Oral Bacterial Lysate OM-85: Advances in Pharmacology and Therapeutics.

Background: Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1 helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Methods: Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. Results: New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient's characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification). Conclusion: OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.

A systematic review of economic evaluations of orphan medicines for the management of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a rare inherited autosomal recessive progressive disease of a varying phenotype, with varying clinical symptoms, and as a result the patients suffering from it require multiple types of care. It was deemed useful to conduct a systematic literature review on the pharmacoeconomic evaluations of all currently registered disease-modifying therapies in order to inform policy and highlight research gaps. Pharmacoeconomic analyses written in English and published after 2016 were considered for inclusion. PubMed/Medline, Global Health and Embase were systematically and separately searched between 16 October and 23 October 2023. Hand-searching was also conducted on PubMed based on reference lists of published literature. After the exclusion criteria were applied, 14 studies were included. BMJ checklist was used for quality assessment and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to assess the quality of reporting of all included studies. Data extraction was performed manually. Regarding evidence synthesis, data were heterogeneous and are thus presented based on comparison. This study confirms the need for pharmacoeconomic analyses (cost-effectiveness or cost-utility) also in cases when the cost of treatment is very high and the incremental cost-effectiveness ratio values exceed the usual, acceptable values for standard therapy. Specific willingness to pay thresholds for orphan medicines are of the utmost importance, to allow patients with SMA to have access to safe and effective treatments. With such economic evaluations, it is possible to compare the value of medications with the same indication, but it should be emphasized that in the interpretation of data and in making decisions about the use of medicines, the impact of new knowledge should be considered.

[Pharmacoeconomic evaluation of Shaoma Zhijing Granules in treatment of tic disorders in children].

This study conducted a pharmacoeconomic evaluation of Shaoma Zhijing Granules in the treatment of tic disorder(TD) in children. Firstly, from the perspective of the healthcare system, cost-effectiveness analysis was used to evaluate the economic efficiency of Shaoma Zhijing Granules compared with Changma Xifeng Tablets and Jiuwei Xifeng Granules in the treatment of TD in children. Then, through network Meta-analysis, the overall effectiveness of different regimens was calculated, combined with the total cost of the regimens, to calculate the incremental cost-effectiveness ratio(ICER). Finally, sensitivity analysis was performed to verify the stability of the study results and the credibility of the conclusions. This study included 17 articles, including 9 articles on Chinese patent medicines(3 on Shaoma Zhijing Granules, 2 on Jiuwei Xifeng Granules, and 4 on Changma Xifeng Tablets), for the treatment of TD in children, and 8 articles on Chinese patent medicines combined with conventional western medicines(3 on Shaoma Zhijing Granules, 2 on Jiuwei Xifeng Granules, and 3 on Changma Xifeng Tablets). In the Chinese patent medicine group, the total cost of Shaoma Zhijing Granules for treating TD was CNY 4 410.00, with clinical total effective rate of 77.53%; the total cost of Jiuwei Xifeng Granules for treating TD was CNY 5 192.70, with clinical total effective rate of 82.13%. The ICER of Jiuwei Xifeng Granules vs Shaoma Zhijing Granules was 169.95, higher than the willingness-to-pay(WTP, cost of increasing efficiency by 1% is CNY 85.70). Therefore, Jiuwei Xifeng Granules did not have a cost-effectiveness advantage over Shaoma Zhijing Granules. The total cost of Changma Xifeng Tablets for treating TD was CNY 1 282.50, with clinical total effective rate of 80.60%. The total cost of Changma Xifeng Tablets was lower and clinical total effective rate was higher than that of Shaoma Zhijing Granules. Overall, Shaoma Zhijing Granules did not have a cost-effectiveness advantage. In the Chinese patent medicine combined with conventional western medicine group, the total cost of Shaoma Zhijing Granules for treating TD + conventional western medicines was CNY 6 768.52/6 778.48, with clinical total effective rate of 96.18%. The total cost of Jiuwei Xifeng Granules + conventional western medicines for treating TD was CNY 6 522.56, with clinical total effective rate of 88.30%. The ICER of Shaoma Zhijing Granules + conventional western medicines vs Jiuwei Xifeng Granules + conventional western medicines was 31.20, lower than WTP. Therefore, Shaoma Zhijing Granules + conventional western medicines had a cost-effectiveness advantage over Jiuwei Xifeng Granules + conventional western medicines. The total cost of Changma Xifeng Tablets + conventional western medicines for treating TD was CNY 1 706.12, with clinical total effective rate of 95.39%. The ICER of Shaoma Zhijing Granules + conventional western medicines vs Changma Xifeng Tablets + conventional western medicines was 6 334.06, higher than WTP. Therefore, although Shaoma Zhijing Granules + conventional western medicines had higher clinical total effective rate compared with Changma Xifeng Tablets + conventional western medicines, it did not have a cost-effectiveness advantage. Overall, for different medication regimens(Chinese patent medicines monotherapy or in combination with conventional western medicines), Shaoma Zhijing Granules and Jiuwei Xifeng Granules both had a cost-effectiveness advantage, but compared with Changma Xifeng Tablets, neither had a cost-effectiveness advantage. For Chinese patent medicines in combination with conventional western medicines, clinical total effective rate of Shaoma Zhijing Granules in combination with conventional western medicines for the treatment of TD in children was the highest.

