Study type

Study topic

Medical device

Study type

Non-interventional study

Scope of the study

Healthcare resource utilisation
Validation of study variables (exposure outcome covariate)

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Name of medicine, other

FreeStyle Libre and LibreView (LV)

Medical condition to be studied

Diabetes mellitus
Population studied

Short description of the study population

Inclusion criteria
LV cohort: all adults from the LV system linked to the SNDS with a diagnosis of diabetes (T1DM or T2DM) and using FSL device for the first time since January 1st 2018.
TM cohort: all adults with diabetes identified in the SNDS database with a reimbursement for FSL, between 2018 and 2022. Within this cohort, individuals enrolled in the ETAPES program will be identified to compare: FSL users enrolled in ETAPES program versus FSL users not enrolled in ETAPES program.
Exclusion criteria
Individuals with discontinuous measurements of CGM will be excluded. The minimum number of consecutive days with CGM measurements that is required for each individual (for instance, 14 days every 90 days, as advised by the 2019 consensus) will be defined after discussion with the Scientific Committee and in view of the distribution of the CGM measurements over time.

Age groups

Adult and elderly population (≥18 years)
Adults (18 to < 65 years)
Adults (18 to < 46 years)
Adults (46 to < 65 years)
Elderly (≥ 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

70
Study design details

Study design

Two cohort studies of subjects with diabetes: one from the LV system with SNDS data linkage (LV cohort), and a 2nd in the SNDS (cohort TM) including those with diabetes with reimbursement for FSL (i.e., including subjects in and outside the LV cohort).

Main study objective

The research questions are (i) to assess the relevance of CGM-derived diabetes monitoring metrics for the prediction of micro and macrovascular complications, (ii) to assess the added value of the ETAPES program to LV system.
Objective 1 - allowing to answer the research question (i) - is to assess the prognostic value of CGM-derived diabetes monitoring metrics for determining the risk of microvascular and macrovascular complications.
Objective 2 - allowing to answer the research question (ii) - is to assess the clinical and economic benefits of the telemedicine program ETAPES for individuals using the LibreView diabetes telemonitoring platform with Freestyle Libre system.
LV system was part of telemedicine that facilitates monitoring individual’s metrics, thus the ETAPES (Expérimentations de Télémédecine pour l’Amélioration des Parcours En Santé) program defined in Article 54 of the Social Security Financing Act for the year 2018 (https://solidarites-sante.gouv.fr/soins-et- Maladies/prises-en-charge-specialisees/telesante-pour-l- access-for-all-to-remote-care/article/telemonitoring-steps?) has been set up by French authorities since June 2019 to experiment and assess the telemonitoring for individuals with diabetes. The experiments concern five pathologies including diabetes. The application for registration is performed by the attending physician or by the physician who carries out the telemonitoring. The program allows us to evaluate the coherence and relevance of telemonitoring projects and aims to support healthcare professional and better meet health care needs. The telemedicine has an important role in the management, by improving access to care, reinforcing preventive actions and avoiding hospitalizations.

Setting

To meet the objective 1, a cohort study of individuals with diabetes from the LV system with SNDS data linkage (LV cohort) will be carried out. It will include all individuals using FSL for the first time between 2018 and 2022 with a first date of glucose measure identified in LV system since 01/01/2018 (i.e., index date). Individuals of the cohort will have a 5-year history period before index date, and 1 to 6 years of follow-up in the SNDS. To cover the overall study period, LV data will be extracted from January 1st 2018 to December 31st 2022 in two steps: the first will be in 2024 and the second in 2025.
To meet the objective 2, a cohort study of individuals with diabetes with a reimbursement for FSL - including individuals who could not have been linked to SNDS and thus who are not present in the LV cohort -, between 2018 and 2022, will be carried out in the SNDS (cohort TM). Individuals of the cohort will have a 5-year history period before the provision date of the telemonitoring device and from 1 to 6 years of follow-up. Within this cohort, individuals enrolled in the ETAPES Program will be identified to compare FSL users enrolled in ETAPES program versus FSL users not enrolled in ETAPES program.

Comparators

In the LV cohort, there is no comparative group.
In the TM cohort, the exposure will be the use of FSL (LPP codes: 1190296, 1102257, 1110720, 1103570) and the enrolment in ETAPES program allowing to define the following comparative groups: FSL users included in ETAPES vs. FSL users not included in ETAPES.

Outcomes

Primary outcome: In both LV and TM cohorts, the first occurrence of a microvascular complication (diabetic neuropathy, retinopathy or nephropathy) or a macrovascular complication [heart failure, MI, stroke, Peripheral artery disease (PAD)], considered as a composite outcome or separately.
Secondary outcomes:
In both LV and TM cohorts: all-cause mortality, hospital admission for any cause
In the TM cohort only: other healthcare resources use (medical visit, emergency visit, etc.), costs (from a payer perspective).

Data analysis plan

LV cohort:
−Description of baseline characteristics, the values and changes in CGM metrics during the follow-up period for individuals in the LV cohort, both overall and stratified according to absence/presence of any micro-macrovascular complications before the index date;
−Estimation of crude incidence rates for all outcomes, as well as cumulative incidence, using 1-Kaplan-Meier estimator (for death) and cumulative incidence function (CIF) for non-fatal outcomes, considering death as competing risk;
−Assessment of the prognostic value of each CGM metric for the different outcomes using DRS-adjusted Cox model in both LV sub-cohorts, with and without prior micro-macrovascular complications. In these models, the independent variables include DRS (in deciles), CGM metrics calculated within the initial 90-day time window, and exposure to cardiovascular drugs during the follow-up period as time-varying covariates. Sensitivity analyses will also be conducted using alternative time windows (14 days, 1 month, 6 months and 12 months) for CGM metrics calculation.
−Comparison of the prognostic value of different CGM metrics using measures such as concordance index (c-index), time-dependent AUC, integrated Brier score…;
−Assessment of the association between each CGM metric and the primary outcomes using a “nested case-control design”;

TM cohort:
−Description of baseline characteristics of the TM cohort overall and according to enrollment in the ETAPES program or not (FSL users with ETAPES versus FSL users without ETAPES);
−Comparison of the risk of clinical outcomes between TM sub-cohorts using IPTW-adjusted Cox model for death and IPTW-adjusted Fine and Gray model for non-fatal outcomes.
−Comparison of reimbursed costs between TM sub-cohorts using an IPTW-adjusted multivariable linear regression model and of the healthcare resource utilization during the follow-up period using standardized differences.