Big data for a rare disease: complexity and usefulness

Introduction: Cystic Fibrosis (CF) is a genetic rare disease, but the concerted actions of medical personnel, researchers and patients allowed the institution of the European Cystic Fibrosis Society Patient Registry (ECFSPR) to collect information on a large number of patients from different European countries in a common format [1]. Objectives: The aim is to show the complexity of the ECFSPR that deals with the management and analysis of a large amount of data and the usefulness of such information for the care of CF patients. Methods: The ECFSPR collects information on CF European patients (diagnosis, genetics, lung function, growth, complications, microbiology, therapy and transplantation) collated annually by national CF registries and individual CF centres since 2003 (cross-sectional data till 2007, longitudinal data from 2008): it includes data of about 30,000 patients from 22 countries [2]. In order to identify and solve problems, a team that daily works on the ECFSPR was set up ‘service desk’ together with an executive committee and a steering group composed by national representatives that define the major activities of the ECFSPR (data protection legislation, use of data). The research activity is supervised by a scientific committee that identifies major research areas and approves the external data requests. Results: The critical aspects encountered in the institution of the ECFSPR (definition of the population under study, of inclusion criteria, of what to measure and how) were dealt with a definition group whose members have different expertise and a long experience in CF in creation of healthcare databases. Assessment of whether patients registered meet the inclusion criteria, data quality controls and data management, handling of missing data, maintaining patient confidentiality and dissemination of data are activities that need to be carried out daily. The assessment of the compliance of the inclusion criteria is responsibility of the national CF registries and individual CF centres since the information sent to ECFSPR are not enough to decide if patients can be included or not. The experience and the expertise of each member of the data quality control group allowed creation of a complete and shared list of data quality controls that are performed by all national registry data managers before sending the data to the ECFSPR. The data management and the handling of missing data are the main activities of the working group: from the uploading of the data to the freezing of the database through the process of correction of the inconsistencies found in the data, the registry coordinator, the service desk and the statistician work in close contact with the national and centres representatives. Maintaining patients confidentiality is one of the crucial aspects in order to reassure patients that decide to give the consent of the use of their data. With a clear language, the ECFSPR gives the necessary information to the patient in order to ensure that security measures meet data protection legislation and are updated if necessary. The availability of the information on a large number of patients affected by a rare disease allows the study of the epidemiology of the CF [3, 4], also focusing on CF atypical patients. The availability of this information allows also the identification of group of patients eligible for clinical trials that, otherwise, could not be carried out if only a small number of patients were involved. Pharmacovigilance is a potential aspect that can be investigated in order to record adverse events following the use of treatments. Monitoring care services in the European countries and, for future, planning adequate CF centres are other activities that the availability of a large amount of information makes possible [5]. Giving an answer to a clinical request needs to take into account that these are registry data and they are not collected with ad hoc studies. However, studies on registry data can have an explorative nature and ad hoc studies can be carried out starting from the first results obtained by the ECFSPR. Conclusions: The complexity of the ECFSPR is magnified by the international setting: agreement on all the aspects of the involvement into the ECFSPR is not easily reached in a short time. However the usefulness of information for the care of CF patients that can be obtained from a European registry for a rare disease is inestimable, therefore all the difficulties are faced and overcome. References [1] Viviani L, Zolin A, Mehta A, Olesen HV. The European Cystic Fibrosis Society Patient Registry: valuable lessons learned on how to sustain a disease registry. Orphanet J Rare Dis. 2014 Jun 7;9(1):81. doi:10.1186/1750-1172-9-81. [2] Zolin A, McKone EF, van Rens J et al. ECFSPR Annual Report 2010, 2014, accessed on 15th May 2015. [3] Kerem E, Viviani L, Zolin A, MacNeill S, Hatziagorou E, Ellemunter H, Drevinek P, Gulmans V, Krivec U, Olesen H on behalf of the ECFS Patient Registry Steering Group. Modifiers of pulmonary function in cystic fibrosis: analysis of the data of the ECFS Patient Registry. Eur Respir J. 2014 Jan;43(1):125-33. doi: 10.1183/09031936.00166412. [4] De Boeck K, Zolin A, Cuppens H, Olesen HV, Viviani L. The relative frequency of CFTR mutation classes in European patients with cystic fibrosis. J Cyst Fibros. 2014 Jul;13(4):403-9. doi: 10.1016/j.jcf.2013.12.003. [5] Burgel PR, Bellis G, Olesen HV, Viviani L, Zolin A, Blasi F, Elborn JS; ERS/ECFS Task Force on The Provision of Care for Adults with Cystic Fibrosis in Europe. Future trends in cystic fibrosis demography in 34 European countries. Eur Respir J. 2015 Mar 18. pii: ERJ-01963-2014.