A Markov model-based cost-effectiveness analysis comparing zanubrutinib to ibrutinib for treating relapsed and refractory chronic lymphocytic leukemia.

OBJECTIVE: This article examined the cost-effectiveness of zanubrutinib and ibrutinib for managing relapsed and refractory chronic lymphocytic leukemia from the viewpoint of payers in China and the US. METHODS: Markov models were employed to conduct comparisons. Baseline characteristics and clinical data were extracted from the ALPINE study. The cost-effectiveness outcome indicators encompassed cost, quality-adjusted life years, and the incremental cost-effectiveness ratio. RESULTS: The Markov model analysis revealed that the zanubrutinib group incurred an incremental cost per patient of $-24,586.53 compared to the ibrutinib group. The zanubrutinib group exhibited an incremental utility per capita of 0.28 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio of $-88,068.16 per quality-adjusted life year, which is lower than the payment threshold in China. The willingness-to-pay value in China for 2022 was three times the country's gross domestic product per capita. In the US, patients in the zanubrutinib group experienced per capita incremental costs of $-79,421.56, per capita incremental utility of 0.28 quality-adjusted life years, and an incremental cost-effectiveness ratio of $-284,485.45 per quality-adjusted life year. CONCLUSION: For Chinese payers, zanubrutinib exhibited superior cost-effectiveness compared to ibrutinib. Zanubrutinib proved to be a more affordable option for US payers when considering the payment threshold.

Cost-effectiveness thresholds or decision-making threshold: a novel perspective.

The use of multiple cost-effectiveness thresholds in pharmacoeconomic evaluation is a hotly debated topic in the international academic community. This study analyzed and discussed thresholds in the context of pharmacoeconomic evaluation and reimbursement decision-making. We suggest that the thresholds inferred from reimbursement decisions should be distinguished from cost-effectiveness threshold in pharmacoeconomic evaluation. Pharmacoeconomic evaluations should adopt a fixed threshold, which should not vary with the subjects evaluated. This would help avoid the invitation of numerous cost-effectiveness thresholds for a specific drug, an exceptional disease, a type of innovation, or a certain level of malignancy, which misleads economic evaluation adopting restless changing standards and making pharmacoeconomic evaluation and decision-making more complex and contradictory.

