BACKGROUND: The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China.
METHODS: We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region.
RESULTS: During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients\' payment capability level, but an increasing trend (11.94%-18.42) under rural patients\' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend.
CONCLUSIONS: This study demonstrates that access to drugs for urban cancer patients has improved. However, patients\' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation\'s health insurance funds.

Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer medicines and explore factors influencing the reimbursement process in seven high-income European countries.
We carried out a retrospective case study of anticancer medicines with European Union Market Access (EU-MA) and a positive Committee for Medicinal Products for Human Use opinion from 2016 until 2021 with subsequent national reimbursement approval (NRA). The National Health Technology Assessment (HTA) and reimbursement websites of Germany, France, UK, the Netherlands, Belgium, Norway and Switzerland were used to identify TTR, defined as time from EU-MA to NRA. Additionally, we investigated medication-, country-, indication- and pharma-related factors potentially influencing TTR.
Thirty-five medicines were identified for which TTR ranged from -81 days to 2320 days (median 407 days). At data cut-off, 16 (46%) were reimbursed in all seven countries. Overall, the shortest TTR was in Germany (median 3 days, all medicines reimbursed <5 days). The time limit for reimbursement of 180 days stated by the Council of European Communities after the EU-MA (EU Transparency Directive) was met for 100% of included medicines in Germany, 51% in France, 29% in the UK and the Netherlands, 14% in Switzerland, 6% in Norway and 3% in Belgium. The TTR was significantly different between countries (P < 0.001). In multivariate analysis, factors associated with shorter TTR were higher gross domestic product (GDP), absence of a pre-assessment procedure and submission by a big pharmaceutical company.
TTR of anticancer medicines varies significantly between seven high-income European countries and leads to inequality in access. Among explored medication-, country-, indication- and pharma-related factors we found that a high GDP, the absence of a pre-assessment procedure and submission by big pharmaceutical companies were associated with shorter TTR.

Fluoroquinolones have been studied for more than half a century. Since the 1960s, four generations of these synthetic antibiotics have been created and successfully introduced into clinical practice. However, they are still of interest for medicinal chemistry due to the wide possibilities for chemical modification, with subsequent useful changes in the pharmacokinetics and pharmacodynamics of the initial molecules. This review summarizes the chemical and pharmacological results of fluoroquinolones hybridization by introducing different heterocyclic moieties into position 3 of the core system. It analyses the synthetic procedures and approaches to the formation of heterocycles from the fluoroquinolone carboxyl group and reveals the most convenient ways for such procedures. Further, the results of biological activity investigations for the obtained hybrid pharmacophore systems are presented. The latter revealed numerous promising molecules that can be further studied to overcome the problem of resistance to antibiotics, to find novel anticancer agents and more.

OBJECTIVE: Cancer is the second leading cause of death in the world after cardiovascular disease. The present study aimed to investigate the affordability and physical access to chemotherapy drugs among patients with one of the three common cancers of the breast, stomach, and colon in the city of Mashhad, Iran, in 2021.
METHODS: This was a descriptive cross-sectional study. Twenty drug stores including two public and 18 privates in Mashhad were evaluated. Data was collected by consistent stay in the drug stores or pharmacies. For each oncology medicine, selling price, lowest general price, and availability were investigated. Three approaches have been experimented to calculate the affordability of anticancer medicines in this study.
RESULTS: Out of 28 studied medicines from public and private drug stores, 15 (53.5%) received very low, 8 (28.5%) relatively high, and 2 (7%) high access scores. The generic docetaxel brand\'s ultra-drug and trastuzumab (AryoTrust) were the most available drugs, but the doxorubicin (Ebewe), oxaliplatin (Mylan), and trastuzumab (Herceptin) were not available to the individuals with cancer. Also, the first approach (based on income decile) indicated that insured patients from all income deciles were able to pay the costs of the lowest price drugs of the DCF drug regimen, and if the patients were insured and belonged to the ninth income decile, they had the financial ability to buy drugs at the lowest price of the FLO drug regimen.
CONCLUSIONS: Unaffordability of cancer medicines can lead to treatment abandonment and increase inequality in access to healthcare services. Therefore, this requires immediate attention of policy makers to be planned in order to ensure to reducing the costs of medicines for patients and increasing patient access to anticancer medicines.

