Guideline on the design and conduct of cystic fibrosis clinical trials: The European Cystic Fibrosis Society–Clinical Trials Network (ECFS-CTN)

Department of Pediatrics, University Hospital of Leuven, Leuven, Belgium.
Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society (Impact Factor: 3.48). 06/2011; 10 Suppl 2:S67-74. DOI: 10.1016/S1569-1993(11)60010-6
Source: PubMed


We describe the rationale for disease specific research networks in general as well as the aims and function of the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) specifically. The ECFS-CTN was founded in 2009 with the aim of improving the quality and quantity of clinical research in the area of cystic fibrosis (CF) in Europe. A network of 18 clinical trial sites in 8 European countries was established according to uniform state-of-the-art quality criteria. To support the ECFS-CTN in the acquisition, planning and conduct of clinical trials, the network is equipped with a coordinating centre, steering and executive committees, and committees for protocol review, standardization, training and networking as well as a data safety monitoring board. A strong partnership with European CF patient parent organizations aims to increase awareness of the need for efficient clinical research and the participation of patients in clinical trials.


Available from: Steven Conway, Jul 29, 2014
Journal of Cystic Fibrosis Volume 10 Suppl 2 (2011) S67–S74
Guideline on the design and conduct of cystic fibrosis clinical trials:
The European Cystic Fibrosis Society–Clinical Trials Network (ECFS-CTN)
K. De Boeck
*, V. Bulteel
, H. Tiddens
I. Fajac
, F. Dufour
A.R. Smyth
on behalf of all ECFS-CTN network partners
University Hospital of Leuven, Leuven, Belgium
Erasmus Medical Centre , Rotter dam, The Netherlands
J ohann Wolfgang Goethe-Universität, Frankfurt/Main, Germany
Université René Descartes, Paris, France
St. James University Hospital, Leeds, United Kingdom
Vaincre la Mucoviscidose, Paris, France
Division of Child Health, University of Nottingham, Nottingham, United Kingdom
Epicime, CIC 201, RIPPS, Hôpital Femme Mère Enfant HCL & Université de Lyon, Lyon, France
Belfast City Hospital, Belfast, UK
We describe the rationale for disease specific research networks in general as well as the aims and function of the European Cystic Fibrosis
Society–Clinical Trials Network (ECFS-CTN) specifically. The ECFS-CTN was founded in 2009 with the aim of improving the quality
and quantity of clinical research in the area of cystic fibrosis (CF) in Europe. A network of 18 clinical trial sites in 8 European countries
was established according to uniform state-of-the-art quality criteria. To support the ECFS-CTN in the acquisition, planning and conduct of
clinical trials, the network is equipped with a coordinating centre, steering and executive committees, and committees for protocol r eview,
standardization, training and networking as well as a data safety monitoring board. A strong partnership with European CF patient parent
organizations aims to increase awareness of the need for efficient clinical research and the participation of patients in clinical trials.
© 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserv ed.
Keywords: Research network; Clinical trials; Cystic brosis
1. Introduction
The Clinical Trials Subgroup of EuroCareCF Workpackage
3 (Coordination of Clinical Research) held meetings to discuss
the best strategy to design and implement clinical trials in the
area of new therapies for cystic fibrosis (CF) patients. These
discussions endorsed the need for a disease specific clinical
trials network in Europe. This document explains the need
for and formation of the European Cystic Fibrosis Society
Clinical Trials Network (ECFS-CTN).
* Corresponding author: Kris De Boeck, Department of Pediatrics, Uni ver-
sity of Leuven, Herestraat 49, 3000 Leuven, Belgium. Tel.: +32 16 343831;
fax: +32 16 343842.
E-mail address: (K. De Boeck).
