The impact of National Centralised Drug Procurement policy on the use of policy-related original and generic drugs in China.

AIMS: To evaluate the effects of the first round of National Centralised Drug Procurement pilot (so-called '4+7' policy) on the use of policy-related original and generic drugs. METHODS: This study used drug purchasing order data from the Centralised Drug Procurement Survey in Shenzhen 2019, covering 24 months from January 2018 to December 2019. '4+7' policy-related drugs were selected as study samples, including 25 drugs in the '4+7' procurement list and 69 alternative drugs that have an alternative relationship with '4+7' List drugs in clinical use. '4+7' List drugs were then divided into bid-winning and bid-non-winning products according to the bidding results. Included drugs were sorted into original and generic drugs. Purchase volume, expenditures, and daily costs were selected as outcome variables, and were measured using Defined Daily Doses (DDDs), Chinese Yuan (CNY), and Defined Daily Drug cost (DDDc). A single-group Interrupted Time Series analysis was adopted to quantify policy effect. RESULTS: After policy intervention, the overall policy-related original drugs significantly decreased by 0.39 CNY (95% CI: -0.62 to -0.17, p < 0.01) in DDDc, 5949.36 thousand DDDs (95% CI: -8276.67 to -3622.05, p < 0.001) in volume, and 31,575.08 thousand CNY (95% CI: -41,812.68 to -21,337.49, p < 0.001) in expenditures. The volume proportion of generic drugs increased from 78.6% to 91.0%, and the expenditure proportion of increased from 30.9% to 49.8%. CONCLUSION: '4+7' policy promoted the substitution use of domestic generics against original branded drugs and played positive effects on drug price cut and medication burden reduction. The proportion of original branded drugs and generics that passed generic consistency evaluation significantly increased after policy intervention, indicating the improvement of the overall quality level of drug use in China.

The impact of "4 + 7" volume-based drug procurement on the volume, expenditures, and daily costs of antihypertensive drugs in Shenzhen, China: an interrupted time series analysis.

BACKGROUND: In 2019, Chinese government launched a nationwide volume-based drug procurement aiming at reducing drug prices and saving drug costs through economies of scale, which aroused widespread attention. The first round of the policy pilot was implemented in 4 municipalities and 7 sub-provincial cities, referred to as "4 + 7" policy. In the "4 + 7" policy, 7 antihypertensive drugs were included. This study was conducted to evaluate the impact of "4 + 7" policy on the use of policy-related antihypertensive drugs. METHOD: This study applied single-group Interrupted Time Series (ITS) design. We used drug purchasing data from the Centralized Drug Procurement Survey in Shenzhen 2019, covering 24 months from January 2018 to December 2019. Antihypertensive drugs related to "4 + 7" policy were selected as study samples, including 7 drugs in the "4 + 7" List and 17 alternative drugs. Alternative drugs refer to antihypertensive drugs that have an alternative relationship with "4 + 7" List drugs in clinical use and have not yet been covered by the policy. "4 + 7" List drugs were then divided into bid-winning and bid-non-winning products according to the bidding results. Purchase volume, expenditures, and daily costs were selected as outcome variables, and were measured using Defined Daily Doses (DDDs), Chinese Yuan (CNY), and Defined Daily Drug cost (DDDc). RESULTS: After "4 + 7" policy intervention, the procurement volume of bid-winning antihypertensive drugs significantly increased (3.12 million DDD, 95 % CI = 2.14 to 4.10, p < 0.001), while the volume of non-winning drugs decreased (-2.33 million DDD, 95 % CI= -2.83 to -1.82, p < 0.01). The use proportion of bid-winning antihypertensive drugs increased from 12.31 to 87.74 % after policy intervention. The overall costs of the seven "4 + 7" List antihypertensive drugs significantly declined (-5.96 million CNY, 95 % CI= -7.87 to -4.04, p < 0.001) after policy intervention, with an absolute reduction of 36.37 million CNY compared with the pre-"4 + 7" period. The DDDc of bid-winning antihypertensive drugs significantly decreased (-1.30 CNY, 95 % CI= -1.43 to -1.18, p < 0.001), while the DDDc of non-winning (0.28 CNY, 95 % CI = 0.11 to 0.46, p < 0.01) and alternative (0.14 CNY, 95 % CI = 0.03 to 0.25, p < 0.05) antihypertensive drugs increased markedly. CONCLUSIONS: The implementation of "4 + 7" policy promoted the drug use hypertensive patients gradually concentrated on the quality-guaranteed bid-winning drugs, which might be conducive to improve the overall quality level of drug use of Chinese hypertensive patients. Besides, a preliminary positive policy effect of price cut and cost-saving was observed in the antihypertensive drug category. In the future, price monitoring and drug use management regarding policy-related drugs should also be strengthened.

Impact of '4+7' volume-based drug procurement on the use of policy-related original and generic drugs: a natural experimental study in China.

