Real-world expenditures and survival time after CAR-T treatment for large B-cell lymphoma in Switzerland: a retrospective study using insurance claims data

AIM OF THE STUDY: Newly approved therapies with high and uncertain budget impact pose challenges to public health care systems worldwide. One recent example is chimeric antigen receptor T cell (CAR-T) therapies for adults with large B-cell lymphoma (LBCL). This study’s primary objective is to examine the expenditures of Swiss public payers before, during, and after CAR-T cell therapy in patients with LBCL aged ≥30 years. Its secondary objective is to analyse 24-month survival rates. METHODS: This retrospective observational data analysis used the administrative databases of the Swiss health insurers Concordia, CSS, Groupe Mutuel, Helsana, ÖKK, Sanitas, SWICA, Sympany, and Visana. These health insurers or groups provide mandatory health insurance to approximately 78% of Swiss residents in 2021. Using the relevant procedure codes, we identified CAR-T therapies administered between October 2018 (first approval) and June 2021 (treatment identification cut-off). Patients aged <30 years were excluded because they might be treated for pediatric acute lymphoblastic leukaemia. Expenditures were categorised as pre-infusion, peri-infusion (excluding CAR-T therapy acquisition costs), and post-infusion based on the time of service provision. Overall survival rates were estimated using the Kaplan–Meier method. RESULTS: This study identified 81 patients aged ≥30 years, with a median follow-up period for censored observations of 27 months (interquartile range: 21–31 months). The median age group was 70–74, and 60% of patients were male. Mean healthcare expenditures per patient per month amounted to CHF 8,115–22,564 pre-infusion, CHF 38,490 peri-infusion, and CHF 5,068–11,342 post-infusion. For the total peri- and post-infusion period (i.e. 1-month before infusion to 23 months after infusion), mean healthcare expenditures amounted to CHF 215,737. The 24-month overall survival rate was 48% (95% confidence interval: 38–61%). CONCLUSIONS: Healthcare expenditures after CAR-T cell infusion are relatively high compared to previous estimates of patients with LBCL in the last year of treatment. Further research is needed to understand the drivers behind these post-infusion expenditures. Especially, clinical data should be used to assess the time until disease progression. The analysis of 24-month overall survival is consistent with results from the pivotal trials. Our findings stress the importance of post-approval studies to monitor real-world expenditures and outcomes related to innovative therapies

The FDR4ATMOS Project

The FDR4ATMOS project has two main tasks. The focus of task A is to update the SCIAMACHY processing chain for better Ozone total columns. After the full re-processing of the SCIAMACHY mission with processor versions 9 (Level 1) and version 7 (Level 2), the comparison with ground-based data showed that the total Ozone column showed a downward trend of nearly 2% from the beginning of the time series to its end. This trend is an artefact and is likely caused by changes made to the calibration algorithms in the Level 1 processor (the DOAS retrieval algorithm for Ozone was not changed). The most likely reason are changes in the degradation correction that lead to subtle changes in the spectral structures that in the retrieval are interpreted as an atmospheric signature. In task A we will update the Level 0-1 processor with the final aim of a mission re-processing. The second task in the FDR4ATMOS project is to develop a cross-instrument Level 1 product for GOME-1 and SCIAMACHY for the UV, VIS and NIR spectral range with a focus on the spectral windows used for O3, SO2, NO2 total column retrieval and the determination of cloud properties. Contrary to other projects, FDR4ATMOS does not aim to build a harmonised time series on Level 2 products but on Level 1 products, i.e. radiances and reflectances. The GOME-1 and SCIAMACHY instrument together span 17 years of spectrally highly resolved data. The goal of the FDR4ATMOS project is to generate harmonised data sets that allow the user to use it directly in long term trend analysis, independent of the instrument. Since this was never done for highly resolved spectrometers, new methods have to be developed that e.g. take into account the different observation geometries and observation times of the instrument without impacting the spectral structures that are used for the retrieval of the atmospheric species. The resulting algorithms and the processor should also be as generic as possible to be able to transfer the methodology easily to other instruments (e.g. GOME-2, Sentinel-5p) for a future extension of the time series. The FDR4ATMOS started in October 2019 and is currently in phase 1. We will present the goals of the project and first results