1569-1993/$ - see front matter © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
1.1. Rationale for a CF Clinical Trials Network
A recent review lists all studies on survival and mortality
reported from CF registries [1]. Even with the best possible
care, the median survival of subjects with CF is only about 36
years of age. It should be emphasized that the median age of
survival is a statistical prediction made for a specific birth co-
hort. In all CF patient registries the current median age at death
is at least 10 years younger than the calculated median life
expectancy so that the current median age at death is only about
25 years. This crude reality is insufficiently reported. Against
such a background of premature mortality it is obvious that
research into new treatments and especially treatments with
“disease modifying drugs” might bring major improvement in
life expectancy and quality of life for CF subjects.
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Lung function decline relates to mortality [2] and most
patients die from respiratory insufficiency. Therefore, research
aimed at preventing lung function decline should receive
highest priority.
1.2. Challenges for CF trials
In the last decades, the number of clinical trials in the
field of CF has increased [3]. In the period 1961–2002, eight
hundred and five trials were identified, but 63% of these were
performed in the last 5 years. This increase in number was
not paralleled by an increase in the number of multicentre
large size trials. Therefore, many if not most clinical trials
conducted in CF patients have not conclusively answered
the research question posed. The clinical phases of CF
drug development face challenges related to the disease, the
organization of care in CF centres, the CF patient population
and regulatory authorities [4].
CF is a complex genetic disease of a progressive nature.
The wide variation in causal mutations is in part responsible
for the type and severity of the disease process [5]. But
even in subjects with the same mu tation, the severity of
organ involvement varies [6]. Between subject differences
considerably influence the outcome of drug testing.
CF study design needs to take into account evolving
aspects of the disease process. At present about 50% of
patients with CF are children. With the advent of newborn
screening the need for clinical research in this young age
group is highlighted since many aspects of standard CF care
in the young are not evidence based [7]. Even with the current
best standards of care and despite good nutritional status
and preserved lung function, 50–80% of children with CF
identified through newborn screening develop bronchiectasis
by the age of 5 years [8,9].
Centralized care in appropriately staffed dedicated CF
centres leads to improved outcomes [10,11]. However, not
all CF care centres have the appropriate staff, expertise
and structure to conduct clinical trials [12]. Even if the
infrastructure is excellent, there are a limited number of CF
patients in individual CF care centres. Hundreds of patients
are needed to assess drug efficacy in phase III studies. There
are competing clinical trials and the availability of patients is
further reduced by limitations related to age and disease status
in specific study protocols.
Even if pr emature mo rtality is a reality, this is often
not consciously considered by individual CF patients and
their parents. Improved outcomes, especially maintained lung
function in young CF children, have changed the face of
the disease. Most children with CF live active “relatively
normal” lives despite the burden of treatment. The current
course of the disease with typical lung function decline in
later adolescence and young adulthood is a reality better
appreciated by experienced CF clinicians than by CF patients
and their parents. Regretfully, subject participation in CF
clinical trials is only 5–10%. Reasons for CF patients
declining to participate in trials include lack of time and fear
of side effects. The need for CF research should be explained
when parents are informed of their child’s diagnosis. In
addition, physicians should find a better balance between the
dual message of cu rrent better outcome, but the still nearly
uniformly life shortening nature of CF.
Research in children is more complex from an ethical
and regulatory perspective. To determine treatment efficacy,
disease stag e is likely to be as important as subject age. Still
pharmacokinetics of drugs must be eva luated separately in
Regulations such as the EU Directive on clinical trials
ensure high standards and patient safety. But, increasing
bureaucratic demands pose a barrier for orphan disease
research where the financial profit of drug development is
limited. Assigning orphan drug status [13] and specific task
forces to boost progress in the treatment of orphan diseases
are therefore of paramount importance. As an example,
the seventh framework program (FP7) of the European
Commission will support projects for “clinical development
of substances with clear potential as orphan drugs”.
Due to the challenges enumerated, the most appropriate
action in CF research is to form larger operational groups
and to focus on both study quality and quantity. Multicen tre
trials improve statistical power, enhance external validity and
through rapid recruitment, give more timely results. On the
other hand, additional coordination is needed to cope with
practical difficulties such as logistics, costs and in ter-centre
communication and standardization of procedures.
