The cancer premium – explaining differences in prices for cancer vs non-cancer drugs with efficacy and epidemiological endpoints in the US, Germany, and Switzerland: a cross sectional study

Background: High treatment prices of new cancer drugs are a global public health challenge to patients and healthcare systems. Policymakers in the US and Europe are debating reforms to drug pricing. The objective of this study was to assess whether drug efficacy or epidemiological characteristics (prevalence, incidence, mortality) explain the gap in treatment prices between cancer and non-cancer drugs in the US, Germany, and Switzerland. Methods: This cross-sectional study identified all new drugs approved in the US, Germany, and Switzerland between 2011 and 2020. Drug efficacy was extracted from pivotal trials, drug prices from public and commercial databases, and epidemiological characteristics from the Global Burden of Disease (GBD) 2019 study. We used regression models to explain drug prices with drug efficacy and epidemiological characteristics (prevalence, incidence, mortality). Findings: The cohort included 181 drugs, including 68 (37.5%) drugs approved for treatment of cancer. A significant negative correlation was found between incidence/prevalence and treatment prices, and a significant positive correlation was observed between mortality and treatment prices for both, cancer and non-cancer drugs. A significant association between relative drug efficacy and treatment prices of drugs was observed, however, less pronounced for cancer drugs. Our regression estimates indicated that after adjusting for efficacy and epidemiological characteristics, cancer drugs were on average approximately three times more expensive compared to non-cancer drugs in all three countries, indicating a cancer premium; i.e., treatment prices of cancer drugs were on average USD 74,412 (95% CI [62,810; 86,015]) more expensive in the US compared to non-cancer drugs, USD 37,770 (95% CI [26,175; 49,367]) more expensive in Germany, and USD 32,801 (95% CI [27,048; 38,555]) more expensive in Switzerland. Our model explained 72% of the variance in observed prices (R2). Interpretation: Drug pricing reforms should target the cancer premium to improve access of patients to cancer drugs as well as to achieve equity across the different therapeutic areas and sustainability in the health care systems

Исследование закономерностей развития структурно-химической неоднородности в разнородном сварном соединении трубопроводного переходника

Данная работа посвящена исследованию структурно-химической неоднородности (СХН) трубопроводного переходника из разнородных сталей, выполненного аргонодуговой сваркой (АрДС). При помощи оптического микроскопа получены фотографии СХН и ее размеры. СХН выражается в появлении прослоек (карбидной и ферритной) с разным химическим составом. Приведены графики роста ширин прослоек от времени выдержки и температуры.This paper is devoted to the comparison of the structural and chemical inhomogeneity (SCI) of adapters made of dissimilar steels, made by tungsten insert gas (TIG). By means of optical microscope, photographs of the SCI and its dimensions were obtained. SCI is expressed in the appearance of interlayers (carbide and ferritic) with different chemical composition. Graphs of the growth of the widths of the interlayers from the time of exposure and temperature are given

Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1

Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver–kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver–kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22–48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria

Normative data on the Bonn Risk Index for calcium oxalate crystallization in healthy children

Bonn Risk Index (BRI) is being used for the assessment of urinary calcium oxalate (CaOx) crystallization. There are no published data regarding BRI during growth. The objective of this study was to establish age- and sex-dependent BRI values in healthy children and adolescents. A total of 1,050 Caucasian subjects aged 3–18 years (525 males, 525 females) without a history of kidney stone disease were enrolled in the cross-sectional study. The study group was divided into 15 ranges according to age, each comprising 70 subjects. Urinary ionized calcium [Ca(2+)] was measured using a selective electrode while the onset of spontaneous crystallization was determined using a photometer and titrating with 40 mmol/L ammonium oxalate (Ox(2−)). The calculation of BRI value was based on the ratio of [Ca(2+)] to the required amount of ammonium oxalate added to 200 ml of urine to induce crystallization. The median BRI was 0.26 1/L and the values of the 5th and 95th percentiles were 0.06 1/L and 1.93 1/L, respectively. BRI correlated positively with body-area-related BRI (1/L × 1.73 m(2)) (R = 0.18; P < 0.05), whereas a negative correlation was found between BRI and body weight (1/L × kg) (R = −0.85; P < 0.05). Neither sex nor age differences were detected in BRI across studied children and adolescents. The values of Bonn Risk Index were constant during growth and there was a limited influence of age and sex on BRI in children over 3 years of age. The BRI may be valuable in the evaluation of pediatric patients at risk for kidney stones, particularly if the BRI from stone formers is demonstrated to be higher than in normal children