SCIAMACHY: Level 0-1 Processor V9 and Phase F Re-processing

SCIAMACHY (SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY) is a scanning nadir and limb spectrometer covering the wavelength range from 212 nm to 2386 nm in 8 channels. It is a joint project of Germany, the Netherlands and Belgium and was launched in February 2002 on the ENVISAT platform. After the platform failure in April 2012, SCIAMACHY is now in the postprocessing phase F. Its originally specified in-orbit lifetime was double the planned lifetime. SCIAMACHY was designed to measure column densities and vertical profiles of trace gas species in the mesosphere, in the stratosphere and in the troposphere (Bovensmann et al., 1999). It can detect a large amount of atmospheric gases (e.g. O3 , H2CO, CHOCHO, SO2 , BrO, OClO, NO2 , H2O, CO, CH4 , among others ) and can provide information about aerosols and clouds. The operational processing of SCIAMACHY is split into Level 0-1 processing (essentially providing calibrated radiances) and Level 1-2 processing providing geophysical products. The operational Level 0-1 processor has been completely re-coded and embedded in a newly developed framework that speeds up processing considerably. In the frame of the SCIAMACHY Quality Working Group activities, ESA is continuing the improvement of the archived data sets. Version 9 of the Level 0-1 processor includes - An updated degradation correction - Improvements to the polarisation correction algorithm - Improvements to the geolocation by a better pointing characterisation - Several improvements in the SWIR spectral range like a better dark correction, an improved dead & bad pixel characterisation and an improved spectral calibration The new format for the Level 1b and Level 1c will be netCDF V4. We will present the verification results and the results of the mission re-processing

SCIAMACHY V8 Solar Spectral Irradiance Validation

SCIAMACHY (Scanning Imaging Absorption Spectrometer for Atmospheric Chartography) on-board the ESA Envisat satellite platform provided daily solar spectra in the wavelength region from 0.24 μm to 2.4 μm. The instrument was operating for nearly a decade from August 2002 to April 2012. This document reports on the validation of the SCIAMACHY solar spectral irradiances (SSI) in its data version 8. Like other UV satellite sounders, the SCIAMACHY spectrometer suffers from optical degradation due to polymerisation of optical surfaces from the harsh UV radiation in space (e.g. Bramstedt et al., 2009; DeLand et al., 2012; Krijger et al., 2014). In data version 8 of SCIAMACHY a physical model of the scanner unit was implemented to provide a degradation correction (Bramstedt et al., 2009; Krijger et al., 2014). Comparisons with several other established solar reference spectra show agreement to within 4 % in most parts of the visible and near infrared from 350 to 1400 nm

The Uranus System Explorer (USE) – Unveiling the evolution and formation of icy giants

The results presented are the output of a student exercise carried out at the Alpbach Summer School 2012 , the topic of which pertained to the exploration of the giant planets and their systems. In this context, we propose in this paper the Uranus System Explorer (USE), a mission to investigate the Uranus planetary system and gain new insight into the formation and evolution of icy giants

SOLAR-ISS: A new reference spectrum based on SOLAR/SOLSPEC observations

International audienceContext. Since April 5, 2008 and up to February 15, 2017, the SOLar SPECtrometer (SOLSPEC) instrument of the SOLAR payload on board the International Space Station (ISS) has performed accurate measurements of solar spectral irradiance (SSI) from the middle ultraviolet to the infrared (165 to 3088 nm). These measurements are of primary importance for a better understanding of solar physics and the impact of solar variability on climate. In particular, a new reference solar spectrum (SOLAR-ISS) is established in April 2008 during the solar minima of cycles 23–24 thanks to revised engineering corrections, improved calibrations, and advanced procedures to account for thermal and aging corrections of the SOLAR/SOLSPEC instrument.Aims. The main objective of this article is to present a new high-resolution solar spectrum with a mean absolute uncertainty of 1.26% at 1σ from 165 to 3000 nm. This solar spectrum is based on solar observations of the SOLAR/SOLSPEC space-based instrument.Methods. The SOLAR/SOLSPEC instrument consists of three separate double monochromators that use concave holographic gratings to cover the middle ultraviolet (UV), visible (VIS), and infrared (IR) domains. Our best ultraviolet, visible, and infrared spectra are merged into a single absolute solar spectrum covering the 165–3000 nm domain. The resulting solar spectrum has a spectral resolution varying between 0.6 and 9.5 nm in the 165–3000 nm wavelength range. We build a new solar reference spectrum (SOLAR-ISS) by constraining existing high-resolution spectra to SOLAR/SOLSPEC observed spectrum. For that purpose, we account for the difference of resolution between the two spectra using the SOLAR/SOLSPEC instrumental slit functions.Results. Using SOLAR/SOLSPEC data, a new solar spectrum covering the 165–3000 nm wavelength range is built and is representative of the 2008 solar minimum. It has a resolution better than 0.1 nm below 1000 nm and 1 nm in the 1000–3000 nm wavelength range. The new solar spectrum (SOLAR-ISS) highlights significant differences with previous solar reference spectra and with solar spectra based on models. The integral of the SOLAR-ISS solar spectrum yields a total solar irradiance of 1372.3 ± 16.9 Wm−2 at 1σ, that is yet 11 Wm−2 over the value recommended by the International Astronomical Union in 2015