1.3. History of clinical trial networks
The first clinical trial networks were developed in the field
of cancer research, for example the Cancer and Leukemia
Group B (“CALGB” 1956 US) or the European Orga-
nization for Research and Treatment of Cancer (“EORTC”
(initially named “GECA”) 1962 EU).
The “Greenberg Report” written in 1967 and published in
1988 describes the organization, review and administration of
cooperative studies as well as the basic components required
for a research network [14]. It explains the crucial role of the
coordinating centre to continually maintain communication
between all participants. It also highlights the importance
of critically reviewing candidate studies to judge scientific
quality, feasibility, design and potential benefits.
Since the 1960’s, several disease specific clinical trial
networks have been developed, which have successfully
developed new treatments for specific patient groups (e.g. The
Asthma Clinical Research Network (“ACRN” 1993) or the
Acute Respiratory Distress Syndrome Network (“ARDSnet”
1994). Examples specific to Europe are the Pediatric European
Network for Treatment of AIDS (“PENTA 1991) and the
European Myeloma Network (“EMN” 2003).
The old fashion point of view that research in children
is unethical has led to the off label use of many drugs
in children. In Europe as well as in the USA there is in-
creasing awareness that research in the paediatric age g roup
should be promoted. In Europe this is the role of the
Paediatric Committee (PDCO) of the European Medicines
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K. De Boec k et al. / Journal of Cystic Fibrosis Volume 10 Suppl 2 (2011) S67S74 S69
Agency (EMA). As a result, several paediatric networks have
been established (e.g. the European Society for Paediatric
Nephrology (ESPN) and the Paediatric Rheumatology Eu-
ropean Society (PRES)). Other welcome initiatives are the
obligation to have a Pediatric Investigation Plan (PIP) for
every new investigational d rug application and the creation
of an association of paediatric networks. For additional in-
formation, we refer the Reader to
htms/human/paediatrics/regulation.htm and http ://www.ema.
1.4. Goals, advantages and disadvantages of clinical trial
For diseases with relatively small patient populations
such as CF, clinical trial networks provide a centralized
resource and adequate access to patient populations for the
successful execution of clinical trials [15]. In this way,
adequately p owered clinical trials can be conducted and
drug development for orphan diseases is facilitated. Also the
quality of medical science at participatin g sites is enhanced
by the combined expertise of multiple participants and the
training opportunities that are offered. A significant reduction
in the enrollment period can b e obtained as a result of the
larger patient pool.
By using standard operating procedures to measure out-
come parameters and increasing the expertise of personnel
at CF centre, variability in results will decrease. As a result,
fewer patients will be required to demonstrate clearly a signif-
icant effect of the investigational product [16–18]. Improved
knowledge about the natural course of the disease through
analyses of data in patient registries will help to define the
most important research questions leading to more evidence
based study design and sample size calculation [18].
Possible disadvantages are the cost, the more complex
decision-making process and the inadequate recognition of
individual investigators in multicentre research [15].
1.5. CF specific networks in the US and Europe
Established in 1998, the US Cystic Fibrosis Foundation-
Therapeutics Development Network (CFF-TDN) has proved
highly effective at accelerating clinical trials of new therapies
for CF. Uniting CF patient parent organizations and academia
establishes powerful alliances for CF patien t care and therapy
development. Patient parent organizations provide finances,
academia provide scientific expertise and both provide expert
leadership. Although countless excellent people h ave b een
involved in the success of the CFF-TDN, the visionary
leadership of Robert Beall and Bonnie Ramsey is recognized
by all. The CFF-TDN started its activities with 8 centres
selected by competitive application . The network expanded
to 18 sites in 2004 and more recently to 77 centres.