There is an alarming delay in Europe for anticancer medicines becoming accessible for children. Following a paediatric European Union marketing authorisation, national Health Technology Assessment (HTA) agencies evaluate effectiveness, and safety of medicines to support decision on their cost and reimbursement. This study (a SIOPE Access to Medicines project) aimed to evaluate how these HTA evaluations take place for anticancer medicines indicated for paediatric use in Europe and to explore where the delays for market access originate.
We obtained HTA reports from the public domain for nine European countries for blinatumomab, dinutuximab beta and tisagenlecleucel. We evaluated the time elapsed between marketing authorisation for a paediatric indication and a national HTA decision and the nature of the decision.
Out of 23 HTA decisions (four countries without blinatumomab report), 18 were positive, two with restrictions, three negative. For blinatumomab, tisagenlecleucel and dinutuximab beta, the median time to an HTA decision after regulatory approval for paediatric use was 353 days (range 193-751), 141 days (range 77-517) and 515 days (range 0-780), respectively, with variability between countries. Dinutuximab beta and tisagenlecleucel were first introduced in children, but did not result in shorter time to HTA decision. For blinatumomab, marketing authorisation followed 1008 days after the indication in adults, with HTA applications submitted a median of 167 days later, and a recommendation after 145 days.
This study reveals ample variability in HTA decision making in nine European Union countries. Collaboration and alignment of required evidence is needed to facilitate robust scientific HTA assessments, also considering methodological challenges in paediatric oncology.

With the increasing incidence of cancer, poor access to affordable anticancer medicines has been a serious public health problem in China. To help address this issue, we assessed the availability, price and affordability of pharmacotherapy for cancer in public hospitals in the Jiangsu Province, China.
In 2012 and 2016, anticancer medicine availability and price information in the capital and five other cities was collected. A total of six cancer care hospitals, 26 tertiary general hospitals and 28 secondary general hospitals were sampled, using an adaptation of the World Health Organization/Health Action International methodology. Data was collected for the anticancer medicines in stock at the time of the surveys. Prices were expressed as inflation-adjusted median unit prices (MUPs). Medicine was affordable if the overall cost of all the prescribed anticancer medicines was less than 20% of the household\'s capacity to pay. We used generalized estimating equations to estimate the significance of differences in availability from 2012 to 2016 and the Wilcoxon rank test to estimate the significance of differences in MUPs. Multivariate logistic regression was computed to measure predictors of affordability.
From 2012 to 2016 there was a significant decrease in the mean availability of originator brands (OBs) (from 7.79% to 5.71%, p = 0.012) and lowest-priced generics (LPGs) (36.29% to 32.67%, p = 0.009). The mean availability of anticancer medicines in secondary general hospitals was significantly lower than the cancer care, as well as in tertiary general hospitals. The MUPs of OBs (difference: -21.29%, p < 0.01) and their LPGs (-22.63%, p < 0.01) decreased significantly from 2012 to 2016. The OBs (16.67%) of all the anticancer medicines were found to be less affordable than LPGs (34.62% for urban residents and 30.77% for rural residents); their affordability varied among the different income regions. From 2012 to 2016, the proportion of LPGs with low availability and low affordability dropped from 30.77% to 19.23% in urban areas and 34.62% to 26.92% in rural areas, respectively. Generic substitution and medicine covered by basic medical insurance are factors facilitating affordability.
There were concerning decreases in the availability of anticancer medicines in 2016 from already low availability in 2012. Anticancer medicines were more affordable for the patients in high-income regions than the patients in low-income regions. Governments should consider using their bargaining power to reduce procurement prices and abolish taxes on anticancer medicines. Policy should focus on the special health insurance plan for low-income patients with cancer. The goal of drug policy should ensure that first-line generic drugs are available for cancer patients and preferentially prescribed.

Prime focus of this study was to evaluate the availability and affordability of originator brands (OBs) and lowest price generics (LPGs) of prescribed biologic and non-biologic anticancer medicines.
A descriptive, cross-sectional survey was conducted in 22 cancer-care hospitals (18 public hospitals and 4 private hospitals) and 44 private pharmacies in Punjab, Pakistan. Sampling population consisted of 4483 patients with cancer aged ≥18 years. The availability was determined by classifying anticancer medicines in four categories: absent/unavailability (medicines not present in any surveyed facility), low availability (medicines present in <50% of surveyed facilities), fairly high availability (medicines present in 50%-74% of surveyed facilities) and high availability (medicines present in >75% of surveyed facilities). Medicines were affordable if overall cost of all the prescribed anticancer medicines were 20% of the household capacity to pay. Data were analysed by using Statistical Packages for Social Sciences (IBM SPSS Statistics for Windows, V.21.0).
A total of 5060 patients with cancer were approached out of which 4483 patients were included in the survey. Overall, 10 103 anticancer drugs were prescribed. Among them, 96.3% were non-biologics and 3.7% were biologics. Oncologists were reluctant to prescribe biologics due to high prices. 58.1% of non-biologics were affordable; whereas, the affordability of biologics was 3.3%. A total of 43.9% of both biologic and non-biologic OBs were available; whereas, their affordability was 44.2%. On the other hand, the availability of LPGs was 21.3%, and their affordability was 66.1%. For low-income patients, the affordability of non-biologics was 31.6% and the affordability of biologics was 1.1%.
Most of the patients with cancer were prescribed non-biologics due to their low price and better affordability. In contrast to OBs, LPGs of both biologics and non-biologics had less availability but more affordability.