Pharmacoeconomic evaluation of 2 kinds of inhalation schemes of budesonide for mild asthma / 中国药房

OBJECTIVE To evaluate the cost-utility of as-needed inhaled budesonide/formoterol versus budesonide maintenance therapy combined with as-needed inhaled terbutaline （hereinafter referred to as budesonide maintenance therapy） in patients with mild asthma from the perspective of the Chinese health service system. METHODS A Markov model of mild asthma was established based on an international multicenter randomized controlled clinical study （SYGMA 2 study）； the model cycle was one week， and the model had a whole horizon of 60 years. The cost only included direct medical cost， and utility value was derived from the data of EuroQol 5-Dimension 5-Level in the SYGMA 2 study and published literature. The total cost and total output of the above two inhalation therapies for patients with mild asthma were calculated， with discount rate of 5%. The stability of the model was evaluated by sensitivity analysis. RESULTS The total cost of as-needed inhaled budesonide/formoterol and budesonide maintenance therapy were 25 884 yuan and 45 822 yuan， respectively， and the effectiveness were 30.51 quality- adjusted life years （QALYs） and 30.50 QALYs， respectively. The former scheme was an absolute advantage. One-way sensitivity analyses showed that the price of drug （terbutaline and budesonide/formoterol） and average number of inhalations per day were the main influencing parameters， but they had little influence on the results of basic analysis. Probabilistic sensitivity analysis showed that the probability of as-needed budesonide/formoterol being cost-effective was 100%. CONCLUSIONS Compared with budesonide maintenance therapy， as-needed inhalation of budesonide/formoterol in mild asthma patients is more cost-effective.

Pharmacoeconomic evaluation of clopidogrel versus aspirin for secondary prevention of ischemic stroke / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

Pharmacoeconomic evaluations of CDK4/6 inhibitors plus endocrine therapy for advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) breast cancer: a systematic review.

Background: Hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) breast cancer is the most common molecular subtype of breast cancer in many countries, and endocrine therapy remains a mainstay in its treatment. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of targeted agents administered orally that are recommended being used in combination with endocrine therapy as first and second line treatments for advanced HR+/HER2- breast cancer. However, their high prices largely hinder using these drugs in real world settings. To offer a new basis for future research, we investigated the cost-effectiveness of combinations of CDK4/6 inhibitors with endocrine therapy in the treatment of advanced HR+/HER2- breast cancer. Methods: We systematically searched several frequently used databases and identified economic evaluations published from February 2015 to April 2021. The systematic review was performed after retrieving the literatures and extracting data based on inclusion and exclusion criteria. The quality of each selected economic evaluation was assessed by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Results: The literature search yielded 161 articles, among which fourteen studies (15 articles) with CHEER scores ranging from 58.33% to 87.50% entered the final analysis. Markov models were used in most studies. Based on the currently available data, CDK4/6 inhibitors plus endocrine therapy were less cost-effective in first- or second-line treatment of patients with HR+/HER2- advanced breast cancer. However, ribociclib plus letrozole was more cost-effective than palbociclib plus letrozole in the first-line treatment of postmenopausal women. The economic impacts of CDK4/6 inhibitors plus endocrine therapy in non-postmenopausal patients or second-line therapy cannot be fully evaluated due to the limited number of studies. The three most common factors affecting economic outcomes were the prices of CDK4/6 inhibitors, hazard ratios for progression-free survival and overall survival, and health status utility values. Discussion: CDK4/6 inhibitors plus endocrine therapy have shown significantly improved efficacy outcomes in HR+/HER2- metastatic breast cancer (mBC)/advancer breast cancer (ABC) first-line and second-line treatment for endocrine-sensitive and endocrine-resistant populations, while more potential fields including neoadjuvant and adjuvant settings are being identified to benefit a wider range of breast cancer patients. Meanwhile, risk of severe adverse events that more likely to happen in patients treated with CDK4/6 inhibitors can lead to reduced life quality and higher medical costs patients need to afford. The adverse drug reaction related cost in several economic burden studies were explored to be primarily driven by hospitalizations and outpatient, and assessment of cost associated with CDK4/6 inhibitors adverse events is worth further developing. Drug wastage costs were found higher in palbociclib regimen than ribociclib regimen due to different dosing patterns. Moreover, current economic evaluations showed that ribociclib plus letrozole had better economic benefits than palbociclib plus letrozole for first-line treatment of postmenopausal women with HR+/HER2- ABC.