OBJECTIVE: To evaluate the impact of the first round of the National Centralized Drug Procurement pilot (so-called '4+7' policy) on the use of policy-related original and generic drugs. METHODS: A retrospective natural experimental design was adopted. Drug procurement data from the China Drug Supply Information Platform database were used, involving 9 '4+7' pilot cities in intervention group and 12 non-pilot provinces in control group. '4+7' policy-related drugs were selected as study samples, including 25 drugs in the '4+7' procurement list and their alternative drugs that have not yet been covered by the policy. '4+7' List drugs were divided into bid-winning and non-winning products according to the bidding results. Included drugs were sorted into original and generic products. Difference-in-difference method was employed to estimate the net effect of policy impact. RESULTS: After policy intervention, the DDDs (defined daily doses) of '4+7' List original drugs significantly reduced (ß=-39.10, p<0.001), while generic drugs increased (ß=40.43, p<0.01). 17.08% of the original drugs in DDDs were substituted by generic drugs. Prominent reduction was observed in the monthly expenditure of '4+7' List drugs (¥726.40 million) and overall policy-related drugs (¥654.47 million). The defined daily drug cost (DDDc) of bid-winning original and generic drugs, as well as non-winning original drugs, decreased by 44.44%, 79.00% and 15.10% (all p<0.01), while the DDDc of non-winning generic drugs increased by 64.81% (p<0.001). The use proportion of higher-quality drugs raised prominently from 39.66% to 91.93%. CONCLUSIONS: '4+7' policy is conducive to generic substitution, drug price reduction and pharmaceutical cost-containment in China. The overall quality level of drug use of the Chinese population increased after policy intervention, especially in primary healthcare settings. However, the increased DDDc of non-winning generic drugs and alternative drugs should draw the importance of further policy monitoring.

The Effects of the National Centralized Drug Purchasing Pilot Program on Nucleos(t)ide Analogs in Shenzhen City: An Interrupted Time Series Analysis.

Objectives: To assess the effects of the National Centralized Drug Purchasing Pilot Program on nucleos(t)ide analogs (NAs) in Shenzhen city. Methods: Drugs procurement records in medical institutions were analyzed covering the period from January 2018 to December 2019. An interrupted time series (ITS) analysis was used to evaluate the impact of the "4+7" pilot policy on NAs in Shenzhen city. The outcome measures were usage volume, expenditures, daily cost, and distribution structure of NAs. Findings: After the introduction of the "4+7" pilot policy, the defined daily doses (DDDs) of NA drugs increased by 76.48%, the expenditures and defined daily dose cost (DDDc) of NAs decreased by 45.43 and 69.08%, respectively. The proportion of winning products in Entecavir and Tenofovir Fumarate DDDs was increased by 64.21 and 19.20%, respectively. The post-intervention period witnessed a significant increase in the regression level for NAs DDDs (level coefficient: ß2 = 631.87, p < 0.05). The expenditures (trend coefficient: ß3 = 392.24, p < 0.05) and DDDc (level coefficient: ß2 = -6.17, p < 0.001; trend coefficient: ß3 = -0.21, p < 0.05) of NAs showed decreasing trend in the post-intervention period. The expenditures of original products and generic products both showed a decreasing trend in the post-intervention period (trend coefficient: ß3 = -372.78, p < 0.05, trend coefficient: ß3 = -130.78, p < 0.05, respectively). The DDDc of original products in the policy-related varieties was a significant decrease in the regression slope and level (level coefficient: ß2 = -2.18, p < 0.05; trend coefficient: ß3 = -0.32, p < 0.01). Conclusion: After the implementation of the"4+7" policy, the DDDc of NAs decreased, the accessibility of policy-related drugs was improved, and the usage of generic medicine was promoted.

Anti­oxidative and anti­apoptotic neuroprotective effects of Azadirachta indica in Parkinson­induced functional damage.

Azadirachta indica has previously been demonstrated to act as a multi­functional medicinal plant for >2,000 years in India, and its neighboring countries. Currently, it is considered a natural resource with great value used in industrial product development and as a medicine for various types of diseases. The present study investigated the neuroprotective effects of Azadirachta indica which improved functional recovery in the 6­hydroxydopamine induced rat Parkinson's disease (PD) model. Catalase, glutathione­peroxidase, tumor necrosis factor­α, interleukin (IL)­1ß, IL­6, nuclear factor (NF)­κB p65, inducible nitric oxide synthase (iNOS) and AChE activity levels were analyzed via ELISA. Western blotting was used to analyze B cell lymphoma­2 associated X protein (Bax), cytochrome c and p53 protein expression. Treatment with Azadirachta indica significantly decreased the PD­induced rotational behavior in rats. PD­induced catalase, glutathione­peroxidase, iNOS activity and iNOS protein expression were significantly suppressed by treatment with Azadirachta indica. Inflammatory factors, acetylcholinesterase activity and cyclo­oxygenase­2 protein expression levels were additionally significantly suppressed by treatment with Azadirachta indica. The protein expression levels of Bax, cytochrome c and p53 were decreased and caspase­3 and caspase­9 activities diminished, with treatment with Azadirachta indica. Therefore, Azadirachta indica was demonstrated to exhibit neuroprotective antioxidative and anti­apoptotic effects in Parkinson's disease.