Changes in Availability and Affordability of Therapeutic Monoclonal Antibodies After New Medical Reform in Hubei Province, China

Abstract

Monoclonal antibody (mAb) refers to an immunoglobulin that binds to a specific 8 epitope on an antigen to exert its immunological effect [1] . In 1986, the first therapeutic 9 mAb Orthoclone OKT3 was approved by the US FDA for the prevention of renal is also facing with the problem of high drug prices. Financial unaffordability is 16 equivalent to no drug available to the patient. 17 In order to improve the availability and affordability of high-value drugs for  average [14]. Taken into account the differences in geographical location and economic 20 levels of cities in Hubei province, the surveyed hospitals were selected from prefecture-21 level cities of three distinct economic levels from five locations: East, south, west, north, 22 and central. In each city, secondary and tertiary public general hospitals were 23 investigated. China's primary hospitals mainly provide essential drugs and do not cover 24 therapeutic mAbs, and therefore they were not selected. For the selection of secondary 25 and tertiary hospitals in each city, all hospitals were surveyed in cities with fewer than 1 four public general hospitals. In cities with more than four public general hospitals, all 2 hospitals were enumerated, and four secondary and tertiary general hospitals were 3 randomly selected.

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In May 2016, we selected five prefecture-level cities at three economic levels:   Table 1 lists the general 16 information on the indications, targets, and supply sources of the 13 mAbs [16]. Each   The standard for assessing the affordability of medicines is the standard cost of 16 drugs for a course of treatment and its equivalence to multiples of the minimum daily 17 wage of non-technical government workers, that is, the affordability of medicines is for acute symptoms, and 30 days for chronic symptoms [17]. The retail unit price of a 11 drug is the median retail price per unit of a mAb sold by the hospitals surveyed. In this 12 study, the median affordability value of a drug can be calculated by the retail price of 13 the drug collected from two hospitals or more. In 2016, the per capita daily disposable 14 income of Hubei residents was ¥59.7 CNY, compared with ¥70.7 CNY in 2018 [14]. 15 We then used the Chi-Square test to calculate the significance of the difference in the 16 availability and price distribution of 13 mAbs before and after the NMR, respectively.  Table 2 presents the changes in the availability of 13 mAbs in the general hospitals of 2 Hubei province before and after the NMR. Of 13 mAbs, 11 were available and two 3 were unavailable before and after NMR. After the NMR, the average availability of 13 4 mAbs was increased by 6.7%, from 10.4% in 2016 to 17.1% in 2018 and was still at 5 the very low level. The availability of rituximab, trastuzumab, bevacizumab was 6 increased by greater than 10%.

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In 2016, the availability of 13 mAbs was less than 30%. In 2018, there were three 8 drugs with an availability of more than 40%, namely adalimumab, tozumab, and The median retail price of 10 mAbs available in 2016 in the 28 hospitals was ¥7199.5 16 CNY, and the median unit price was ¥581.8 CNY / mg (Table 3). Among them, the drug 17 with the highest unit price was ranbizumab, reaching a price as high as ¥4877.8 CNY / . Therefore, the out-of-pocket ratio of the 24 six mAbs covered by our study that fall under the Class B list was set at 30%. Our 25 results showed that after the costs of the six mAbs were reimbursed by medical 1 insurance, the average actual out-of-pocket cost was ¥7,467 CNY, which was reduced 2 by ¥17,424.3 CNY compared with the pre-reimbursement cost. The average number of 3 burden days of the six mAbs after medical insurance reimbursement was 106 days, 4 which was 246 days less than that before the NMR. (see additional file4) 5 After insurance reimbursement, the average burden days for one course of 6 treatment with 10 therapeutic mAbs was 151 days, which was 529 days less than that 7 before the NMR. Among these, the number of burden days for one course of treatment 8 was reduced by total 1945 days for rituximab and 1123 days for bevacizumab.

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Barriers to the accessibility of mAb drugs after NMR 10 As shown in Tables 2 and 4, although the availability and affordability of mAbs were 11 improved following the NMR, they were still at low level. Figure 1    of NBMI was very limited, and the copay rate for their own medicines was still high.

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After the NMR, the availability and affordability of therapeutic mAbs in Hubei province have improved significantly, but the levels are still low. There seems to be no 1 synergy between these reform policies to promote the availability and affordability of 2 the mAbs in the public hospitals. Therefore, in order to optimize the NMR policy 3 system and further increase the accessibility of mAbs, it is necessary to take the 4 following measures, including substantially promoting the technological advancement 5 of research and production for high-quality mAbs and generics, strengthening evidence- To exactly fulfill the WHO's survey requirements on the availability and affordability 11 of medicines, the survey should further include regional public hospitals and private 12 retail pharmacies. In 2016, 71% of China's drug sales came from medical institutions.

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Due to the high price of therapeutic mAbs and no settlement of medical insurance fund 14 in retail pharmacies, it is highly risky for private retail pharmacies to maintain the 15 supply of therapeutic mAbs, and relatively few retail pharmacies provide the drugs 16 based on the results of our preliminary survey in Wuhan city in 2016. Therefore, our 17 study only conducted data surveys in public hospitals and did not investigate private 18 retail pharmacies. As a result, the mAb availability can be biased in Hubei Province. 19 Also, this study applied the disposable income per capita of residents instead of the 20 minimum daily wage of non-technical government workers to calculate drug 21 affordability. Since the disposable income per capita of average residents is generally 22 lower than the minimum daily wage of non-technical government workers, the 23 affordability of therapeutic mAbs could be under-estimated. 24 Moreover, information on the availability and price of medicines was only collected 25 on the day of the survey at each hospital, and thus cannot reflect the average monthly 1 or yearly availability of mAbs and their prices.