Constances is a large-scale French epidemiological study, funded by the Investissements for the Future program (PIA) and supported by CNAM and CNAV, respectively National Health Insurance and Retirement Funds. It targets adults affiliated to the French Social Security system (over 85% of the French population). Recognized as a National Biology and Health Infrastructure, it offers access to researchers and public health organizations. This "generalist" cohort aims to cover a wide range of health problems and their determinants, without limiting itself to a specific research question, thus facilitating the analysis of a multitude of scientific problems in the health field.
The Constances cohort is based on a representative sample of the French population aged 18-69 (born between 1941 and 2000) at the time of the invitation, and affiliated to the General Social Security Scheme.
- Selection of eligible subjects:
Carried out by random drawing from a database of all people living in France managed by the CNAV. The random draw was stratified with unequal probabilities according to age, gender and SES, over-representing categories that usually do not participate much in surveys. Eligible subjects were selected from residents of the “departments” where the 21 Social Security Health Examination Centers (CES) involved in the study are located. Distributed throughout mainland France to ensure good coverage of the main regions, these CES provide the necessary infrastructure for inclusion and follow-up medical examinations.
- Invitation to participate:
Selected subjects are invited by mail to participate in Constances, and to attend a CES for a health examination. An independent trusted third party manages the subjects' identifying information (names, addresses, etc.) and acts as a link between the participants and the cohort.
- Inclusion of volunteers:
People who accept the invitation fill in questionnaires at home and receive a comprehensive health examination at a CES, where they sign an informed consent form.
Recruitment of participants took place for the most part from 2012 to 2019, and ended in 2021, by which time the cohort numbered around 220,000 volunteers.
The Constances cohort includes a sample of subjects diverse in terms of age, gender and socio-professional category, with a slight majority of women (54%). The 220,000 participants enable the study of numerous health problems and risk factors. For example, by the end of 2023, the cohort had have recorded more than 25,000 cancer cases (including about 10,000 incidents since entry into the cohort). With an annual response rate of between 60% and 70%, and less than 0.5% of participants wishing to withdraw, the cohort benefits from strong volunteer support. The proportion of subjects lost to follow-up is extremely low, thanks in particular to linkage with national administrative databases where subjects continue to be monitored even if they no longer participate in active data collection.
The Constances cohort systematically collects a variety of data to monitor the health status, morbidity, mortality, risk factors and socio-demographic characteristics of its participants.
At baseline
Data are collected via questionnaires completed at home or administered by physicians in the CES:
- Socio-economic characteristics
- Lifestyle factors
- Personal and family medical history
- Data on health behaviors, occupational exposures
- Health conditions specific to women.
- Clinical and paraclinical examinations are carried out in the CES, including specific cognitive and functional tests for participants over 45.
- Residential addresses are geocoded since inclusion for all participants, and since birth for over 80,000.
During follow-up
Active follow-up with questionnaires: during follow-up, an annual questionnaire is proposed, in paper form or internet, depending on the volunteers' choice. A new health examination at the CES is proposed every 4 years.
Passive follow-up: CNAV provides Constances with information on people's socio-professional (employment or social benefit giving entitlement to retirement) and vital status, going back to the first job. The CNAM provides medico-administrative data in the SNDS since 2007. A biobank (blood and urine samples from around 60,000 participants) has been created.
Active follow-up with questionnaires: during follow-up, an annual questionnaire is proposed, in paper form or internet, depending on the volunteers' choice. A new health examination at the CES is proposed every 4 years.
Passive follow-up: CNAV provides Constances with information on people's socio-professional (employment or social benefit giving entitlement to retirement) and vital status, going back to the first job. The CNAM provides medico-administrative data in the SNDS since 2007. A biobank (blood and urine samples from around 60,000 participants) has been created.
Ongoing data enrichment
The CONSTANCES database is regularly enriched with a wide range of data drawn from a variety of databases. Socio-economic data concerning the residential context (deprivation index, access to healthcare, etc.) and the environment (pollution, pesticides, light, noise, etc.), thanks to geocoded residential calendars. Job histories linked to "jobs-exposure matrices" enable to reconstruct occupational exposure to various nuisances.
Quality control includes systematic analysis of non-response rates and cleaning of questionnaire data. Systematic quality control is also applied in the CES to assess the accuracy, reproducibility, concordance, internal and external validity of the data collected, and to study factors of variability. Epidemiological research assistants make regular site visits to check compliance with standard operating procedures. Data from national databases undergo specific validations to ensure the accuracy of certain medical diagnoses.
Biases linked to selection effects at entry in the cohort (volunteers may differ from non-participants according to health and social characteristics) are treated differently depending on the purpose of the analyses. For descriptive studies, sampling is designed to reflect the general French population. Stratified random selection and reweighting methods, including for non-participation and attrition, correct for potential bias. The reweighting uses data from a reference cohort, made up of around 435,000 people randomly selected from among all non-participants (refusal/non-return of response), passively monitored via the SNDS and CNAV databases. This representative cohort is used to calculate weighted prevalences of diseases and risk factors. During follow-up, administrative data from the SNDS and CNAV ensure that even non-active participants are tracked, enabling regular adjustments for attrition.