The impact of drug shortages on drug prices: evidence from China.

Introduction: Drug shortages pose a serious global public health challenge, affecting China and other countries. Evidence from USA shows that short-supplied drugs demonstrated a very high price growth during and after a shortage. However, the effect of shortages on drug prices in China remains unknown. This paper aims to understand the impact of drug shortages on prices and explore implications for shortage prevention policy. Methods: We collected the purchase prices and delivery rates of 120 drugs from April 2019 to December 2021 across whole China. We examined price progression of affected drugs using linear mixed-effects models and performed subgroup analyses based on the number of manufacturers and the severity of shortage. Results: Non-shortage cohort had an annual price growth of 11.62% (95% confidence interval [CI] 8.34 to 14.98). Shortage cohort demonstrated an annual price growth of 8.08% (95%CI 0.12 to 16.77) in the period preceding a shortage, 27.57% (95%CI 6.17 to 52.87) during a shortage, and 9.38% (95%CI -12.64 to 36.39) in the post-shortage period. Drug shortages' impact on prices varied across subgroups. Compared with that of drug markets supplied by a single manufacturer, the price growth rate of markets supplied by more than one manufacture declined more after the shortage resolution. Conclusion: Shortages resulted in significant price increases of study markets, especially the low-priced markets, while the shortage resolution slowed the growth. The primary shortage driver has shifted from the low price to others drivers, such as unavailability of active pharmaceutical ingredients. For currently sole-supplied drugs, the expedited review of applications from other manufacturers should be considered.

Evaluation of the effect of managing oxycodone/acetaminophen as a psychotropic medicine: An interrupted time-series study.

Background: Oxycodone/acetaminophen has been reported for misuse for many times in China. To cope with that, Chinese national authorities jointly issued a policy, requiring that oxycodone/acetaminophen should be managed as a psychotropic medicine starting 1 September 2019. This paper aimed to evaluate the effect of this policy in medical institutions. Methods: We used interrupted time-series analysis to examine the immediate level and slope changes in the mean number of tablets prescribed, proportion of oxycodone/acetaminophen prescription exceeding 30 pills, days supplied per prescription and the proportion of days supplied exceeding 10 days with prescription data from 5 tertiary hospitals in Xi'an city between 1 January 2018 and 30 June 2021 (42 months). We divided the prescriptions into two groups, one for long-term drug users, and the other for short-term drug users. Results: In total, 12,491 prescriptions were included in the final study, with 8,941 and 3,550 prescriptions for the short-term and long-term drug users, respectively. Significant differences in the proportion of prescriptions issued by various departments, were observed between pre- and post-implementation of the policy for both short-term and long-term drug users (p < 0.001). For short-term drug users, the policy implementation was only associated with an immediate level decrease in proportion of prescriptions exceeding 30 tablets (-4.09%, p < 0.001). For long-term drug users, after the policy, the mean number of tablets prescribed and the mean proportion of prescriptions exceeding 30 tablets experienced a level decrease of 22.96 tablets (p < 0.001) and a level decrease of 41.13% (p < 0.001), respectively; the mean number of days supplied showed a significant level decrease (6.88 days per prescription) and slope increase (0.19 days per month), and the mean proportion of days supplied exceeding 10 days showed a significant level decrease (-10.51% per prescription) and a slope increase (0.27% per month). Conclusion: Implementation of stricter management for oxycodone/acetaminophen achieved its goal of reducing the risk of misuse in short-term drug users. For those long-term drug users, policy needed to be strengthened as the prescription exceeding 10 days was still at a high level after the intervention. Policies targeting patients with different drug demands are needed. Many other strategies can be implemented, including establishing specific guidelines/principles and conducting training programs.

Procurement of medicines to treat cancer, 2015-2020, China.

Objective: To assess the procurement of medicines to treat cancer in China. Methods: We conducted a descriptive analysis of the national procurement data for 20 anti-cancer medicines in China from 2015 to 2020. We estimated the number of defined daily doses procured per year in three areas of China for essential medicines and medicines for targeted therapies. We adjusted the data by the number of cancer patients in each region for each year. Findings: Between 2015 and 2020, the number of defined daily doses per patient decreased from 40.87 to 35.86 (-12.27%) for essential medicines, while the number increased from 0.85 to 12.52 (1381.15%) for target medicines. The procurement of three out of 10 essential medicines decreased, whereas procurement of all 10 targeted medicines increased. In 2020, the eastern area procured the most essential medicines (44.98 doses per patient) and targeted medicines (16.55 doses per patient), but had the smallest relative change in procurement of both essential medicines (-22.76%) and targeted medicines (978.16%). The central area had the largest increase in procurement of both essential medicines (9.64%; from 25.25 to 27.68 doses per patient) and targeted medicines (4587.81%; from 0.23 to 10.64 doses per patient). Conclusion: Procurement of anti-cancer medicines varied across regions. Specific policies are needed at the national level to eliminate inequalities in access to these medicines. Two issues that need attention are the lower access to many essential anti-cancer medicines in some provinces and the increase in use of targeted medicines.

