The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Abstract

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients.

FIGURE 1

Map showing the participating centres of the clinical trial network for primary ciliary dyskinesia (PCD-CTN) (red dots). The PCD-CTN consists of 22 trial sites from 12 European countries including >3000 children and adults with PCD. The map was created with R [16] and RStudio [17], the packages “maps” [18], “ggplot2” [19] and “dplyr” [20] were used.

FIGURE 2

Organisational diagram representing the structure of the clinical trial network for primary ciliary dyskinesia (PCD-CTN). The PCD-CTN was founded under the framework of the European Respiratory Network (ERN)-LUNG PCD Core in 2020. Core structures are the steering committee (SC), the executive committee (EC) and the coordinating centre. The coordinating centre provides a director and an academic secretary. The EC includes the PCD-CTN director and both deputies, the ERN-LUNG PCD Core coordinator and one additional ERN-LUNG PCD Core member representing three different European trial sites. The SC is composed of one principal investigator from each PCD-CTN member site, all members of the EC, the chair of the additional committees, and all appointed patient–parent representatives. The PCD-CTN includes several subcommittees: a committee in charge of data safety monitoring and committees for protocol review, training and standardisations of diagnostic procedures and important outcome measures. Important cornerstones of the PCD-CTN are a strong association with the ERN-LUNG International PCD Registry, the patient organisations and partnering networks, like the PCD Foundation in the USA.