InFocus France Epidemiological Study of Health Burden in Major Hypertriglyceridemia

cross-sectional study involving a sample of FCS and MCS patients in 1:1 ratio. The study was run in seven academic reference centers in France. Adult patients with documented history of fasting TG > 10 mmol/L (885 mg/dL) were recruited. Patients had to be genetically characterized or MCS patients had a MCS score ≤ 9 [11]. Group sample sizes of 19 FCS and 19 MCS have been calculated to achieve an at least 80% power to detect a 40% difference in the frequency of abdominal pain assuming that 90% of FCS patients would complain about abdominal pain.

The study protocol was approved by a nationally appointed ethics committee (Comité de Protection des Personnes - Ile de France 5) under number 18040. The study protocol complied with the ethical guidelines of the Declaration of Helsinki and the French Bioethics Law Jarde. The data management complied with the CNIL requirement. Each patient was informed about the aims and constraints of the study and signed a non-opposition form prior to any study procedure.

Health Burden assessment The French IN-FOCUS study was designed to capture current and retrospective data in FCS or MCS. Patients were called by the participating centers and were proposed to answer a paper questionnaire or to connect to a web-based questionnaire The questionnaire was divided into sections specifically assessing various domains of their experience: demographic data, signs, symptoms and complications of the disease, healthcare circuit, management, relationship with healthcare providers, and burden of the disease on daily life. (Details are available as supplementary material S1). The questionnaire focused on symptoms because the interest of quality of life assessment tools is debated in rare diseases with episodic manifestations. Indeed, most of these tools refer to a limited recall period.

Data analysis The statistical analysis was performed by Soladis (Lyon, France) using the Statistical Analysis System (SAS) software 9.4 (SAS Institute, Cary, NC, USA). Continuous variables were summarized by the number of observed data, mean, standard deviation (SD), median, first and third quartiles. Categorical variables were described as numbers and percentages calculated on the number of observed data. FCS and MCS subjects were compared using Student's t test or U Mann-Whitney's test. Categorical variables were compared by the chi squared test or the Fisher's exact test. Tests were two-sided and the significance threshold was set at 5%. No adjustment of the Type 1 error risk was made for multiplicity. Impact of history of AP was evaluated in a multivariable model (logistic regression for binary variables, ordinal logistic regression for ordinal variables) including the type of disease (FCS or MCS), history of AP and the interaction between these two predictors.