An overview on the green synthesis and removal methods of pyridaben.

Pyridaben is an acaricide widely used around the world to control phytophagous mites, white flies, aphids, and thrips. It is highly toxic to nontarget organisms such as predatory mites, bees, and fishes. Therefore, the occurrence and removal of pyridaben in food and the environment are worthy of concern. This mini-review focuses on pyridaben residue levels in crops, aquatic systems, and soils, as well as the green synthesis and removal of pyridaben. During the period of 2010-2022, pyridaben was reported in monitoring studies on fruits, vegetables, herbs, bee products, aquatic systems, and soils. Vegetable and agricultural soil samples exhibited the highest detection rates and residue levels. One-pot synthesis offers a green chemistry and sustainable alternative for the synthesis of pyridaben. Among traditional home treatments, peeling is the most effective way to remove pyridaben from crops. Magnetic solid-phase extraction technology has emerged as a powerful tool for the adsorption and separation of pyridaben. Photocatalytic methods using TiO2 as a catalyst were developed as advanced oxidation processes for the degradation of pyridaben in aqueous solutions. Current gaps in pyridaben removal were proposed to provide future development directions for minimizing the exposure risk of pyridaben residues to human and nontarget organisms.

Kinetics of the photolysis of pyridaben and its main photoproduct in aqueous environments under simulated solar irradiation.

The photolytic fate of pyridaben and its main photolysis product was investigated in different aqueous solutions. Results showed that the photolysis of pyridaben followed pseudo first-order kinetics or the hockey-stick model. In buffer solutions, the half-life of pyridaben was the shortest at pH 4, while the degradation rate within 24 h was the highest at pH 9. Humic acids (HA) at concentrations of 1-20 mg L-1 favored the photolysis of pyridaben while fulvic acids (FA) did not have a significant effect. Nitrate at low concentrations (0.01 mM) accelerated the photolysis and Fe(iii) at high concentrations (0.01 and 0.1 mM) significantly inhibited the photolysis. The photolysis rate of pyridaben in rainwater, tap water, and river water was significantly higher than that in distilled water. The half-lives in distilled water, rainwater, tap water, river water, and pond water were 2.36, 1.36, 1.61, 1.77, and 2.68 h, respectively. Ultra-high-performance liquid chromatography/high-resolution mass spectrometry identified M328 as a photolysis product. The degradation of M328 followed pseudo first-order kinetics in distilled water, buffer solutions and aqueous solutions fortified with HA. The half-lives of M328 were in the range of 7.07-13.95 h. These results are essential for further environmental risk assessment of pyridaben.

Combined Experimental and Computational Study on the Transformation of a Novel 1,3,4-Oxadiazole Thioether Nematicide in Aqueous Solutions.

It has been demonstrated that Exianliuyimi (EXLYM) exhibits good nematocidal activity. As a potential nematicide, EXLYM and its transformation products (TPs) may generate emerging pollutants with hazardous effects on the ecosystem. In this study, the fate of EXLYM in aqueous solutions was investigated using experimental and theoretical approaches. Laboratory-scale experiments showed that EXLYM is hydrolytically stable. Microbial processes are primarily responsible for the oxidation of sulfur in aqueous solutions. Under simulated sunlight, the t1/2 values of EXLYM in acidic, neutral, and alkaline buffer solutions were 5.02, 3.83, and 5.55 h, respectively. Six TPs were identified using a non-target screening strategy realized by ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap high-resolution mass spectrometry and 18O-labeling experiments. Four of these were unambiguously confirmed using authentic standards. Reactive oxygen species scavenging experiments, 18O-labeling experiments, and quantum-theoretical calculations suggested that EXLYM could degrade mainly through four pathways: sulfur oxidation, nucleophilic aromatic photosubstitution, C-S bond cleavage, and oxidative ring-opening. The proposed degradation kinetics, TPs, and transformation pathways in aqueous solutions provide valuable information on the fate of EXLYM in aquatic ecosystems and lay the foundation for further toxicological tests.