This expansion is necessary since more than 30 different
therapies are currently under development (see http://www. Together, the 77
centres provide a pool of 19,000 CF patients for clinical trials.
The centres are supported by a central coordinating centre at
Seattle Children’s Research Institute and 7 reference centres
each specializing in the standardization and interpretation of a
major CF outcome measure. The success of the CFF-TDN in
the US has been remarkable. For this reason, the NIH plans to
exploit the CFF-TDN organization and develop a therapeutic
pipeline similar to that of CFF as a g eneric model to improve
research efficacy for rare diseases [19].
Initiatives to organize CF clinical research have been
underway in Europe for some time. Examples include the
Scandinavian CF Study Consortium, the German CF re-
search organization (
1835.0.html?&L=0) and the UK CF gene therapy consortium
( But many studies surpass
the capacity of national patient groups. Hence, the need for
a pan-European initiative. The ECFS-CTN is the European
answer to the CFF-TDN. Many research ideas have been
pioneered by European researchers including application o f
antibiotics via inhalation to treat CF lung disease, defining an
eradication strategy for early Pseudomonas aeruginosa lung
infection, highlighting the parallels between diffuse panbron-
chiolitis in Japan and CF lung disease which led to the use
of macrolides to treat CF lung disease, developing ursodeoxy-
cholic acid treatment for CF liver disease and recognising
the importance of polyunsaturated fatty acids (PUFA) in CF
pathophysiology [20–26]. But in Europe national borders have
often hindered the formation of larger operational networks to
definitely settle research questions
1.6. Conclusion
The rationale for setting up the ECFS-CTN is to optimize
the development and evaluation of new and approved treat-
ments for CF in pan-European clinical studies. This includes
advising on optimal study design, identifying the most appro-
priate target population, improving sample size calculations
by using real life data and decreasing sample size by stan-
dardizing outcome parameters. Besides study design, other
important roles of the ECFS-CTN are to motivate patients to
take part in research and promote the safety of participants in
clinical trials. The example of the CFF-TDN is inspiring and
proves this can be achieved
2. Network function
2.1. Establishment of the ECFS-CTN
ECFS presidents Gerd Döring and Marie Johannesson took
preparatory steps to form a European clinical trial network [4].
The ECFS leadership of Professor Stuart Elborn continued in
the same spirit but the EuroCareCF program was the catalyst
for this project, leading to the creation of the ECFS-CTN,
which commenced its activities in January 2009.
A structured process had taken place to ensure a just and
solid basis for the ECFS-CTN. A feasibility questionnaire
was sent to all European CF physicians known to the ECFS.
This questionnaire asked CF centre directors whether they
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were interested in participatin g in a European clinical trials
network as well as to report the number of CF patients
under their care. Of 139 replies, 127 were positive and 95
centres responsible for the care of more than 100 CF patients
were identified. A second in depth questionnaire was sent
to the directors of these 95 centres. Centres were asked to
report patient potential according to age-classes, verify that
they complied with the ECFS consensus for standards of
patient care, report the experience of site-director and staff
in clinical trials, provide proof o f Good Clinical Practice
(GCP) accreditation of principal investigator and staff, report
the centre’s track record in performance of clinical trials,
availability of study personnel and specific measurement
techniques, presence of an interactive database to quickly
check inclusion and exclusion criteria for clinical trials and
provide proof of institutional support for participation in the
ECFS-CTN. Preference for sites with both paediatric and
adult CF patients was specified. Neighbouring CF centers
were allowed to group themselves into one operational
unit provided one principal investigator would oversee the
operation of the group and communication within and outside
the group. Stuart Elborn and a cancer research specialist then
ranked the applications. Figure 1 shows the 18 centres from
8 d ifferent countries selected to form the first wave o f the
ECFS-CTN. There is no hierarchy between centres; all are
equal partners in the ECFS-CTN.
