AIMS: We aimed to explore atrial fibrillation (AF)-induced productivity losses in working-age atrial fibrillation patients and to estimate atrial fibrillation-related indirect costs. METHODS: Between 2014 and 2017, the Swiss Atrial Fibrillation prospective cohort study (Swiss-AF) enrolled 217 working-age patients with documented atrial fibrillation. Self-reported changes in professional activity and the reasons thereof were descriptively analysed over 8 years of follow-up or until patients reached the retirement age. Results were put into perspective, and indirect costs were planned to be estimated, through comparison with a general population-based, age-, sex- and year-matched comparison sample from the Swiss labour force survey (SLFS). RESULTS: Of 217 analysed Swiss-AF patients, 14.7% reported a professional activity change (9.2% stop, 5.5% reduction) due to atrial fibrillation before the end of observation. Of those working at enrolment (n = 157), 3.8% had a subsequent professional activity change due to atrial fibrillation, 11.6% due to other reasons. Patients were more likely to report an impact of atrial fibrillation on professional activity if they had had atrial fibrillation longer and were closer to the retirement age. Slightly fewer Swiss-AF patients were employed (75%) than in the comparison sample (77%). For those working however, the degree of employment was higher (88% vs 83%). Lack of differences between the Swiss-AF patients and the comparison sample indicated no relevant indirect costs of atrial fibrillation due to lost productivity. CONCLUSION: Only a minority of atrial fibrillation patients reported a negative impact of atrial fibrillation on their professional activity. Professional activity changes due to other reasons were reported more frequently. Compared with the general population, atrial fibrillation did not cause distinct differences.

Importance There are no useful treatments to prevent the development of severe complications of liver cirrhosis. Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis. Objective To assess whether simvastatin combined with rifaximin improves outcomes in patients with decompensated cirrhosis. Design, Setting, and Participants Double-blind, placebo-controlled, phase 3 trial conducted among patients with decompensated cirrhosis in 14 European hospitals between January 2019 and December 2022. The last date of follow-up was December 2022. Interventions Patients were randomly assigned to receive simvastatin, 20 mg/d, plus rifaximin, 1200 mg/d (n = 117), or identical-appearing placebo (n = 120) for 12 months in addition to standard therapy, stratified according to Child-Pugh class B or C. Main Outcomes and Measures The primary end point was incidence of severe complications of liver cirrhosis associated with organ failure meeting criteria for acute-on-chronic liver failure. Secondary outcomes included transplant or death and a composite end point of complications of cirrhosis (ascites, hepatic encephalopathy, variceal bleeding, acute kidney injury, and infection). Results Among the 237 participants randomized (Child-Pugh class B: n = 194; Child-Pugh class C: n = 43), 72% were male and the mean age was 57 years. There were no differences between the 2 groups in terms of development of acute-on-chronic liver failure (21 [17.9%] vs 17 [14.2%] patients in the treatment and placebo groups, respectively; hazard ratio, 1.23; 95% CI, 0.65-2.34; P = .52); transplant or death (22 [18.8%] vs 29 [24.2%] patients in the treatment and placebo groups, respectively; hazard ratio, 0.75; 95% CI, 0.43-1.32; P = .32); or development of complications of cirrhosis (50 [42.7%] vs 55 [45.8%] patients in the treatment and placebo groups, respectively; hazard ratio, 0.93; 95% CI, 0.63-1.36; P = .70). Incidence of adverse events was similar in both groups (426 vs 419; P = .59), but 3 patients in the treatment group (2.6%) developed rhabdomyolysis. Conclusions and Relevance The addition of simvastatin plus rifaximin to standard therapy does not improve outcomes in patients with decompensated liver cirrhosis.

Cancer drugs have accumulated the most approvals over the past years. Overall survival (OS) is considered the gold standard for cancer trial outcomes. However, its use has declined over the past years, in favor of surrogate endpoints, such as progression-free survival (PFS). PFS allows to assess outcomes earlier and, thus, accelerates approval of cancer drugs. Previous studies have demonstrated a poor correlation between PFS and OS. Using simulation models, we examined why PFS usually overestimates survival benefit. We created a publicly accessible web application that allows users to run the simulations with different parameter settings. Based on the findings, we propose that assessment of preliminary evidence should be based on a combination of OS result and prognostic scores that reflect the health status of surviving patients.