A pharmacoeconomic evaluation of the pharmacotherapeutic options for painful diabetic neuropathy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is a high incidence and severe complication of diabetes mellitus, significantly compromising patients' quality of life and causing tremendous economic burden. Considering drug costs becomes part of treatment decisions, with the growing choice of monotherapy or combination treatment strategies for PDN treatment. AREAS COVERED: This systematic review aims to identify the cost-effectiveness of pharmacotherapies in PDN, summarize key findings, and assess the quality of studies to inform healthcare resource allocation decisions and future research. Economic evaluations were identified by searching PubMed, Web of Science, Scopus and health technology assessment (HTA) databases, as well as screening reference lists of previously identified studies. Relevant data was extracted, and the CHEERS checklist was used to assess the quality of the studies. EXPERT OPINION: Collectively, the findings indicate that more pharmacoeconomics research is urgently needed to directly compare high-quality research for PDN combination medication/sequential treatment, and which is performed from a societal perspective. Simultaneously, to strengthen the reliability of the analysis, metrics such as adherence, incidence of adverse drug reactions, and pain levels utility value should be examined to verify the robustness of the basic results.

Pharmacoeconomic evaluation of loratinib in the first-line treatment of anaplastic lymphoma kinase-positive advanced non-small cell lung cancer / 中国药房

OBJECTIVE To eva luate the economy of loratinib versus crizo tinib in the first-line treatment of anaplastic lymphoma kinase （ALK）-positive advanced non-small cell lung cancer （NSCLC）from the perspective of China ’s health system ， and to provide reference for the product pricing and related medical decisions of the drug in other regions of China except for Hong Kong. METHODS Markov model and partition survival model both constructed based on the CROWN data （the simulation time limit was 10 years and the cycle period was 4 weeks）；the quality adjusted life year （QALY）was used as the outcome index to calculate the incremental cost-effectiveness ratio （ICER）. One-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the results. RESULTS The basic analysis results based on Markov model showed that compared with crizotinib group ，the per capita cost of loratinib group increased by 17 867 588.63 yuan，the per capita utility increased by 1.76 QALYs，and the ICER was 10 152 038.99 yuan/QALY. The basic analysis results based on the partition survival model showed that compared with the crizotinib group ，the Δ 基金项目：江苏省博士后科研资助计划项目（No.2021K496C）； per capita cost of loratinib group increased by 18 009 592.54 2020年度高校哲学社会科学研究一般项目（No.2020SJA0070） yuan，the per capita utility increased by 1.74 QALYs，and the ＊硕士研究生 。研究方向 ：药物经济学 、卫生经济与政策 。 E-mail：sunlei_cpu@163.com ICER was 10 350 340.54 yuan/QALY. The results of one-way # 通信作者：教授，博士生导师。研究方向：药物经济学、卫生经 sensitivity analysis of the two models both showed that 济与政策。E-mail：ma86128@sina.com progression-free survival （PFS）state utility v alue，progression- ·1102· China Pharmacy 2022Vol. 33 No. 9 中国药房 2022年第33卷第9期 disease（PD）state utility value and loratinib cost had great influence on the results. The results of probability sensitivity analysis showed that when 1-3 times of China ’s per capita GDP in 2020 was taken as the willingness to pay threshold ，the probability of loratinib being economical was 0. The recommended unit price of loratinib per 100 mg was 657.10-815.60 yuan. CONCLUSIONS For patients with ALK-positive advanced NSCLC ，loratinib is more effective than crizotinib in the first-line treatment ，but it is not economical under the current price ；reasonably lowering the price of loratinib can increase the probability of its economy.

A systematic review of pharmacoeconomic evaluations on oral diarylquinoline-based treatment for drug-resistant tuberculosis: from high to low burden countries.