2.2. Aims
The aim of the ECFS-CTN is to improve the quality and
quantity of clinical research in the area of CF and to bring new
medicines to patients faster This is achieved by establishing
a network of clinical trial sites according to uniform state-of-
the-art quality criteria, by setting-up an appropriate structure
Fig. 1. ECFS-Clinical Trials Network site locations: 18 sites in 8 countries.
supporting the network in the acquisition, planning and
conduct of clinical trials and finally by attracting projects in
cooperation with non-profit organisations, academic centres
and pharmaceutical or medical-device companies.
2.2.1. Overall function and agreements between ECFS-CTN
members (“Code of conduct”)
Only studies that are evaluated by the protocol review
committee are potential studies to be conducted through the
network. All ECFS-CTN p artners refer requests by pharma-
ceutical companies or clinical research organisations (CROs)
for participatio n in CF studies to the ECFS-CTN coordinating
centre. The code of conduct also provides directions on con-
fidentiality, conflict of interest, publication policy, financial
agreements and communication. The sites agree to comply
with the European clinical trials d irective (GCP-compliance)
and to meet and maintain the requirements for membership
in terms of patient numbers, staff structure, capabilities, com-
petencies, accreditations, continuous education and processes
required by the ECFS-CTN. Other responsibilities of member-
ship are recruitment of patients according to agreed timelines
and number, timely pr otocol review and replies to feasibility
requests, commitment to share clin ical trial expertise with
other centres within their region and swift communication
with the coor dinating centre.
2.2.2. Building a positive p artnership with patient parent
When the ECFS-CTN was established, it was realized
that the active involvement of patient organizations is critical
to the network’s success. Therefore one member of the
ECFS-CTN’s Executive Committee represents patient parent
organizations. Patients need to be informed about why clinical
research is important. They also need the right information to
promote better participation in clinical trials. To keep patient
parent organizations fully informed about the activities of the
ECFS-CTN, a newsletter is distributed regu larly. Hope fully
these actions will boost p atient participation in c linical trials.
2.2.3. Building a positive partnership with pharmaceutical
The ECFS-CTN seeks to interact with pharmaceutical
companies at an early stage in the design and development of
clinical trials, at a time when it can actively influence protoco l
design. The protocol rev iew committee provides feedback
on a proposed protocol and suggests changes in the general
protocol design, the choice and the frequency of assessing
endpoints as well as inclusion and exclusion criteria. At the
request of pharmaceutical companies, CF centres can assess
feasibility by consulting their databases to determine how
many of their subjects meet certain inclusion and exclusion
criteria. In addition th e protocol review committee will give
a priority score to a trial. Because so many competing
trials need to be performed, this is of great relevance.
By interacting early with pharmaceutical companies and by
providing advice about protocol design, patient recruitment
is improved. Also correct delineation of responsibilities and
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K. De Boec k et al. / Journal of Cystic Fibrosis Volume 10 Suppl 2 (2011) S67S74 S71
timing of interactions between pharmaceutical companies,
CROs and CF centres is needed.
2.3. Structure
During the first business meeting of the ECFS-CTN
which was held in Leuven in November 2008 and funded
by EuroCareCF, the basic structure of the ECFS-CTN was
established (Fig. 2). The ’code of conduct’ on how to share
information and the responsibilities of partners was agreed by
all partners.
2.3.1. Executive committee
The executive committee (EC) consists of 5 ECFS-CTN
principal investigators from 5 different countries and a rep-
resentative of patient parent organizations. During biweekly
teleconferences time is devoted to implement the policy that
was agreed during the business meeting. A delegate from
the ECFS and the ECFS-CTN Coordinator also participate in
these meetings. Meeting minutes are distributed to Primary
Investigators and Co-Investigators in all ECFS-CTN sites.
In any European Network, it is important to have enough
member states participate and to rotate principal responsibili-
ties through the different partners. For this reason, ECFS-CTN
Executive Committee members are appointed for 2 or 3 year
terms and are then replaced by other members to allow fresh
ideas to emerge and to make sure all partners have a feeling
of building, sharing and belonging.