Many countries have incorporated population screening programmes for cancer, such as colorectal and lung cancer, into their health-care systems. Cirrhosis is more prevalent than colorectal cancer and has a comparable age-standardized mortality rate to lung cancer. Despite this fact, there are no screening programmes in place for early detection of liver fibrosis, the precursor of cirrhosis. In this Perspective, we use insights from colorectal and lung cancer screening to explore the benefits, challenges, implementation strategies and pathways for future liver fibrosis screening initiatives. Several non-invasive methods and referral pathways for early identification of liver fibrosis exist, but in addition to accurate detection, screening programmes must also be cost-effective and demonstrate benefit through a reduction in liver-related mortality. Randomized controlled trials are needed to confirm this. Future randomized screening trials should evaluate not only the screening tests, but also interventions used to halt disease progression in individuals identified through screening.

AIMS: To explore the effects of prices and flavour availability on the appeal of different tobacco and nicotine products, including conventional cigarettes, Electronic Nicotine Delivery Systems (ENDS) and Heated Tobacco Systems (HTS) among an adult population in Switzerland. METHODS: We performed a Discrete Choice Experiment among a group of Swiss aged ≥18 years via the online recruiting platform Prolific in a convenience sample. Our sample included both non-smokers and smokers. We used a within-subject, alternative-specific block design in a series of choice sets including different smoking products. We fixed the attributes of nicotine content (high or medium) and harmfulness (in years of life lost) for each product. Attributes of interest included price (ranging from CHF 5 to 25 in increments of 5) and flavour (fruity/menthol vs none/tobacco flavour). We performed a conditional logistic regression on the attributes’ influence on the appeal of cigarettes, ENDS and HTS. RESULTS: A total of 108 out of 153 participants (n = 25 smokers and n = 83 non-smokers, completion rate = 71%) successfully completed our pilot survey experiment. We found that, in general, increasing the price of combustible cigarettes, ENDS and HTS by one standard deviation (around CHF 7) reduced their appeal by approximately 66% (relative risk [RR]: 0.34; 95% CI: 0.28–0.42). Unflavoured alternative nicotine products were found to be less appealing than flavoured products, especially for non-smokers, with a 86% decrease in appeal (RR: 0.14; 95% CI: 0.13–0.16). For non-smokers, an increase in price by one standard deviation was associated with a decrease in the appeal of any product by approximately 19% (RR: 0.81; 95% CI: 0.72–0.92). For smokers, the effect sizes were smaller, but overall, the appeal of all products decreased with increasing prices and reduced flavours. CONCLUSIONS: Our Discrete Choice Experiment suggests that, for the Swiss context, limiting the availability of flavours for alternative smoking products has the potential to reduce their appeal to non-smokers by 86% and that a small but significant increase in prices to CHF 15 for cigarettes, ENDS and HTS could lead to a major (around 66%) decrease in their appeal.

Download This Paper Open PDF in Browser Add Paper to My Library Share: Permalink Using these links will ensure access to this page indefinitely Copy URL Copy DOI

Importance:High prices of new drugs are concerning. What remains to be understood are price developments after entering the market because not only initial prices, but also postlaunch prices, contribute to drug spending. Objective:To analyze launch and postlaunch price developments of new drugs in the US, Germany, and Switzerland. Design, Setting, and Participants:This cohort study used the public databases of the US Food and Drug Administration, European Medicines Agency, and Swissmedic to identify all new drugs approved between January 2011 and December 2022. Data were collected and analyzed between January 2024 and September 2024. During the revision process in October 2024, SSR data were also analyzed. Drugs for which price data were available were included in the study cohort. Launch prices and postlaunch price developments in the US, Germany, and Switzerland were calculated from 2011 until 2023. Main Outcomes and Measures:Standard statistics (mean, median, and IQR) were applied to analyze launch drug prices and postlaunch drug price developments over time in the US, Germany, and Switzerland. Results:The cohort study included 254 drugs in the US, 298 in Germany, and 235 in Switzerland. In the US, mean (SD) launch prices increased from $31 699 ($36 439) in 2011 to $228 658 ($571 252) in 2022, with an average increase of 19.7% per year. In Germany, mean (SD) launch prices increased from $77 237 ($228 672) to $146 072 ($306 091), with an average increase of 6.0% per year. In Switzerland, mean launch prices increased from $29 211 ($41 919) to $41 399 ($39 697), with an average increase of 3.2% per year. Post launch, trimmed mean prices of included drugs in the study cohort increased -0.6% at 3 years, 2.4% at 5 years, and 4.1% at 10 years post launch in the US. A larger increase of postlaunch prices was observed for cancer drugs compared with noncancer drugs. In Germany, trimmed mean drug prices decreased -30.9% at 3 years, -33.4% at 5 years, and -45.2% at 10 years post launch. In Switzerland, trimmed mean drug prices decreased -9.3% at 3 years, -13.5% at 5 years, and -29.5% at 10 years post launch. In Switzerland and Germany, postlaunch price developments were similar for cancer and noncancer drugs, but treatment costs of cancer drugs remained substantially higher compared with noncancer drugs. Conclusions and Relevance:The results of this cohort study suggest that, in contrast to Germany and Switzerland, prices of cancer drugs increased substantially post launch in the US. When developing solutions how drug prices can be decreased, launch as well as postlaunch prices require attention from policymakers.

