Workpackage 2: Clinical Coördination




To establish a European-wide network of standardized population-based registries representing a population of about 41 million people


To implement a simple, standardized and flexible European-wide database linking clinical data and biological samples for the -omics analyses in pillar II and integrative analysis in pillar III


To generate a final guideline concerning the minimal requirements for collection and storage of clinical and epidemiological data throughout Europe


To generate a final guideline concerning the collection and storage of biological materials considered in the workpackages of pillar II


To generate two population-based case-control cohorts to provide the basis for the work in pillar II


To ensure an adequate coordination concerning the distribution of biological materials that serve as input for pillar II


The main objective of the clinical coordination effort is to generate patient cohorts for discovery, replication and validation.

Task 1. Coordination of recruitment of prospective population based discovery and replication cohorts (partners 1, 10). For the discovery and replication cohorts (crucial cohorts for this application as all –omics will be applied) we chose to select well-established population-based registries of Euro-MOTOR partners that are also involved in EURALS: Piemonte/Valle d’Aosta, Italy (4.5 million, Chio/Beghi); Puglia, Italy (4.5 million, Chio/Beghi); Lombardia, Italy (5 million Chio/Beghi); Ireland (4.5 million, Hardiman) and The Netherlands (16 million, Van den Berg). These registries represent a population of 34.5 million in total allowing us to have access to approximately 690 patients/year. Previous experience by EURALS members shows that response rates in epidemiologic ALS research are generally high (~80%), for both patients and controls. Nevertheless, power calculations in the current proposal will be based on a conservative rate of 65%.


Task 2. Drafting a guideline on collection and storage of clinical data and biological samples (partners 1, 10). A meeting will be organized with the members of the Euro-MOTOR consortium in order to generate a final guideline concerning the minimally required clinical data that are being collected and stored throughout Europe. The European and national regulatory requirements of each country related to the share of clinical data will be followed and incorporated in the guideline. The guideline will also include rules for access to de-identified data by the members of the consortium, for the protection of Human Subjects and Privacy Issues, and for publication and intellectual property. Access to original data will be permitted only when a brief description of their proposed use is given and when the terms and conditions for use are satisfied.  The Euro-MOTOR Executive Committee will review a request for immediate approval or for further review. Similarly a guideline for storage and exchange of biological materials will be established: this guideline will pay particular attention to the European and national regulatory requirements and will include rules for the utilization of the stored material by the members of the consortium. The access to biological material will be subject to the same rules identified for clinical data.


Task 3. Expand prospective cohorts to 1600 patients and 3200 controls for environmental/lifestyle data (partners 1, 10). The discovery and replication cohorts are crucial for the integrated analyses of all –omics data and environmental/lifestyle datasets. These cohorts consist of 400 patients and 400 controls each: for each individual a complete set of clinical data, environmental/lifestyle data as well as blood samples (DNA, RNA, plasma) needs to be acquired. Only for the exposome WP we will continue to collect clinical and environmental/lifestyle data in a population-based fashion through questionnaires/telephone interviews to arrive at a cohort of 1600 patients, and 3200 controls after three years of collection.

The population-based character will be guaranteed by the active attempt for complete ascertainment of all patients with ALS: several well defined sources are periodically interrogated by each of the national registries including records from several physicians (neurologists, neurophysiologists, and pneumologists), riluzole pharmacy records, lay association archives, general practitioners’ records, and administrative sources (hospital discharge records, disability lists, etc.). Ensuring that the cohorts are properly frequency matched on gender and age, the capture-recapture methodology is executed well with adequate, independent sources.  

For each registered case, two normal individuals will be selected from the lists of the general practitioners living in the case’s geographic area. The identification of two controls for each case helps in enforcing the matching procedure and in reducing the size of the ALS population to be studied. Matching will be for gender and age (+/- 2.5 years). As indicated by previous experience, the use of the general practitioners’ lists is a valuable, accessible and economic source of representative controls.

Task 4. The coordination of including retrospective samples for validation purposes (partners 1, 10). The validation cohort consists of patients’ samples retrospectively collected by Euro-MOTOR partners (partners 2,3,5,8,9,10,12, and 14, see table 2 for numbers) and samples from new patients and controls. The advantage of the validation cohort is the huge increase in power compared to the prospective cohorts, especially with regard to DNA samples.

The collection of biological specimens for the study of genetic and biochemical risk factors will be performed in line with the legal requirements of each participating country. For each registered patient (and matched control) blood will be taken after written informed consent for the collection of the material required to comply with the study protocol.

The challenge will be to have standardized clinical and biological data derived from these cohorts across Europe, and to effectively share these within Euro-MOTOR.  

The database will be structured in order to facilitate queries to identify specific subset of patients and identify the locations where biological samples are stored (virtual biobank). Interested laboratories may use the database in order to request samples from several European locations. The database will promote contact between the -omics laboratories and the single institutions where biological samples are stored. It will coordinate the sending of samples to laboratories. Periodical updating of the clinical data and biological samples collected by the different centres will be performed through a newsletter to all the members of the network in order to promote the use of  stored samples.