2.3.2. ECFS-CTN coordinating centre
ECFS has committed itself to prime the network by
funding a clinical trial network coordinator and a part-time
secretary for 3 years. At the beginning of May 2009, the
network coordinator was recruited. The coordinator functions
as the daily contact person for the ECFS-CTN and interacts
with partners, industry, patient parent organizations and other
interested partners. The coordination centre also follows up
the decisions of the ECFS-CTN Executive Committee an d
Fig. 2. Current structure of the ECFS-Clinical Trials Network. For further information, see text.
other working groups, and coordinates the protocol review
process. A second part time coordinator has recently been
2.3.3. Steering committee
Twice a year, a face to face meeting is organized of the
executive committee, the network coordinator, a representa-
tive from each ECFS-CTN site, the leaders of the different
network committees, a representative of the ECFS, a represen-
tative of European patient parent organizations and an invitee
from the CFF-TDN.
During these meetings, an update is provided by all work-
ing groups, the financial plan is discussed, and action plans
for the next year are agreed. At the 2010 steering committee
meeting, the ECFS expressed its continued support for the
operation o f the ECFS-CTN and several European patient
organizations agreed to provide additional support for the
network. Furthermore the need for a second coordinator was
endorsed as were plans to modestly expand the ECFS-CTN.
2.3.4. Other committees
The Protocol Review Committee consists of a leader,
deputy and CF specialists with expertise in different domains.
The protocol review process is based on the one used by
the CFF-TDN with modifications to adapt to the European
experience. Prior to initiation o f proto col rev iew a contract
is set up between the pharmaceutical company and the
ECFS-CTN. For every proto col subm itted detailed feedback
about the study design is provided and a score is calculated
reflecting the priority and feasibility of the r esearch questio n
posed. Only protocols with the highest priority scores are
candidates for acceptance by the network.
The ECFS-CTN coordinator oversees the process and
timelines from first contact with a company, until delivery of
the final report and follow-up communication.
Diverse companies have been in close discussions with the
ECFS-CTN to have their protocols reviewed. By July 2010,
11 protocol reviews had been finalized. In response to requests
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S72 K. De Boec k et al. / Journal of Cystic Fibrosis Volume 10 Suppl 2 (2011) S67S74
for transatlantic clinical trials, a process for joint reviews with
the CFF-TDN has been set up.
The Standardization Committee is tasked to create high
quality standard operating procedures. It comprises several
sub-committees: Respiratory Function Explorations, Lung
Imaging (CT), Microbiological Explorations, Inflammatory
Markers, Nutritional Status Evaluation, Nasal Po tential Dif-
ference, Intestinal Current Measurements and Sweat Test.
Individuals outside the ECFS-CTN are invited to contribute
their expertise to these working groups.
The standardization subcommittees are preparing consen-
sus documents on outcome parameters. For this purpose, the
subcommittees will work in close contact with their counter-
parts in CFF-TDN reference centres. A concluding consensus
meeting to finalize the work was held in March 2010. The
main goals of the consensus documents will be to achieve
agreements on aspects of outcome parameters in clinical trials
(inside and outside the ECFS-CTN), to compose an inventory
of literature data and to agree on standard operatin g proce-
dures. It is hoped that the consensus documents will be of use
for authorities such as the EMA.
The Training Committee will build further research ex-
pertise. As a first step the possibility to follow online GCP
training has been provided to all sites and key people were
certified in early 2010 (financed by CFF). ECFS-CTN training
sessions for centre personnel covering different aspects of
clinical trial conduct, will also take place at ECFS meetings.
The first ECFS-CTN Training and Development meeting was
held at the 33rd European CF Conference, Valencia, Spain
(16–19 June 2010).
The independent Data Safety Monitoring Board (DSMB)
service is offered upon request. The cost for convening the
necessary expertise will be covered by individual pharmaceu-
tical companies or by the appropriate trial budget.