Comparison of uptake and prices of biosimilars in the US, Germany, and Switzerland

Importance: Biologics account for a substantial proportion of health care expenditures. Their costs have been projected to reach US $452 billion in global spending by 2022. Given recent expiration of patent protection of biologics, a shift toward greater follow-on competition among biosimilars would be expected that would allow greater uptake and lower drug costs. Objective: To assess uptake and prices of biosimilars in the US compared with 2 European countries (Germany and Switzerland) with national mechanisms for drug price negotiation. Design, Setting, and Participants: In this cohort study, biologics and biosimilars that were approved in the US, Germany, and Switzerland until August 2020 were identified. Prices and sales data were extracted from public and commercial databases for the years 2011 to 2020. Data were analyzed from August 1, 2021, to February 28, 2022. Main Outcomes and Measures: Descriptive statistics were used to show temporal trends in the uptake of biosimilars and relative prices compared with those of reference products (ie, biologic agents) for each country. Descriptive analysis was also performed to compare the uptake of biosimilars between the 3 countries limited to biologics that have biosimilars on the market in all countries. To test if biosimilar awareness in each country increased over the last decade, a linear least squares regression was applied. Results: The study cohort included 15 biosimilars and 6 biologics for the US, 52 biosimilars and 15 biologics for Germany, and 28 biosimilars and 13 biologics for Switzerland. Uptake of biosimilars increased over time in all countries. On average, the biosimilar market share at launch was highest in Germany; however, it increased at the fastest rate in the US. Monthly treatment costs of biosimilars in the US were a median of 1.94 (IQR, 1.78-2.44) and 2.74 (IQR, 1.91-3.46) higher than corresponding costs in Germany and Switzerland, respectively. Conclusions and Relevance: The findings of this cohort study suggest that more biosimilars have been marketed in Germany and Switzerland than in the US. Policies that counter anticompetitive practices in the US could allow biosimilars to enter the market sooner and could also lower health care costs with improved access. Awareness of biosimilars should be promoted to increase uptake of biosimilars globally

Оценка средней скорости на 10-и метровой глубине для разрезов с высокоскоростным верхним слоем при микрорайонировании

Описываются способы оценки средней скорости поперечной волны на 10-и метровой глубине для разрезов, верхняя часть которых представлена уплотненным насыпным грунтом или мерзлыми породами

Пористая структура продуктов электрохимического синтеза на переменном токе нанодисперсных оксидов олова

Методами электронной микроскопии и низкотемпературной адсорбции азота изучена пористая структура продуктов электролиза металлического олова на переменном токе промышленной частоты. Установлено, что продукты синтеза характеризуются высокими значениями удельной площади поверхности и мезапористой структурой. Показано, что средний размер частиц варьирует в интервале 10…30 нм

Skill and added value of the MiKlip regional decadal prediction system for temperature over Europe

In recent years, several decadal prediction systems have been developed to provide multi-year predictions of the climate for the next 5–10 years. On the global scale, high decadal predictability has been identified for the North Atlantic sector, often extending over Europe. The first full regional hindcast ensemble, derived from dynamical downscaling, was produced within the German MiKlip project (‘decadal predictions’). The ensemble features annual starting dates from 1960 to 2017, with 10 decadal hindcasts per starting year. The global component of the prediction system uses the MPI-ESM-LR and the downscaling is performed with the regional climate model COSMO-CLM (CCLM). The present study focusses on a range of aspects dealing with the skill and added value of regional decadal temperature predictions over Europe. The results substantiate the added value of the regional hindcasts compared to the forcing global model as well as to un-initialized simulations. The results show that the hindcasts are skilful both for annual and seasonal means, and that the scores are comparable for different observational reference data sets. The predictive skill increases from earlier to more recent start-years. A recalibration of the simulation data generally improves the skill further, which can also be transferred to more user-relevant variables and extreme values like daily maximum temperatures and heating degree-days. These results provide evidence of the potential for the regional climate predictions to provide valuable climate information on the decadal time-scale to users