Introduction: There is a rising global interest in the pharmacoeconomic evaluations of bedaquiline (BDQ), a novel oral diarylquinoline, for treatment of drug-resistant tuberculosis (DR-TB).Areas covered: This article systematically reviewed publications retrieved from Medline, American Psychological Association-Psychology information, Web of Science, Embase, Scopus, Science direct, Center for Reviews and Dissemination, and CINAHL Complete during 2010-2020 on pharmacoeconomic studies on BDQ for DR-TB treatment. Ten Markov model-based cost-effectiveness analyses identified were conducted in high (n = 4), intermediate (n = 2), and low (n = 4) TB burden countries.Expert opinion: The paucity of model-based health economic analyses on BDQ-containing regimens for DR-TB indicated that further pharmacoeconomic research of BDQ-based regimens, on the aspects of duration of BDQ treatment, types of DR-TB indicated, and settings of regions and health-systems, is highly warranted to inform global cost-effective use of BDQ-based regimens for DR-TB treatment.

Cost-effectiveness analysis of 5% lidocaine-medicated plaster compared with pregabalin for the treatment of post-herpetic neuralgia in China.

BACKGROUND: Post-herpetic neuralgia (PHN) is the most common complication of herpes zoster and is defined as pain that lasts for one month or more after the outbreak itself heals. While the annual incidence of herpes zoster is approximately 3-5%, 9-34% of these patients will develop PHN. Approximately 30-50% of these cases last for more than a year but some cases can persist for 10 years or more. To date, the economic burden of PHN in China has not been studied. The first-line topical therapy for PHN is application of lidocaine-medicated plasters (LMPs) which have shown good efficacy and tolerability. Furthermore, LMPs were added to China's National Health Insurance List in 2019, thereby significantly relieving the financial burden on patients. A cost-effectiveness analysis was performed on LMPs compared with pregabalin in the treatment of PHN to provide a reference for the basis for clinical treatments and health decisions in patients with PHN. METHODS: A Markov model was built according to the PHN disease characteristics. The efficacy data were extracted from a randomized controlled trial conducted in China, and the transition probability, utility value, and medical cost of each state in the model were collected through a systematic review of the literature and public databases. The outcome measure was cost per quality-adjusted life year (QALY) gained. The incremental cost-effectiveness ratios (ICERs) were calculated. Sensitivity analysis was conducted to confirm the robustness of the model. RESULTS: In the base case analysis, treatment for a 6-month period with pregabalin and lidocaine plasters led to a mean QALY gain of 0.34012 and 0.42543, respectively, and mean incremental costs of 5,720 Chinese Yuan (CNY) and 3690 CNY, respectively. The ICER of treatment with 5% lidocaine plaster was negative, indicating that lidocaine plasters had absolute advantage. Monte Carlo simulation resulted in an estimate of 90% probability that the 5% lidocaine plaster treatment was cost-effective. CONCLUSIONS: Within the Chinese medical and health system, LMPs can reduce the economic burden of patients with PHN. LMPs are more cost-effective and more efficient in absolute terms compared to the first-line treatment systemic drug pregabalin in the treatment of PHN.

Economic Evaluation of Dexamethasone Combined with Rituximab for the First-line Treatment of Chronic Primary Immune Thrombocytopenia in Adults / 中国药房

OBJECTIVE：To evaluate the economy performance of dexamethasone （DXM）combined with rituximab （RTX） for the first-line treatment of chronic primary immune thrombocytopenia （ITP）in adults. METHODS ：From the perspective of China ’s medical and health system ，Markov model for eight states was constructed with a period of 4 weeks and a time limit of 20 years， using DXM regimen as control. The cost-utility of DXM+RTX regimen for the treatment of chronic ITP in adults were evaluated. The parameters of clinical efficacy and utility value were derived from own published literature ；cost parameters were from the MENET website and the official websites of local health committees and medical insurance bureaus ；one-way sensitivity analysis ， probability sensitivity analysis and scenario analysis were performed to observe the uncertainty of model and data source. RESULTS：The average cost of DXM+RTX regimen was 51 064 dollars and that of DXM regimen was 50 455 dollars. Compared with DXM regimen ，DXM+RTX regimen yielded an additional 0.14 QALYs for each patient ；the incremental cost-effectiveness ratio（ICER）was 4 356 dollars/QALY，and was lower than the willingness-to-pay threshold of China ’s per capita gross domestic product（GDP）in 2020. In the one-way sensitivity analysis ，the cost of drugs was the main driver in the model. Probability sensitivity analysis demonstrated that DXM+RTX regimen had 57.5％-61.0％ probability of being cost-effective at a willingness- to-pay threshold of 1-3 times per capita GDP in 2020. The results of scenario analysis showed that DXM+RTX regimen would have obvious long-term benefits ，and the utility value had little impact on the conclusion. CONCLUSIONS ：DXM + RTX is more economical than DXM in the treatment of chronic ITP in adults ，but the results have the uncertainty.