The aim of the Networking Committee is to interact
with existing organizations such as ECFS working parties,
National (generic) Networks, the EMA, the European Respi-
ratory Society, other scientific organizations etc. In this way
existing resources and available expertise is used, policies are
streamlined and impact is increased.
Teaming up with the ECFS Registry will be extremely
valuable and has already been anticipated. With the advent
of mutation specific CF trials, knowing the geographic
prevalence of individual mutations is crucial. In addition,
other relevant clinical data will become available from this
pan-European CF Patient Registry developed by EuroCareCF
and the ECFS, which will assist in realistic protocol design.
The registry data report from the year 2006 can be found
ECFRreportA2006.pdf, while the EuroCareCF report on the
demographics of CF in Europe has been published recently
2.3.5. Partnering with the CFF-TDN
As much as possible the ECFS-CTN aims to mirror
TDN structure and function. To ensure communication and
cooperation remains maximally efficient between the ECFS-
CTN and the CFF-TDN, monthly teleconferences have been
instituted. There are however major d ifferences b etween
the ECFS-CTN and the CFF-TDN. The CFF-TDN has an
established track record, the ECFS-CTN is emerging; the
sponsor of the CFF-TDN is the parent organization (the
CFF), the initial sponsor and initiator of the ECFS-CTN
is a scien tific society, the ECFS; the central organization
of the CFF-TDN has a large full-time staff, whereas th e
ECFS-CTN has recruited 1.5 coordinators and has a p art-time
2.3.6. Relationship with European non-ECFS-CTN centres
The ECFS-CTN’s standardization committee currently
welcomes input from experienced researchers outside the
network. This will further promote universal acceptance of
standard operating procedures. The ECFS-CTN aims to ex-
pand its network to include a larger number of centres by
2012. Input from non ECFS-CTN members is also necessary
in the data safety monitoring board. The ECFS-CTN seeks to
create an open spirit towards non-ECFS-CTN sites.
2.4. Communication
The coordinating centre is the central contact point for
receiving internal and external questions and for sending out
requests, meeting minutes, newsletters etc. The coordinating
centre is located in Leuven, Belgium and can be reached
by email ( or telephone (+32 479
The ECFS-CTN publishes and distributes regular newslet-
ters as well as a special newsletter for patients. General infor-
mation about the ECFS-CTN, information specific for com-
panies and newsletters are available from: http://www.ecfs.
eu/ctn. A password protected on line file repository for internal
use is available.
3. Evaluation of Clinical Trials Network
3.1. Short term
One of the priorities of the ECFS-CTN is to improve the
quality of CF clinical trials by standardizing methods (writing
Standard Operation Procedures) and by obtaining a reduction
in variability of outcome parameters (consensu s ou tco me
parameters). Also input from the protocol review committee
on draft protocols might impact on the schedule for patient
visits and procedures, leading to more patientfriendly study
design, greater patient satisfaction and increased patient
Research quantity can be expressed as for example the
percentage of patients enrolled and the percentage of target
Research efficiency can be calculated as for example the
time from regulatory packet receipt to first patient enrolled
and time from enrollment approval to first patient enrolled.
The quality delivered by the ECFS-CTN for one specific
study might also be measured by keeping track of the number
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K. De Boec k et al. / Journal of Cystic Fibrosis Volume 10 Suppl 2 (2011) S67S74 S73
of major protocol violations and by sending a questionnaire to
the sponsor that calculates a “quality score”.
3.2. Medium term
When sites are involved in multiple ECFS-CTN studies,
the parameters described above might be used to make a com-
bined analysis (e.g. yearly) that provides more information
about how sites are performing individually. This information
might also be used to tackle problems at specific sites and
if necessary to exclude sites from furth er participation in the
In the medium term, the operation of the ECFS-CTN as a
whole might be examined by analyzing the total number of
studies undertaken and the number of subjects coming from
ECFS-CTN sites participating in different clinical trials.
