Degarelix vs. leuprorelin for the treatment of prostate cancer in China: A cost-utility analysis

ObjectiveTo explore the cost-effectiveness of degarelix acetate for injection (degarelix) compared to leuprorelin in prostate cancer (Pca) castration treatment from Chinese healthcare system perspective.MethodsA Markov model, adapted from the one established in Finland was conducted for the cost-effectiveness analysis of degarelix and leuprorelin for Pca treatment. The main data were derived from global phase III clinical trials of degarelix (CS21), published study and expert surveys. Outcomes, utility and costs of prostate cancer patients were calculated on a 30-year time horizon. The CS21 study based population of intention-to-treat (ITT) population and three scenarios were modeled. Taking three times of the Gross domestic product (GDP) per capita (242,928 yuan, 2021) as the acceptable threshold for cost-effectiveness. One-way and probabilistic sensitivity analyses were performed on key parameters, including transition probabilities, costs, utility, and discount rate to test the robustness of the model.ResultsBase case analysis for ITT population revealed that total costs of degarelix and leuprorelin were 566,226 yuan and 489,693 yuan, while the total quality-adjusted life years (QALYs) were 5.19 and 4.51 during the 30-year time horizon, resulting an incremental cost effectiveness ratio (ICER) of 112,674 yuan/QALY which was 1.39 times the GDP per capita, lower than willingness-to-pay level of three times the GDP per capita. The results for scenario analyses revealed that compared to leuprorelin, degarelix for Pca treatment in China was cost-effective. One-way sensitivity analysis showed that the model was most sensitive to price of 80 mg degarelix, utility of 1st-line therapy, hazard ratio of PSA recurrence, price of 3.75 mg leuprorelin, response rate of docetaxel per cycle, and discount rate of cost. In probabilistic sensitivity analysis, compared to leuprorelin, the probability of degarelix to be cost-effective was 53 and 81% for willingness-to-pay threshold of one and three times the GDP per capita.ConclusionCompared to leuprorelin, degarelix for prostate cancer treatment is cost-effective. Moreover, scenario, one-way, and probabilistic sensitivity analyses revealed that the model was robust

On confidence intervals for the hazard ratio in randomized clinical trials: On Confidence Intervals for the Hazard Ratio in Randomized Clinical Trials

The log-rank test is widely used to compare two survival distributions in a randomized clinical trial, while partial likelihood (Cox, 1975) is the method of choice for making inference about the hazard ratio under the Cox (1972) proportional hazards model. The Wald 95% confidence interval of the hazard ratio may include the null value of 1 when the p-value of the log-rank test is less than 0.05. Peto et al. (1977) provided an estimator for the hazard ratio based on the log-rank statistic; the corresponding 95% confidence interval excludes the null value of 1 if and only if the p-value of the log-rank test is less than 0.05. However, Peto’s estimator is not consistent, and the corresponding confidence interval does not have correct coverage probability. In this paper, we construct the confidence interval by inverting the score test under the (possibly stratified) Cox model, and we modify the variance estimator such that the resulting score test for the null hypothesis of no treatment difference is identical to the log-rank test in the possible presence of ties. Like Peto’s method, the proposed confidence interval excludes the null value if and only if the log-rank test is significant. Unlike Peto’s method, however, this interval has correct coverage probability. An added benefit of the proposed confidence interval is that it tends to be more accurate and narrower than the Wald confidence interval. We demonstrate the advantages of the proposed method through extensive simulation studies and a colon cancer study

Evaluation of marketing authorization and labels of medicines in 2021 WHO Model List of Essential Medicines for Children in China, the Russian Federation and Brazil