Regio- and Steric Effects on Single Molecule Conductance of Phenanthrenes.

Here, six phenanthrene (the smallest arm-chair graphene nanoribbon) derivatives with dithiomethyl substitutions at different positions as the anchoring groups were synthesized. Scanning tunneling microscopy break junction technique was used to measure their single molecule conductances between gold electrodes, which showed a difference as much as 20-fold in the range of ∼10-2.82 G0 to ∼10-4.09 G0 following the trend of G2,7 > G3,6 > G2,6 > G1,7 > G1,6 > G1,8. DFT calculations agree well with this measured trend and indicate that the single molecule conductances are a combination of energy alignment, electronic coupling, and quantum effects. This significant regio- and steric effect on the single molecule conductance of phenanthrene model molecules shows the complexity in the practice of graphene nanoribbons as building blocks for future carbon-based electronics in one hand but also provides good conductance tunability on the other hand.

Perceptions of pharmacists towards drug shortages in the healthcare system of Pakistan and its impact on patient care: findings from a cross-sectional survey.

OBJECTIVE: This study aimed to explore pharmacists' perceptions on drug shortages and its impingement on the Pakistani healthcare system, in particular on patient care. DESIGN: Online questionnaire survey. SETTING AND PARTICIPANTS: Hospital pharmacists from five out of seven regions of Pakistan were approached; including the federal territory (Islamabad) and four provinces (Khyber Pakhtunkhwa, Balochistan, Punjab and Sindh). PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence and type of shortages were identified along with strategies to reduce its effect on patient care. METHOD: A validated questionnaire was distributed through various online platforms to 800 registered hospital pharmacists. A convenience sampling technique was used to obtain information on drug shortages, the reporting system for shortages, the impact on patients and policy solutions for managing drug shortages. RESULTS: Out of 800 hospital pharmacists, 708 completed the questionnaire (response rate: 88.5%). Of these hospital pharmacists, 47% came from hospitals of Punjab, 26% from Khyber Pakhtunkhwa, 13% from Sindh, 11% from Balochistan and 4% from Islamabad; 72% and 28% worked in tertiary and secondary hospitals, respectively. The majority (32%) interacted with shortages daily. The top three drug categories reported in shortage were oncology drugs (54%), cardiovascular drugs (53%) and antimicrobials (42%). 58% of the respondents have seen care delayed as a negative consequence of shortages. 'Creating new communication system' (65%) and 'readjust budget plans' (41%) were the two most frequently indicated recommendations for shortages management at hospital, while 'circulars or alerts from the regulatory authority' (60%) and 'time to time directives from local health statuaries' (48%) were two most widely suggested policy solutions. CONCLUSION: Drug shortage is a serious concern in Pakistani hospitals, experienced on a daily basis endangering patients' health. Enhanced communication is required, connecting the key stakeholders. Health policies should be reviewed; adequate funds should be allocated to the health sector preventing future shortages.

Clinical Consumption of Compound Opioid Analgesics in China: A Retrospective Analysis of National Data 2015-2018.

Compound opioid analgesics (COA) are widely used for cancer pain relief, but few studies investigated the use of that. We aimed to report the characteristics and trend of COA consumption in different regions and health facilities in China. The procurement data of two types of COA, compound codeine phosphate (CCP) and oxycodone and acetaminophen (OAA), in all medical institutions of 20 provinces from 2015 to 2018 were used. Data were presented as defined daily dose for statistical purpose (SDDD) and expenditures per million inhabitants per day. The annual consumption of COA and ratio of two combinations were compared among regions and institutions. We found, during 2015-2018, COA consumption increased at an average rate of 7.32% in SDDD and 19.19% in expenditures, while OAA accounted for most of the consumption. Highest COA consumption appeared in Northern China, with 121.72 SDDD and 1689.87 RMB (2015), whereas the lowest COA consumption was only 11.28 SDDD appearing in Southern China. The ratio of OAA and CCP (in SDDD) was highest in Southern China (53.14 in 2018), whereas lowest in West North (0.37 in 2018). In terms of institutions, tertiary had the highest COA consumption, with 16.74 SDDD and 292.73 RMB (2018). The SDDD of OAA was 27.44 times of that of CCP in tertiary, while it was only 0.11 in primary. Overall, COA consumption is on an upward trend and different among regions and health institutions in either amount or types of COA. These findings call for establishment of COA management regulations.