The current state of patient access to new drugs in South Korea under the positive list system: evaluation of the changes since the new review pathways.

Objective: This study aims to provide an up-to-date analysis of the current state of patient access to new drugs in South Korea, focusing on the effect of new review pathways for reimbursement. Methods: We analyzed patients' access to new drugs, listing rate and lead time until listing from marketing authorization. New pathways were defined as 'price negotiation waiver,' 'risk-sharing agreements,' and 'pharmacoeconomic evaluation exemption.' Results: The listing rate for drugs increased after the introduction of the new pathways (93.7% vs. 77.9%, p < 0.001). Before the new pathways, the median lead time for listing was 21.0 months (95% CI: 16.9-25.0), while afterward it was shortened to 10.9 months (95% CI: 10.2-11.7) (p < 0.001). Conclusion: Although it has strengthened national health insurance coverage by positively impacting the rate and lead time, the lead time for the oncology and orphan drugs is substantially longer as compared to other drugs. Expanding the eligibility criteria to include non-life-threatening but rare or intractable diseases, and resolving the system's operational issues are still necessary.

Cost-effectiveness analyses of breast cancer medications use in developing countries: a systematic review.

BACKGROUND: Pharmacoeconomic evaluation is important for breast-cancer medications due to their high costs. To our knowledge, no systematic literature reviews of pharmacoeconomic studies for breast-cancer medication use are present in developing-countries. OBJECTIVES: To systematically review the existing cost-effectiveness evaluations of breast-cancer medication in developing-countries. METHODOLOGY: A systematic literature search was performed in PubMed, EMBASE, SCOPUS, and EconLit. Two researchers determined the final articles, extracted data, and evaluated their quality using the Quality of Health-Economic Studies (QHES) tool. The interclass-correlation-coefficient (ICC) was calculated to assess interrater-reliability. Data were summarized descriptively. RESULTS: Fourteen pharmacoeconomic studies published from 2009 to 2019 were included. Thirteen used patient-life-years as their effectiveness unit, of which 10 used quality-adjusted life-years. Most of the evaluations focused on trastuzumab as a single agent or on regimens containing trastuzumab (n = 10). The conclusion of cost-effectiveness analysis varied among the studies. All the studies were of high quality (QHES score >75). Interrater reliability between the two reviewers was high (ICC = 0.76). CONCLUSION: In many studies included in the review, the use of breast-cancer drugs in developing countries was not cost-effective. Yet, more pharmacoeconomic evaluations for the use of recently approved agents in different disease stages are needed in developing countries.

Clinical and pharmacoeconomic evaluation of antifungal prophylaxis with continuous micafungin in patients undergoing allogeneic stem cell transplantation: A six-year cohort analysis.

