Costs and mortality associated with HIV: a machine learning analysis of the French national health insurance database

BACKGROUND: The objective is to characterise the economic burden to the healthcare system of people living with HIV (PLWHIV) in France and to help decision makers in identifying risk factors associated with high-cost and high mortality profiles. DESIGN AND METHOD: The study is a retrospective analysis of PLWHIV identified in the French National Health Insurance database (SNDS). All PLWHIV present in the database in 2013 were identified.  All healthcare resource consumption from 2008 to 2015 inclusive was documented and costed (for 2013 to 2015) from the perspective of public health insurance. High-cost and high mortality patient profiles were identified by a machine learning algorithm. RESULTS: In 2013, 96,423 PLWHIV were identified in the SNDS database, including 3,373 incident cases. Overall, 3,224 PLWHIV died during the three-year follow-up period (mean annual mortality rate: 1.1%). The mean annual per capita cost incurred by PLWHIV was € 14,223, corresponding to a total management cost of HIV of € 1,370 million in 2013. The largest contribution came from the cost of antiretroviral medication (M€ 870; 63%) followed by hospitalisation (M€ 154; 11%). The costs incurred in the year preceding death were considerably higher. Four specific patient profiles were identified for under/over-expressing these costs, suggesting ways to reduce them. CONCLUSION: Even though current therapeutic regimens provide excellent virological control in most patients, PLWHIV have excess mortality. Other factors such as comorbidities, lifestyle factors and screening for cancer and cardiovascular disease, need to be targeted in order to lower the mortality and cost associated with HIV infection

Real life patterns of care and progression free survival in metastatic renal cell carcinoma patients: retrospective analysis of cross-sectional data

Abstract Background Patient characteristics and survival outcomes in randomized trials may be different from those in real-life clinical practice. The objective of this study was to describe treatment pathways, safety, drug costs and survival in patients with metastatic Renal Cell Carcinoma (mRCC) in a real world setting. Methods A retrospective analysis was performed using IQVIA real world oncology cross-sectional survey data, a retrospective treatment database collecting anonymized patient-level data in Europe. Data on treatment naïve patients with mRCC who received a first-line targeted therapy in France were extracted for the period 2005–2015. Descriptive analyses were performed on treatment patterns, patient characteristics and safety profiles. Progression Free Survival (PFS) was determined using Kaplan-Meier survival analysis. Results One thousand three hundred thirty-one patients with mRCC who received a first-line targeted therapy were included. The male/female sex ratio was 2.5 and 66% of patients were aged > 60 years. 83% of patients had clear cell adenocarcinoma. 83% of patients underwent a surgical procedure, 10% had radiotherapy. In patients who received a first-line targeted therapy, 73% received sunitinib. The mean time from diagnosis to first-line treatment by targeted therapies in patients initially diagnosed with metastatic disease was 3.3 months [95% CI:2.5–4.1]. In patients who received second-line targeted therapy n = 257 (19%), the most frequently observed treatment sequences were sunitinib-everolimus (33%) and sunitinib-sorafenib (27%). Adverse events data were available for 501 patients and adverse events were documented in 70% of patients, most frequently diarrhoea. The overall median PFS was 13 months [95% CI:11.5–16]. Conclusion Patient characteristics were consistent with the literature. Treatment patterns appeared to follow current practice guidelines. Despite some variations, PFS in our study seems to be consistent with findings from other real world studies. Nevertheless, PFS results were higher than those observed in clinical trials. Due to the use of cross-sectional data, PFS in our study should be interpreted with caution

Series: Pragmatic trials and real world evidence : Paper 8 Data collection and management Data collection in Pragmatic Trials

Pragmatic trials can improve our understanding of how treatments will perform in routine practice. In a series of eight papers, the GetReal Consortium has evaluated the challenges in designing and conducting pragmatic trials and their specific methodological, operational, regulatory and ethical implications. The present final paper of the series discusses the operational and methodological challenges of data collection in pragmatic trials. A more pragmatic data collection needs to balance the delivery of highly accurate and complete data with minimizing the level of interference that data entry and verification induce with clinical practice. Further it should allow for the involvement of a representative sample of practices, physicians and patients who prescribe/receive treatment in routine care. This paper discusses challenges that are related to the different methods of data collection and presents potential solutions where possible. No one-size-fits-all recommendation can be given for the collection of data in pragmatic trials, although in general the application of existing routinely used data collection systems and processes seem to best suit the pragmatic approach. However, data access and privacy, the time points of data collection, the level of detail in the data and the lack of a clear understanding of the data collection process were identified as main challenges for the usage of routinely collected data in pragmatic trials. A first step should be to determine to what extend existing healthcare databases provide the necessary study data and can accommodate data collection and management. When more elaborate or detailed data collection or more structured follow-up is required, data collection in a pragmatic trial will have to be tailor-made, often using a hybrid approach utilizing a dedicated electronic case report form (eCRF). In this case the eCRF should be kept as simple as possible to reduce the burden for practitioners and minimize influence on routine clinical practice

Series: Pragmatic trials and real world evidence : Paper 8 Data collection and management Data collection in Pragmatic Trials

Pragmatic trials can improve our understanding of how treatments will perform in routine practice. In a series of eight papers, the GetReal Consortium has evaluated the challenges in designing and conducting pragmatic trials and their specific methodological, operational, regulatory and ethical implications. The present final paper of the series discusses the operational and methodological challenges of data collection in pragmatic trials. A more pragmatic data collection needs to balance the delivery of highly accurate and complete data with minimizing the level of interference that data entry and verification induce with clinical practice. Further it should allow for the involvement of a representative sample of practices, physicians and patients who prescribe/receive treatment in routine care. This paper discusses challenges that are related to the different methods of data collection and presents potential solutions where possible. No one-size-fits-all recommendation can be given for the collection of data in pragmatic trials, although in general the application of existing routinely used data collection systems and processes seem to best suit the pragmatic approach. However, data access and privacy, the time points of data collection, the level of detail in the data and the lack of a clear understanding of the data collection process were identified as main challenges for the usage of routinely collected data in pragmatic trials. A first step should be to determine to what extend existing healthcare databases provide the necessary study data and can accommodate data collection and management. When more elaborate or detailed data collection or more structured follow-up is required, data collection in a pragmatic trial will have to be tailor-made, often using a hybrid approach utilizing a dedicated electronic case report form (eCRF). In this case the eCRF should be kept as simple as possible to reduce the burden for practitioners and minimize influence on routine clinical practice

Additional file 1: of Real life patterns of care and progression free survival in metastatic renal cell carcinoma patients: retrospective analysis of cross-sectional data

Figure S1. Flow chart of included patients. Table S2. Table resuming patients ‘characteristics. Table S3. Table resuming adverse event data by first-line treatment. (DOCX 37 kb

Dialkoxycarbenes in (4 + 1) Cycloadditions: Application to the Synthesis of Carotol

Dialkoxycarbenes are more reactive than NHCs and participate in many reactions including a formal (4 + 1) cycloaddition with electron-deficient dienes. We have learned to control the relative stereochemistry of the newly created chiral carbons in this process and now report that, combined with a chiral auxiliary, it has been used successfully in a short and efficient synthesis of the sesquiterpene carotol