The value of adding fusion to decompression surgery for lumbar degenerative spondylolisthesis and spinal canal stenosis remains debated. Therefore, the comparative effectiveness and selected healthcare resource utilization of patients undergoing decompression with or without fusion surgery at 3 years follow-up was assessed. Using observational data from the Lumbar Stenosis Outcome Study and a target trial emulation with index trial benchmarking approach, our study assessed the comparative effectiveness of the two main surgical interventions for lumbar degenerative spondylolisthesis—fusion and decompression alone in patients with lumbar degenerative spondylolisthesis and spinal canal stenosis. The primary outcome-measure was change in health-related quality of life (EuroQol Health Related Quality of Life 5-Dimension 3-Level questionnaire [EQ-5D-3L]); secondary outcome measures were change in back/leg pain intensity (Numeric Rating Scale), change in satisfaction (Spinal Stenosis Measure satisfaction subscale), physical therapy and oral analgesic use (healthcare utilization). 153 patients underwent decompression alone and 62 had decompression plus fusion. After inverse probability weighting, 137 patients were included in the decompression alone group (mean age, 73.9 [7.5] years; 77 female [56

Aims Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment.Methods The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment.Results 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained.Conclusions Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.

This article analyzes trends in drug shortages in the US and Germany, the largest pharmaceutical market in Europe, between 2016 and 2023. It assesses the commonalities and differences between the countries in terms of active substances in shortage, time duration in shortage, and cyclic trends.

Importance Understanding how patent expirations affect drug prices is crucial because price changes directly inform accurate cost-effectiveness assessments. This study investigates the association between patent expirations and drug prices in 8 high-income countries and evaluates how the changes affect cost-effectiveness assessments. Objective To analyze how the expiration of drug patents is associated with drug price changes and to assess the implications of these price changes for cost-effectiveness evaluations. Design, Setting, and Participants This cohort study performed an event study design using data from 8 high-income countries to assess the association between patent expiration and drug prices, and created a simulation model to understand the implications for cost-effectiveness analyses. The simulation cost-effectiveness model analyzed the implications of including or ignoring postpatent price dynamics. Exposure Drug patent expiration. Main Outcomes and Measures Change in drug prices and differences in incremental cost-effectiveness ratios when considering vs ignoring postpatent price dynamics. Results The sample comprised 505 drugs undergoing patent expiration in Australia, Canada, France, Germany, Japan, Switzerland, UK, and US. Price decreases were statistically significant over the 8 years after patent expiration, with the fastest price declines observed in the US: 32% (95% CI, 24%-39%) in year 1 after patent expiration and 82% (95% CI, 71%-89%) in the 8 years after patent expiration. Estimates for other nations ranged from a decrease of 64% in Australia to 18% in Switzerland in the 8 years after expiration. The cost-effectiveness simulation model indicated that not accounting for generic entry into the market may produce biased incremental cost-effectiveness ratios of 40% to -40%, depending on the scenario. Conclusions and Relevance The findings of this cohort study demonstrate that drug prices were reduced substantially after patent expirations in high-income countries. Therefore, incorporating information on patent status and pricing dynamics in cost-effectiveness assessment analyses is necessary for producing accurate economic evaluations of new drugs.