At this stage it will also be important to provide feedback
(study reports) to the scientific community and to CF patients
(via the website newsletters and conference presentations).
3.3. Long term
By analysing quantity, quality and efficiency as d escribed
above, the goal is to reduce the time required to bring new
effective medicines to the patient. This is of course whilst
maintaining optimal research quality and safety.
4. Other aspects
4.1. Funding
The ECFS has committed itself to further support the
network financially. The network activities will bring in some
money (e.g. fees for p rotocol reviews or feasibility checks),
but it is clear that these fees will never b e sufficient to sustain
We strongly believe that patients with CF and their parents
will play a crucial role in the success of the network, with
the result that effective new drugs are made available to all
patients as soon as possible. We therefore are thankful that
patient parent organizations in several participating countries
contribute to network costs (personnel and activities). Parent
organizations united by CF Europe agreed a memorandum
of understanding with the ECFS-CTN. This will likely be
the start of wider involvement of patient organizations in the
clinical trials network.
Efforts will be directed at accessing funds from the
European Union for network operation and for running CF
clinical trials especially with drugs licensed for indications
outside of CF treatment. Often drugs used in CF are not
profitable to pharmaceutical companies and thus unlikely
to be studied. In concert with other scientific organizations
the ECFS-CTN will list research priorities [28], work out
a scientifically sound and practically feasible protocol and
apply for EU funding.
4.2. Ethics
By grouping expertise and means in major European
centres research quality an d patient safety will be improved
thereby contributing to ethically sound research.
Of course all clinical research has to comply with European
as well as country specific laws and guidelines. Work
undertaken by the Ethical/Legal/Social Issues Workpackage
of the EuroCareCF project has produced a roadmap of all
governing European as well as country specific legislation
regulating paediatric clinical trials [29,30].
5. Conclusion
EurocareCF Workpackage 3, with its aim to investigate the
best strategy to design and conduct CF research facilitated the
formation of the ECFS-CTN.
At this moment, 18 centres in 8 countries are actively
involved in this network. The establishment of an execu-
tive committee, steering c ommittee, a coordinating center
and different subcommittees guarantee a solid organizational
structure with several links to different stakeholders.
The modalities for interaction between centres have been
described in a code of conduct to be adhered to by network
sites. Information about how the ECFS-CTN operates has
been provided to pharmaceutical companies.
Protocol review will improve the quality and feasibility
of clinical studies taken up by the network. Standardization
of outcome parameters will lead to uniform conduct and
improve quality performance in clinical trials undertaken by
the network.
A strong partnership with CF patient parent organizations
will increase awareness of th e need for efficient clinical
research to identify better ther apies faster and likely improve
patient participation in clinical research.
In conclusion, quite some work has already been un-
dertaken relating to the establishment and operation of the
ECFS-CTN. A firm foundation has been built to continue on
the multiple tasks that await attention in the years to come.
Christine Dubois from ECFS and the entire ECFS Board;
national CF patient and parent organizations and CF Europe;
ECFS-CTN Principal Investigators and Co-Investigators and
their site personnel; Bonnie Ramsey, George Retsch-Bogart
and Jill Van Dalfsen and their staff at the CFF-TDN; Robert J.
Beall, Preston W. Campbell, III, Bruce C. Marshall and their
staff at CFF; CF parents and patients. This work was sup-
ported by the European Union Sixth Framework Programme
(contract no. LSHM-CT-2005-018932, EuroCareCF).
Conflicts of interest
S. Conway is on the Advisory Board for Gilead, Novartis
and Vertex. K. De Boeck is or has been on the Advisory
Page 7
S74 K. De Boec k et al. / Journal of Cystic Fibrosis Volume 10 Suppl 2 (2011) S67S74
Board for Gilead, Novartis, Vertex and PTC and has done
consultancy for Eurand, Pharmaxis and Inspire.
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