FDR4ATMOS (Task B): FDR Long time series for spectral imagers

The Fundamental Data Record for ATMOSpheric Composition (FDR4ATMOS) project is part of the ESA Long Term Data Preservation (LTDP) programme. A Fundamental Data Record (FDR) is a long-term record of selected Earth observation Level 1 parameters (radiance, irradiance, reflectance), possibly multi-instrument, which provides improvements of performance with respect to the individual mission data sets. The aim of task B of the project is to be a pathfinder for future harmonisation of spectrally highly resolved data from other instruments, starting with 2 well known instruments GOME-1 and SCIAMACHY and the spectral ranges for the retrieval of SO2, O3 (UV), NO2 (VIS) and cloud properties (NIR). The FDR will contain harmonised irradiances and reflectances with associated uncertainties. The GOME-1 and SCIAMACHY instruments together span 17 years of spectrally highly resolved data essential for air quality, climate, ozone trend and UV radiation applications. We plan to generate harmonised data sets that allows to directly use it in long-term trend analysis, independently of the instrument. Since this was never done for highly resolved spectrometers, new methods have to be developed that e.g. take into account the different observation geometries for the Earth measurements: GOME-1 and SCIAMACHY had different orbits with a local descending node crossing time of 10:30 and 10:00 respectively resulting in different solar zenith angles. The spatial resolution also differs with GOME-1 having a resolution 40 × 320 km^2 and SCIAMACHY a resolution of 32 × 233 km^2 to 26 × 30 km^2, depending on the spectral range and orbit phase. Since the retrieval of atmospheric trace gas content and other parameters depends on the relative structures of the spectrum, any harmonisation must keep these structures and at the same time take care of broader band differences between the instruments. The data will also contain uncertainties that are based on metrological principles. For that purpose, we reviewed the error sources and error correlations of the original Level 1 data. These uncertainties will flow into the error propagation, leading to final uncertainties of the FDR. The resulting algorithms will be implemented into a processing system using the DLR developed GCAPS framework (Generic Calibration and Processing System). The purpose is to keep the methods and the implementation as generic as possible to be able to easily transfer the methodology to other wavelength ranges and to other instruments (e.g. GOME-2 and Sentinel-5p) for a future extension of the time series. Starting with the solar irradiance as the simpler problem (compared to the Earth radiance measurements) we investigated different methods for the harmonisation and will present the results in the paper. We will also describe the overall validation concept and the status of the harmonisation of the reflectances

The Status of the FDR4ATMOS Project

The Fundamental Data Record for ATMOSpheric Composition (FDR4ATMOS) project is part of the ESA Long Term Data Preservation (LTDP) programme and has two objectives: First, update the SCIAMACHY processing chain for better Ozone total column data: After the full re-processing of the SCIAMACHY mission with the updated processor versions, the validation showed that the total Ozone column drifted downward by nearly 2% over the mission lifetime. This drift is likely caused by changes in the degradation correction in the Level 1 processor, that led to subtle changes in the spectral structures. These are misinterpreted as an atmospheric signature. FDR4ATMOS updated the Level 0-1 processor accordingly and a full mission re-processing hast started. In an addition to the original plan, we also incorporated lunar data in the SCIAMACHYLevel 1b product. The instrument performed regular lunar observations buiding up a unique 10 year data set of lunar spectra from the UV to the SWIR with moderately high spectral resolution. In the project we calibrated these data. The results show an agreement within the error with other lunar data (e.g. ROLO). The second objective of the FDR4ATMOS project is to develop a cross-instrument Level 1 product for GOME-1 and SCIAMACHY for the UV, VIS and NIR spectral range, with focus on the spectral windows used for O3, SO2, NO2 total column retrieval and the determination of cloud properties. FDR4ATMOS aims to build a Fundamental Data Record (FDR) of Level 1 products, i.e. radiances and reflectances. The GOME-1 and SCIAMACHY instruments together span 17 years of spectrally highly resolved data essential for air quality, climate, ozone trend and UV radiation applications. We plan to generate harmonised data sets that allows to directly use it in long-term trend analysis, independently of the instrument. Since this was never done for highly resolved spectrometers, new methods have to be developed that e.g. take into account the different observation geometries and observation times of the instrument without impacting the spectral structures that are used for the retrieval of the atmospheric species. The resulting algorithms and the processor should also be as generic as possible to be able to easily transfer the methodology to other instruments (e.g. GOME-2 and Sentinel-5p) for a future extension of the time series. We will present the current status of the project, including results for the updated SCIAMACHY processor, the uncertainty analyses and will report the status of the data analysis for the harmonisation of data