The goal of the Constances project is to implement a large epidemiological cohort aimed at contributing to the development of epidemiological research and to provide public health information. The purpose of this cohort, created in the context of a partnership between the French national health insurance fund for employees (CNAMTS) and the French national retirement pension fund (Cnav), is to constitute an infrastructure open to the research community. Constances is labelled National Biology and Health Research Infrastructure by the French government's Commissariat-General for Investment..
Constances is a "general purpose" research infrastructure designed to help analysing a broad range of scientific problems. Constances was also designed as a public health and surveillance tool, thanks to the particularly exhaustive nature of the system for collecting and monitoring a great variety of data from a large representative sample of the adult population covered by the General Social Security scheme.
Subjects considered as eligible due to their age and place of residence are drawn randomly by stratified sampling with unequal probabilities, over-representing individuals with a higher probability of non-volunteering according to age, gender and SES. Random sampling is performed by the Cnav from the French national inter-scheme registry of health insurance beneficiaries (RNIAM), linked to the National careers management system (SNGC).
The Constances cohort constitutes a complex database with characteristics rendering it highly sensitive under the terms of the French data protection act, in particular due to the collection of personal data. Moreover, some data collected at the individual level come from linkage to national databases: National inter-scheme health insurance information system (SNIIRAM), causes of death information system (CépiDc-INSERM) and the Cnav (Annual Social Security declarations, Named quarterly data, absenteeism due to illness, Active solidarity income, maternity).
Very strict data collection, organisation, and management constraints are required. The procedures in place conform to legislative and regulatory texts intended to preserve high-level personal data confidentiality and security.
This invitation to participate to Constances implies to undergo a health examination in a health clinic. The randomly drawn individuals first receive at home an invitation letter presenting the project, along with a mail-back coupon enabling them to give their consent.
The persons having consented to participate in Constances are invited by letter to come to their health clinic, specifying the date and location of the examination. They also receive two self-questionnaires to be filled in at home: a health and lifestyle questionnaire, and a professional calendar tracing their full job history.
In addition to the self-questionnaire completed at home, subjects undergo a health examination used to collect health-related data: clinical examination, blood analysis, blood pressure, weight, height and waist-to-hip ratio, electrocardiogram and spirometry, sight and hearing examination. This examination is standardised by means of Standard Operating Procedures (SOPs) and permanent quality control is ensured in collaboration with the ClinSearch company and the Asqualab and Eurocell associations.
Additional questionnaires, to be completed on-site (whole-life occupational exposures, women’s health), are collected at the health clinic. The informed consent signature validates the collection of these data and authorises their use for research purposes.
Participants aged 45 years and over are invited to undergo a cognitive and functional check-up. This examination is performed by a neuropsychologist and includes a series of tests. The documents pertaining to this check-up (protocol, data collection form), along with related videos, are available on request.
A yearly postal or Web-based self-questionnaire is used for active follow-up at the subjects' homes, and an invitation to come to the health clinic once every 5 years is scheduled for all cohort volunteers.
Moreover, health and socio-professional data, along with causes of death, are regularly retrieved from the national health insurance, retirement pension fund and mortality databases.
The Constances cohort involves long-term longitudinal monitoring of volunteer participants. It cannot therefore be strictly anonymous as the various data concerning the individuals must be linked together throughout the follow-up and the data from different sources must be paired for each subject. Moreover, it must be possible to contact the participants (sending of questionnaires, newsletters, etc.) and to invite them to come in to their Health Clinic. It is thus essential to ensure that highly secure personal data collection and transfer procedures are followed to guarantee absolute confidentiality.
The underlying principle of these procedures is based on the assignment of multiple non-identifying numbers for each data stream, along with the implementation of independent transfer circuits between the various sources. A "trusted third party", accredited by the French national data protection commission (CNIL), acts as a conduit between the various streams and guarantees the confidentiality of all identifying data.
The data collection and management system architecture is based on processes intended to ensure that it is impossible for any person to gain (direct or indirect) access to identifiable data.
The system relies on file mapping each volunteer’s identity to a permanent anonymous number. This file contains no other information and is stored on an independent computer. It is drawn up and managed by an organisation acting as a "trusted third party", bound to medical and statistical secrecy and independent of the team managing the Constances project. The entire Constances system was authorised by the French national data protection commission (CNIL) and the INSERM Institutional Review Board.
CODE OF CONDUCT AND ETHICS
Ethical aspects associated with the participation of multiple partners are crucial to a project of this scope. Strict rules of ethics must be enforced with the cohort participants, along with the teams and various Constances partners. The main document defining the rules of ethics that apply to epidemiological activities is "Epidemiology ethics and best practices guidelines by the association of French-speaking epidemiologists" (Adelf).
Participation in the Constances cohort relies upon the freely consented volunteering of all participants who accept the invitation to participate. Upon enrolment, participants are given detailed information brochure, specifying the benefits of the project, but also its constraints in terms of data collection, management and use. Information feedback to participants is organised with a view to ensuring better adherence of the volunteers of the Constances cohort, throughout the follow-up period. This is also an ethical obligation with respect to participants and of code of conduct with respect to physicians and health clinic employees actively involved in the project.
The Constances cohort was granted the "Label of general interest and statistical quality" by the French national council for statistical information (CNIS).
A biobank, developed through the collection of biological samples in the health clinics, will be associated with the Constances cohort. An in-depth technical analysis was conducted for the creation of a large-scale collection, including several hundred thousand distinct samples, combined with a database of clinical, paraclinical, biological, behavioural and environmental information. The aim is to develop the largest possible collection of biological samples for the future (blood: serum, plasma, urine) and to enable the storage of more specialist samples for specific research purposes.
Investigating physicians validate certain identified health events (cancer, cardiovascular or neurodegenerative diseases, etc.). The purpose of these investigations is to collect data or documents (examination or hospitalisation reports, etc.) used to validate the health events and to collect detailed information essential for research.