BACKGROUND: Patients undergoing allogeneic stem cell transplantation (aSCT) are at high risk to develop an invasive fungal disease (IFD). Optimisation of antifungal prophylaxis strategies may improve patient outcomes and reduce treatment costs. OBJECTIVES: To analyse the clinical and economical impact of using continuous micafungin as antifungal prophylaxis. PATIENTS/METHODS: We performed a single-centre evaluation comparing patients who received either oral posaconazole with micafungin as intravenous bridging as required (POS-MIC) to patients who received only micafungin (MIC) as antifungal prophylaxis after aSCT. Epidemiological, clinical and direct treatment cost data extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut) were analysed. RESULTS: Three hundred and thirteen patients (97 and 216 patients in the POS-MIC and MIC groups, respectively) were included into the analysis. In the POS-MIC and MIC groups, median overall length of stay was 42 days (IQR: 35-52 days) vs 40 days (IQR: 35-49 days; p = .296), resulting in median overall costs of €42,964 (IQR: €35,040-€56,348) vs €43,291 (IQR: €37,281 vs €51,848; p = .993), respectively. Probable/proven IFD in the POS-MIC and MIC groups occurred in 5 patients (5%) vs 3 patients (1%; p = .051), respectively. The Kaplan-Meier analysis showed improved outcome of patients in the MIC group at day 100 (p = .037) and day 365 (p < .001) following aSCT. CONCLUSIONS: Our study results demonstrate improved outcomes in the MIC group compared with the POS-MIC group, which can in part be explained by a tendency towards less probable/proven IFD. Higher drug acquisition costs of micafungin did not translate into higher overall costs.

Pharmacoeconomic Evaluation of Perospirone in the Treatment of Schizophrenia ：A Study Based on Major Adverse Events / 中国药房

OBJECTIVE：To evaluate the economy of pe rospirone in the treatment of schizophrenia ，to provide guidance for clinically proper use of medications more cost-effectively ，and related health decision-making . METHODS ：A short-term decision tree model was constructed from the perspective of medical insurance payer to calculate the cost and health outcomes of different treatment plans considering major adverse events including extrapyramidal reaction ，weight gain ，diabetes，hyperlipidemia. The cost-utility of perospirone were compared with quetiapine ，aripiprazole and olanzapine respectively ，using QALYs as the measure of health outcomes ，3 times GDP per capita as the willingness-to-pay threshold ；probability sensitivity analysis was performed. RESULTS：The results of base-case analysis showed that the cost of perospirone （6 688.25 yuan）was lower than those of quetiapine （9 887.45 yuan），aripiprazole（13 284.65 yuan）and olanzapine （15 332.80 yuan）. The utility of perospirone （0.79 QALYs）was better than those of quetiapine （0.76 QALYs），aripiprazole（0.77 QALYs）and olanzapine （0.75 QALYs）. Compared with quetiapine ， aripiprazole and olanzapine ，peropirone had lower cost and higher health outcome ，which indicated that strong dominance favors perospirone over the other 3 drugs. The results of sensitivity analysis were consistent with those of base-case analysis. CONCLUSIONS：Perospirone has economic advantages in treating schizophrenia patients compared to other commonly used atypical antipsychotic drugs.

Literature Study on Pharmacoeconomic Evaluation of Aspirin for Cardiovascular Disease Prevention / 中国药房

OBJECTIVE：To review the method and results of pharmacoeconomic evaluation of aspirin for cardiovascular disease prevention ，and to provide reference for economic evaluation of aspirin and clinical medication decision. METHODS ： Using“cardiovascular disease ”“cost-effectiveness”“cost-utility”“cost-benefit”“cost effectiveness ”“cost utility ”as the Chinese search terms ，using“cost-effectiveness”“cost-utility”“cost-benefit”“economic analysis ”“pharmacoeconomics”as English search terms，relevant literatures about pharmacoeconomic evaluation of aspirin for cardiovascular disease prevention published during January 1，2000 to January 17，2021 were retrieved from CNKI ，Wanfang database ，VIP，PubMed，Web of Science ，the Cochrane Library. After screening literatures according to inclusion and exclusion criteria ，extracting relevant data ，the quality of included literatures was evaluated with CHEERS scale. The method and results of pharmacoeconomic evaluation of aspirin in the prevention of cardiovascular diseases were analyzed statistically in terms of basic information ，literature quality ，model structure and elements ，health status and utility value ，cost items and sources ，health output ，economic evaluation and sensitivity analysis. RESULTS & CONCLUSIONS ：Nine literatures were included ，and the total coincidence rates of the literatures were all above 80.00％. The pharmacoeconomic evaluation of aspirin in the prevention of cardiovascular disease mainly adopted Markov model ， and the model structure was relatively mature. The cost mainly considered the direct cost ，and the data mainly came from the medical insurance database ；utility was calculated according to the utility value of health state ，which mostly came from the existing literatures. The sensitivity analysis adopted deterministic sensitivity analysis and probabilistic sensitivity analysis ，and the main influential factor was cost. It was economical to use aspirin for cardiovascular disease prevention in most cases ，and aspirin was more economical for primary prevention of cardiovascular disease. It is suggested that domestic scholars can refer to China ’s pharmacoeconomic guidelines to carry out relvant pharmacoeconomic evaluation research more standardized.

