BMC Med

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates

Age impact on human papillomavirus vaccination in France in 2014: A study from the National Health Insurance Database

SummaryIntroductionHuman papillomavirus (HPV) is the main cause of cervical cancer. In France, since March 2007, HPV vaccination has been recommended for girls aged 14, in addition to a catch-up program for girls aged 15 to 23. In October 2012, the target population was changed to 11- to 14-year-old girls. The main objective of the present study was to evaluate the impact of the recommendation change on HPV vaccination coverage and compliance.MethodsWe conducted a descriptive study of the Échantillon Généraliste des Bénéficiaires (EGB), which is a random 1/97 permanent sample from the French National Health Insurance Database. We focused our analyses on girls aged 11 to 17 years who were covered by the main insurance scheme (which covers 77% of the French population).ResultsWe included 16,195 girls in this analysis. At the last update of the database (06/15/2014), 42% of 17-year-old girls had been vaccinated, with more than 50% of them having been vaccinated at age 14. Between January 2012 and June 2014, patients were reimbursed for a total of 7698 doses of the HPV vaccine. During the first trimester of 2013, the number of vaccinated 11- to 13-year-old girls increased, growing by more than 20-fold between the last trimester of 2012 (n=8) and the last trimester of 2013 (n=178). Less than 60% of the vaccinated patients received 3 injections.DiscussionImplementation of the new recommendations was rapid but had only a slight impact on vaccination coverage

Addressing the issue of bias in observational studies: Using instrumental variables and a quasi-randomization trial in an ESME research project

International audiencePurpose: Observational studies using routinely collected data are faced with a number of potential shortcomings that can bias their results. Many methods rely on controlling for measured and unmeasured confounders. In this work, we investigate the use of instrumental variables (IV) and quasi-trial analysis to control for unmeasured confounders in the context of a study based on the retrospective Epidemiological Strategy and Medical Economics (ESME) database, which compared overall survival (OS) with paclitaxel plus bevacizumab or paclitaxel alone as first-line treatment in patients with HER2-negative metastatic breast cancer (MBC).Patients and methods Causal interpretations and estimates can be made from observation data using IV and quasi-trial analysis. Quasi-trial analysis has the same conceptual basis as IV, however, instead of using IV in the analysis, a “superficial” or “pseudo” randomized trial is used in a Cox model. For instance, in a multicenter trial, instead of using the treatment variable, quasi-trial analysis can consider the treatment preference in each center, which can be informative, and then comparisons of results between centers or clinicians can be informative.Results In the original analysis, the OS adjusted for major factors was significantly longer with paclitaxel and bevacizumab than with paclitaxel alone. Using the center-treatment preference as an instrument yielded to concordant results. For the quasi-trial analysis, a Cox model was used, adjusted on all factors initially used. The results consolidate those obtained with a conventional multivariate Cox model. Conclusion: Unmeasured confounding is a major concern in observational studies, and IV or quasi-trial analysis can be helpful to complement analysis of studies of this nature

Addressing the issue of bias in observational studies: Using instrumental variables and a quasi-randomization trial in an ESME research project

Purpose Observational studies using routinely collected data are faced with a number of potential shortcomings that can bias their results. Many methods rely on controlling for measured and unmeasured confounders. In this work, we investigate the use of instrumental variables (IV) and quasi-trial analysis to control for unmeasured confounders in the context of a study based on the retrospective Epidemiological Strategy and Medical Economics (ESME) database, which compared overall survival (OS) with paclitaxel plus bevacizumab or paclitaxel alone as first-line treatment in patients with HER2-negative metastatic breast cancer (MBC). Patients and methods Causal interpretations and estimates can be made from observation data using IV and quasi-trial analysis. Quasi-trial analysis has the same conceptual basis as IV, however, instead of using IV in the analysis, a “superficial” or “pseudo” randomized trial is used in a Cox model. For instance, in a multicenter trial, instead of using the treatment variable, quasi-trial analysis can consider the treatment preference in each center, which can be informative, and then comparisons of results between centers or clinicians can be informative. Results In the original analysis, the OS adjusted for major factors was significantly longer with paclitaxel and bevacizumab than with paclitaxel alone. Using the center-treatment preference as an instrument yielded to concordant results. For the quasi-trial analysis, a Cox model was used, adjusted on all factors initially used. The results consolidate those obtained with a conventional multivariate Cox model. Conclusion Unmeasured confounding is a major concern in observational studies, and IV or quasi-trial analysis can be helpful to complement analysis of studies of this nature. </jats:sec

Distribution d'un horizon à forte cohésion au sein d'une couverture de sol aride du Nord-Cameroun : apport d'une prospection électrique (Distribution of hardpan in soil cover of arid zones. Data from a geoelectrical survey in northern Cameroon)

A study of arid-soil cover was carried out by resistivity survey and morphological observations. The main differentiation concerns a sandy hardpan that has a low resistivity. Its distribution is closely associated with differences in vegetation: it is (i) present and continuous at shallow depth (<1.5 m) in bare or herbaceous zones and (ii) deeper than 1.5 m or absent in arboreous zones. It is also suggested that the presence of hardpan is related to a clayey substratum, whereas its absence or deepening is related to a sandy substratu