Wednesday, May 1, 2013

The April 2013 ECFS CTN Newsletter

Year 5 Issue 1

ECFS-CTN at present

The ECFS-CTN has entered its fifth year of activity and it is now one year since it has expanded from 18 to 30 sites across 11 countries in Europe (See the complete list of ECFS-CTN Sites here)

There are currently 15 active studies in the network and 10 protocols were reviewed in 2012. There were 8 active studies by the end of 2011 and 5 protocols were reviewed in 2011. Thirteen studies are pharma sponsored trials and two are multinational investigator initiated trials. It is becoming more frequent to have studies reviewed at an early stage and comments of the Protocol Review Committee are taken into account in revised protocols. An overview of ongoing and completed CTN studies (with results when available) can be found at the website here

There was no renewal of the Executive Committee in 2013 which is composed of Isabelle Fajac from Paris (CTN Director), Carlo Castellani (Verona), Nico Derichs (Berlin), Pavel Drevinek (Prague), Tim Lee (Leeds) and Luisa Pereira (Lisbon). Andreas Reimann is the representative of CF Patients Organizations and Anil Mehta liaises with the European CF Registry. Carlo Castellani was co-chair during 2012 and we all thank him for his valuable input! Tim Lee has since taken over the role of co-chair. Nico Derichs has replaced Harm Tiddens as the liaison with the CFF-TDN and we would like to extend our thanks to Harm for having conducted this role since the beginning of the ECFS-CTN! In 2014, 3 new members for the Executive Committee will be needed and applications will be sought for in Autumn 2013.

ECFS-CTN steering committee meeting and CF-related meetings in Paris in January 2013

Representatives from all CTN sites and committees have met in Paris on the 24th and 25th January 2013 for the winter meeting of the ECFS-CTN steering committee. An update of the main topics that were discussed are given in this newsletter.

The ECFS Board, the ECFS Patient Registry and representatives of European CF patient organizations organized meetings in parallel at the same location. This was an excellent opportunity to see all people together and to discuss common subjects and ways of cooperation.

As discussed in the previous newsletter, the ECFS-CTN has decided to involve patients in protocol review. This allows sponsors to have feedback from those who are actually involved and have knowledge based on experience. A face-to-face meeting took place in Paris on the 26th of January to train the patients who have agreed to be involved in protocol review. Eleven patients attended the meeting which covered general information about the ECFS-CTN, different aspects of clinical trials, the different chapters of a study protocol and the list of questions that will be asked when they evaluate a protocol. It was a very lively and inspiring experience for all present. Patients who couldn't attend the meeting will be trained using written documentation and teleconferences.

We thank Vaincre la Mucoviscidose (the French CF association) for their logistic support of this meetings!

Investigator-Initiated Trial

The ECFS-CTN wants to develop an Investigator-Initiated Trial. In 2011, sites were asked to name topics of interest. Working groups began working on draft protocols for the two topics that were selected during the steering committee meeting in Dublin in June 2012. Feasibility checks were run in the network during the summer 2012 and protocol outlines were drafted.

At the steering committee meeting in Paris last January, the topic that was most favoured by sites was the eradication of Methicillin resistant Staphylococcus aureus (MRSA). Indeed, it is usually thought that MRSA in CF should be treated and that early aggressive treatment of new infection to eradicate the pathogen should be instituted. However, the optimal eradication protocol isn't known and evidence-base is required to robustly guide clinical practice. It was decided to set up a small steering group of experts to write a full protocol that will be discussed at the next ECFS-CTN steering committee meeting in Lisbon in June 2013.

Outcome parameters

Standard Operating Procedures for many outcome parameters are available on the intranet or upon request to the ECFS-CTN coordinating center. The Standardization Committee is now working on site training for CF-specific outcome parameters and certification of sites.

The first manuscript on clinimetrics on CFTR biomarkers was published in the European Respiratory Journal last January ( More manuscripts on clinimetrics to review the evidence for the out-come measures used in the CF field are in the final stage before submission for publication. These are on inflammatory markers, on lung clearance index (LCI) and on microbiological definitions.

The ECFS-CTN wants to provide evidence-based knowledge to use new surrogate endpoints. These new outcome parameters should be useful to detect early lung disease. LCI and chest Computed Tomography (CT) have been chosen as the most promising new outcome measures in that respect. For LCI, a standard technique for ECFS-CTN studies was selected and will be implemented in interested ECFS-CTN sites for use in clinical trials. A central reading and expertise center will be set up. For chest CT, following a survey in 2012, 15 ECFS-CTN sites qualified for participation to the SCIFI-CF network : "A standardized, ECFS-CTN chest imaging framework for interventions and personalized medicine in CF". This network aims at setting-up a chest-CT network for standardization of technique, central reading and storage. Standardization and training of sites selected to participate to the SCIFI-CF network will occur in 2013. The ECFS-CTN will also work towards having LCI and chest CT approved by the European Medicines Agency (EMA) for use as surrogate outcome parameters in clinical trials.

A workshop on endpoints for cystic fibrosis clinical trials took place in September 2012 at the EMA. It gathered experts in the field of CF (all belonging to ECFS-CTN), European drug regulators, representatives of pharmaceutical companies and one patient representative. Current scientific evidence on outcome measures for evaluating medicines targeting CF lung disease, bronchopulmonary infection and exocrine pancreatic insufficiency were discussed and compiled. Areas in need of further research and education were identified. The summary of the meeting can be viewed on :

Quality and training

Quality in the ECFS-CTN is of the utmost importance. Since 2013 is already the fifth year of ECFS-CTN activity, it is felt that time has come to begin monitoring quality. For a network of sites dedicated to clinical trials, it appears that there are 2 aspects of quality:

  • quality in clinical research : procedures to evaluate site participation and performance should be worked on in order to monitor fairly. Indeed, the monitoring system will have to take into account the diversity of regulations and processes of the different European countries involved in the ECFS-CTN
  • quality in communication within the network : accurate and timely communication between sites and the Coordinating Center is indeed critical for a network

Monitoring quality within ECFS-CTN will be implemented step by step in the coming months and discussed at the steering committee meetings. It is planned that each site will receive once a year its own quality report.

In parallel with monitoring quality, it is necessary to hold some tools for sites to improve quality. The CFF-TDN has developed a Quality Improvement Program and has offered to share it with the ECFS-CTN. The Training Committee is in the process of getting familiar with the CFF-TDN Quality Improvement Program and discussing how it could be implemented in the ECFS-CTN.

Communication towards Patients

The ECFS-CTN works closely with the Patient Organisations which were involved from the start of ECFS-CTN and take part in the steering committee meetings and the Executive Committee. Moreover, European National CF Associations financially support the ECFS-CTN. A report has been written in 2012 for Patient Organisations to summarize the ECFS-CTN activities. It is planned to write such a report each year.

The ECFS-CTN has developed in 2011-2012 a brochure for patients on clinical trials and it is available on the ECFS-CTN website in 10 languages (available here). In 2012, the ECFS-CTN has also worked towards communication with children and a short brochure for children has been developed with drawings. It is being translated and it will be shortly available on the ECFS-CTN website.

All ECFS-CTN sites are proud to be part of the network and in order to make the patients of the CF centers aware that their center is part of the ECFS-CTN, posters for adult and children centers were drafted and translated. They will be sent to all ECFS-CTN sites.

The full Newsletter in PDF format can be found here