of a more tight international collaboration within the European Networks to create synergies to spread excellence and attract European funding.

In particular, Donato Bonifazi explained that the DEEP-2 Safety/Efficacy Study represents the first paediatric clinical trial ever performed in Albania, currently enrolling patients. Beyond the administrative management of the study, the Italian Sponsor is extensively supporting the Albanian study team both in the start-up phase and in the trial progression, ensuring the performance of the trial in compliance to the ICH GCP. This represents a valid example of how to respond to European Commission (EC) Research policies promoting networking and public-private partnership, providing a new model for clinical research and disseminating competencies and technologies in non-European Countries.

The model proposed by DEEP focuses on therapeutic needs in paediatric and the integration of research and culture, adopting a global regulatory framework and patient-tailored transparent communication tools and has to become an example and the first milestone in developing the clinical research in Albania.

The videos of their interviews are available at the DEEP YouTube channel.

Donato Bonifazi, DEEP Project Manager presented the project in the context of the international paediatric trials that have to face a default level of complexity, due to regulatory, methodological, ethical and administrative issues, especially when they are registrative and international as DEEP is.

In particular, the specific challenges that DEEP has addressed and is still facing with reference to the recruitment and patient’s retention have been described, since DEEP is a ‘Registrative’ CTs with economic burden, ethical stringent provisions and GCP-ICHE11 obligations that involves not only a paediatric multi-ethnic population with different cultures, laws and children of different ages but also a rare and disperse population involving different Rare Congenital Anaemia.

Moreover, the DEEP multisteps strategy to address these issues has been presented, resulting from the following key aspects:

• the organisation of a ‘trials management plan and infrastructure’ including SOPs preparation, data management, drug management, pharmacovigilance, monitoring, etc;

• the implementation of a unique procedure and a unique CTA ‘package of documents’;

• the developments of a ‘patients tailored approach’ including children, families and association.

To conclude Donato Bonifazi updated on the patients’ recruitment that is currently proceeding successfully thanks to a continuous and coordinated activity of the TMT and the PIs and the continuous discussion of the Protocol-related issues among Principal Investigators, Trial Management Team and all the study key contacts that has led the inclusion of many new centres.

The event was also the occasion to discuss, in the framework of an international multi-stakeholders debate, the present and the future of the paediatric research including the efforts made by the scientific community and the ongoing projects such as the proposed Paediatric Research Infrastructures (EPCTRI) and the global networks.

The report provided a comprehensive overview of the activities performed with particular reference to the implementation of the DEEP studies in compliance with the Paediatric Investigation Plan (EMEA-001126-PIP01-10), as approved and further amended by the Paediatric Committee (PDCO).

The main efforts of this reporting period have been devoted to implement DEEP 2 recruitment and study conduct. In particular, in order to reach the required patient number, the number of clinical centers has been increased, recruitment capacity has been checked and study qualification visits have been performed.

As stated in the report, even if the main project activities have been completed and the great majority of the deliverables and milestones foreseen for that period have been addressed, many delays have occurred mainly due to the lengthy approval process imposed by many local ethics committees and competent authorities. These problems have led to a request of amendment of the DEEP Grant Agreement, which has been approved on 10.06.2015 by the European Commission providing an extension of 20 months of the project. The specific reasons for requesting this extension have been:

• prolonged difficulties due to the political instability in two of the North African countries, Egypt and Tunisia, which were representing over 50% of the total potential patients recruitment;

• need to identify new recruiting centres;

• changes in Regulatory Procedures for authorisation of the studies in different countries;

• changes in the DEEP 2 study protocol as included in a modified agreed PIP.

Furthermore, DEEP has also faced many regulatory issues that led on 26/08/2014 (following a Letter of intent on June 2014) to a request for modification (RfM) of the agreed PIP to the European Medicines Agency (EMA) and its Paediatric Committee (PDCO). The procedure ended on 17/11/2014 as described in the figure below.

The PIP modification was motivated by the need to implement the results of the modification introduced by the scientific coordination group into the DEEP 2 protocol as well as it was intended to clarify minimal aspects on timing and use of data with reference to DEEP-1 and DEEP-3 studies. In this context and to create the conditions for operating according to the European ethical and regulatory legislation, the DEEP Coordinator has developed specific standard operating procedures (SOPs) and guidelines to be implemented by all DEEP Beneficiaries.

As a result, the DEEP project’s commitment of operating according to the European ethical and regulatory legislation has ensured and will still guarantee the implementation of ethics principles and GCP recommendations in all participating centres, including those located outside the European area, thus promoting the spread of such practices in clinical research.

The report covers the period from 01/01/2011 (project start date) to 31/12/2013 and takes into consideration that DEEP, originally planned as a 4 year project, has faced three amendments of the Description of Work with prolongation of the project for 20 months. Although have produced delays in the start-up of the clinical studies and related tasks, these changes have been considered as highly justified and will improve the output and impact of the DEEP project. Indeed, the major delays in DEEP project during the last years were related to the requests of changes in the PIP and long lasting ethical approvals. So, now that the majority of centres have already received the approvals for the clinical trial it should be easier to continue with the related tasks.

It was particularly highlighted that the DEEP project has made sufficient progress and is ready to reach the goals and to contribute to the improvement of the clinical management of children with transfusion-dependent thalaessemia and other hemoglobinopathies who need chelation therapy. The whole project and the individual workpackages have been making satisfactory progress, as well as results of this study provide scientific evidence that the dosage of deferiprone used in adults can be effective also in small children.

Regarding the recruitment rate, Dr. Plaseska-Karanfilsk stressed that the measures undertaken by the Project Management Team (PMT) have been successful and that DEEP-2 and DEEP-3 studies have been recruiting patients with an increasing rate, ensuring that the objectives could be reached by the end of the project.

The expert continues encouraging the project Partners to strengthen the efforts towards recruiting increasing number of patients in the DEEP-2 and DEEP-3 studies in order to ensure finalization of these clinical studies which are very important for the overall success of the DEEP project.

One further positive evaluation was referred to the DEEP Consortium consisting of strategic partners with specific expertise in hemoglobinopathies and paediatric clinical trials design and managements, regulatory aspects and ethic issues. The complementarity has been well appreciated as regards to expertise and resources within DEEP Consortium and the balance achieved also with reference to geographical spread across the Mediterranean region with the highest incidence of thalassemias.

The report was concluded with a note regarding the dissemination activities and all Partners were inviting to publish the project results in peer reviewed papers.