Abstract Objective This work compares the marketing authorization, labels and dosage forms of medicines in the WHO Model List of Essential Medicines for Children (EMLc) in China, the Russian Federation and Brazil to urge policymakers to pay more attention to paediatric medication. Methods Medicines were selected from the 8th EMLc. By searching relevant databases, which include different types of medical information in China, the Russian Federation and Brazil, the marketing authorization, labels and dosage forms of paediatric medicines in the three countries were evaluated. Results A total of 485 drug products containing 312 active pharmaceutical ingredients listed in the WHO EMLc were evaluated. Among them, 344 products were approved for use in China, 286 in the Russian Federation and 264 in Brazil. Out of the 344 approved medicines, 317 (92.15%) were authorized for paediatric use in China, 224 (78.32%) in the Russian Federation and 218 (82.58%) in Brazil. In terms of guidance information labelling on drug labels, 75.08%, 83.04% and 88.07% of paediatric drugs approved in China, the Russian Federation and Brazil, respectively, clearly indicated the usage and dosage for paediatric use. Additionally, injections and tablets were the most prevalent dosage forms in these three countries. Conclusion There is still scope for enhancing the marketing authorization and development of dosage forms for paediatric medicines in the three countries. Furthermore, additional measures are being implemented to enhance the information provided on drug labels for children, particularly in China

The Consistency Between the Chinese Essential Medicines List and Treatment Guidelines—Taking Oncology Medicines as an Example

The concepts of “essential medicine” and “national medicine policy” were first put forward for the first time at the World Health Assembly in 1975 in an effort to alleviate the problem of medicine unavailability in developing and poor countries. The essential medicine system in China has experienced three development stages since 1979, when the concept of essential medicines was first introduced, to actively respond to the call of the World Health Organization. Currently, the essential medicines list published in China is the national essential medicines list (2018 Edition). In this study, we examined the consistency between the essential medicines for treating seven cancers (liver cancer, breast cancer, esophageal cancer, lung cancer, colorectal cancer, gastric cancer, and leukemia) and the recommended medicines by cancer treatment guidelines to determine whether the essential medicines are of high quality for clinical needs. The results indicated that the degree of similarity between oncology medicines on the essential medicines list and oncology medicines recommended by guidelines was low, with the majority falling between 30 and 60%. Therefore, to improve the quality of essential medicines, it is necessary to further improve the matching degree. In addition, to further improve the consistency between the essential medicines list and treatment guidelines, the following suggestions are put forward in this paper: (1). Formulate universal treatment guidelines; (2). When selecting essential medicines, greater consideration should be given to those recommended in the guidelines; (3). The essential medicines list and treatment guidelines should be concurrently updated; (4). The cycle for updating the essential medicines list and treatment guidelines should be shortened.</jats:p

FDSS-Based DFT-s-OFDM for 6G Wireless Sensing

Integrated sensing and communications (ISAC) is emerging as a key technology of 6G. Owing to the low peak-to-average power ratio (PAPR) property, discrete Fourier transform spread orthogonal frequency-division multiplexing (DFT-s-OFDM) is helpful to improve the sensing range and suitable for high-frequency transmission. However, compared to orthogonal frequency-division multiplexing (OFDM), the sensing accuracy of DFT-s-OFDM is relatively poor. In this paper, frequency-domain spectral shaping (FDSS) is adopted to enhance the performances of DFT-s-OFDM including sensing accuracy and PAPR by adjusting the correlation of signals. Specifically, we first establish a signal model for the ISAC system, followed by the description of performance indicators. Then, we analyze the influence of amplitude fluctuation of frequency domain signals on sensing performance, which shows the design idea of FDSS-enhanced DFT-s-OFDM. Further, a FDSS-enhanced DFT-s-OFDM framework is introduced for ISAC, where two types of FDSS filters including a pre-equalization filter and an isotropic orthogonal transform algorithm (IOTA) filter are designed. The simulation results show that the proposed scheme can obtain about 4 dB performance gain in terms of sensing accuracy over DFT-s-OFDM. In addition, FDSS-enhanced DFT-s-OFDM can significantly reduce PAPR and improve the power amplifier efficiency