Availability and affordability of anticancer medicines is a matter of great concern especially for low and middle income countries e.g., Pakistan. Prime focus of this study was to evaluate the availability of anticancer medicines in public and private sectors, and their affordability among patients with different income levels.
A descriptive, cross-sectional survey was conducted in 22 cancer care hospitals (18 public hospitals and 04 private hospitals) and 44 private pharmacies in Punjab, Pakistan. All (n = 4400) participants were ≥18 years of age. Data were collected at different intervals and analyzed by using Statistical Packages for Social Sciences (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) RESULTS: A total of 4913 patients were approached, and 4400 responded to the survey (response rate = 89.6%). Non-hodgkin lymphoma (12.3%), breast cancer (8.6%), and leukemia (7.6%) were the most prevailing cancers. Conventional medicines like cisplatin, cyclophosphamide, and etoposide were the most prescribed medicines. Oncologists were reluctant to prescribe newer anticancer medicines due to high prices. Originator brands (OBs) were more readily available (52.5%) but less affordable (53.4%); whereas, lowest price generics (LPGs) were less available (28.1%) but more affordable (67.9%). Anticancer medicines were more affordable by the high income class patients than the low income class patients.
The availability of both OBs and LPGs was greater at private hospitals and pharmacies as compared to public hospitals. The high income class had more affordability of both OBs and LPGs; however, LPGs were more affordable for all income classes.

The lack of efficacy is a major cause of medicine\'s development failure at the clinical phase, which may lead to question, among other aspects, the translation of the non-clinical data into humans. The objectives of the work here presented were (i) to get an overview (based on public assessment reports) of the nature of the non-clinical efficacy-related studies presented to the regulatory authorities at the marketing authorization application\'s stage for a group of approved anticancer human medicines (15 in total) and (ii) to conduct a retrospective analysis of such studies in terms of any identified insufficiencies and consistency with the current regulatory non-clinical guidelines. Each medicine has been tested in a number of in vitro assays and animal studies, which, all together, are judged to be capable of providing information on the activity of the active substance and demonstrating an anti-tumour effect, as well as to be generally consistent with the available, although limited detailed, guidance. In spite of this, some aspects were identified which could have a potential impact on the translation on non-clinical data into humans, namely, apparent insufficiencies in terms of animal model/human bridging data/knowledge and in vivo data on pharmacokinetics/pharmacodynamics relationships.

BACKGROUND: The availability and affordability of safe, effective, high-quality, affordable anticancer therapies are a core requirement for effective national cancer control plans.
METHODS: Online survey based on a previously validated approach. The aims of the study were to evaluate (i) the availability on national formulary of licensed antineoplastic medicines across the globe, (ii) patient out-of-pocket costs for the medications, (iii) the actual availability of the medication for a patient with a valid prescription, (iv) information relating to possible factors adversely impacting the availability of antineoplastic agents and (v) the impact of the country\'s level of economic development on these parameters. A total of 304 field reporters from 97 countries were invited to participate. The preliminary set of data was posted on the ESMO website for open peer review and amendments have been incorporated into the final report.
RESULTS: Surveys were submitted by 135 reporters from 63 countries and additional peer-review data were submitted by 54 reporters from 19 countries. There are substantial differences in the formulary availability, out-of-pocket costs and actual availability for many anticancer medicines. The most substantial issues are in lower-middle- and low-income countries. Even among medications on the WHO Model List of Essential Medicines (EML) the discrepancies are profound and these relate to high out-of-pocket costs (in low-middle-income countries 32.0% of EML medicines are available only at full cost and 5.2% are not available at all, and for low-income countries, the corresponding figures are even worse at 57.7% and 8.3%, respectively).
CONCLUSIONS: There is wide global variation in formulary availability, out-of-pocket expenditures and actual availability for most licensed anticancer medicines. Low- and low-middle-income countries have significant lack of availability and high out-of-pocket expenditures for cancer medicines on the WHO EML, with much less availability of new, more expensive targeted agents compared with high-income countries.