Pharmacoeconomic Evaluation of Cancer Biosimilars Worldwide: A Systematic Review.

Background and Purpose: The availability of oncology biosimilars is deemed as a fundamental strategy to achieve sustainable health care. However, there is scarce systematic evidence on economic effectiveness of cancer biosimilars. We aimed to synthesize evidence from pharmacoeconomic evaluation of oncology biosimilars globally, provide essential data and methodological reference for involved stakeholders. Materials and Methods: This systematic review was conducted in PubMed, embase, the Cochrane library, CRD, ISPOR and NICE utill December 31, 2019. Information on basic characteristics, evaluation methodology and results were extracted. Quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards Checklist. Results: For 17 studies identified (13 from Europe and four from United States), the overall quality was generally acceptable. A total of seven biological molecules involved with filgrastim, EPOETIN α, and trastuzumab leading the three. The mostly common evaluation perspective was payer, but the time horizon varied greatly. There were ten studies which adopted cost minimization analysis to evaluate efficiency while seven studies adopted budget impact analysis to address affordability, with cost ratio and cost saving being its corresponding primary endpoint. Although the comparability of included studies was limited and specific results were largely affected by uptake and price discount rates of the oncology biosimilar, the comprehensive results consistently favored its promotion. Conclusion: Globally, the economic evaluation of cancer biosimilars is in its initial phase. However, limited evidence from developed countries consistently supported both cost-effectiveness of efficiency and affordability of oncology biosimilars, while they were largely affected by uptake and price discount rate.

Bibliometric Study on Health Utility Value Obtained by Mapping Method in Pharmacoeconomic Evaluation / 中国药房

OBJECTIVE：To know about the research status of health utility value obtained by mapping method in pharmacoeconomic evaluation ，and to provide reference for bibliometric study in pharmacoeconomic evaluation . METHODS ： Using“Mapping method ”“Health utility value ”“Cost-utility”“Utility point system ”as Chinese and English keywords ，retrieved from CNKI ，Wanfang database ，PubMed，Medline，Ebsco，Ovid and Wiley database ，empirical journal documents published from the inception to Dec. 31st，2018 about using mapping method to obtain health utility value were collected. The bibliometrics was used to statistically analyze basic information of included literature ，the construction and test of the model ，the type of the best model and so on. RESULTS ：The 124 included documents were all published in English journal. In the construction and testing of the mapping model ，the most frequently used econometric methods ，performance evaluation indicators and model testing methods were ordinary least squares （OLS），mean absolute error （MAE）and residual normality test ，application frequency of which were 97 times（31.60％），89 times（24.93％）and 62 times（21.09％）. There are 117 articles that define the best mapping model ，of which 101 articles（86.32％）have the best direct mapping effect. Most of the non-utility measurement scales adopted specific scales （92 articles，77.97％），and a few literatures adopted the universal scale （26 articles，22.03％）. The most utility measurement scales were 3-level European 5-dimensional health scale （79 articles，66.95％）. CONCLUSIONS ：The domestic empirical researches that use the mapping method to obtain health utility values need to be developed yet. A series of mapping models successfully developed by foreign scholars not only provide the feasibility of using non-utility measurement scales for cost-utility analysis ，but also provide more ideas for China to choose the corresponding econometric methods ，evaluation indicators and mapping methods in the empirical research of the mapping method in the future.