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 cor-relation 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. 2023;61: Published 2023 https://doi.org/10. 1016/j.eclinm.2023. 102087

OBJECTIVE To analyze the therapeutic value of supplemental indications compared with first indications for drugs approved in the US and Europe.DESIGN Retrospective cohort study.SETTING New and supplemental indications approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) between 2011 and 2020.MAIN OUTCOME MEASURES Proportion of first and supplemental indications rated as having high therapeutic value using ratings from the French and German national, independent health authorities.RESULTS The cohort study included 124 first and 335 supplemental indications approved by the FDA and 88 first and 215 supplemental indications approved by the EMA between 2011 and 2020; the largest subset was for cancer disorders. Therapeutic ratings were available for 107 (86%) first and 179 (53%) supplemental indications in the US and for 87 (99%) first and 184 (86%) supplemental indications in Europe. Among FDA approved indications with available ratings, 41% (44/107) had high therapeutic value ratings for first indications compared with 34% (61/179) for supplemental indications. In Europe, 47% (41/87) of first and 36% (67/184) of supplemental indications had high therapeutic value ratings. Among FDA approvals, when the sample was restricted to the first three approved indications, second indication approvals were 36% less likely to have a high value rating (relative ratio 0.64, 95% confidence interval 0.43 to 0.96) and third indication approvals were 45% less likely (0.55, 0.29 to 1.01) compared with the first indication approval. Similar findings were observed for Europe and when weighting by the inverse number of indications for each drug.CONCLUSIONS The proportion of supplemental indications rated as having high therapeutic value was substantially lower than for first indications. When first or supplemental indications do not offer added therapeutic value over other available treatments, that information should be clearly communicated to patients and physicians and reflected in the price of the drugs.

Study Design. A post hoc analysis. Objective. Advances in machine learning (ML) have led to tools offering individualized outcome predictions for adult spinal deformity (ASD). Our objective is to examine the properties of these ASD models in a cohort of adult symptomatic lumbar scoliosis (ASLS) patients. Summary of Background Data. ML algorithms produce patient-specific probabilities of outcomes, including major complication (MC), reoperation (RO), and readmission (RA) in ASD. External validation of these models is needed. Methods. Thirty-nine predictive factors (12 demographic, 9 radiographic, 4 health-related quality of life, 14 surgical) were retrieved and entered into web-based prediction models for MC, unplanned RO, and hospital RA. Calculated probabilities were compared with actual event rates. Discrimination and calibration were analyzed using receiver operative characteristic area under the curve (where 0.5=chance, 1=perfect) and calibration curves (Brier scores, where 0.25=chance, 0=perfect). Ninety-five percent confidence intervals are reported. Results. A total of 169 of 187 (90%) surgical patients completed 2-year follow up. The observed rate of MCs was 41.4% with model predictions ranging from 13% to 68% (mean: 38.7%). RO was 20.7% with model predictions ranging from 9% to 54% (mean: 30.1%). Hospital RA was 17.2% with model predictions ranging from 13% to 50% (mean: 28.5%). Model classification for all three outcome measures was better than chance for all [area under the curve=MC 0.6 (0.5–0.7), RA 0.6 (0.5–0.7), RO 0.6 (0.5–0.7)]. Calibration was better than chance for all, though best for RA and RO (Brier Score=MC 0.22, RA 0.16, RO 0.17). Conclusions. ASD prediction models for MC, RA, and RO performed better than chance in a cohort of adult lumbar scoliosis patients, though the homogeneity of ASLS affected calibration and accuracy. Optimization of models require samples with the breadth of outcomes (0%–100%), supporting the need for continued data collection as personalized prediction models may improve decision-making for the patient and surgeon alike.

Objectives: Compare patient selection and postoperative outcomes after surgical treatment for gastrointestinal disorders before and during the SARS-CoV-2 pandemic. Methods: We assessed gastrointestinal surgeries conducted at a tertiary center from 2017–2021 for differences in patient populations and procedures before (up to February 2020) and during the pandemic (March 2020 to December 2021). We analyzed mortality, Intensive Care Unit (ICU) length of stay, admission to ICU and postoperative complications for complex procedures using descriptive statistics and regression models. Results: 7309 procedures were analyzed, showing a caseload reduction in March and October 2020, but no statistical evidence for fewer overall procedures overall. Population characteristics differed with lower Body Mass Indices in 2020 and 2021, more patients smoking and with diabetes treated in 2020. There was no increased mortality, ICU length of stay and in 1,144 complex procedures assessed low overall morbidity at 90 days postoperative. Conclusion: Delivering surgical care while treating patients for COVID-19 in the same hospital was safe. Healthcare officials should consider continuing surgical care during future health crises as consequences of limiting surgical treatment for gastrointestinal disorders may be fatal for patients.