Consumption and cost trends of EGFR TKIs
The number of DDDs of all TKIs changed slightly from 2010 to 2015, but kept increasing since 2016. The number of DDDs increased by 69.0% in 2016, 100.0% in 2017, 159.4% in 2018, and 59.5% in 2019 (Fig. 1A). Accordingly, expenditure also kept increasing significantly (Fig. 1B). The average DDC of all TKIs changed slightly from 2010 to 2015, but decreased significantly from 2016 to 2017 (Fig. 1A). The DDC decreased by 27.3% in 2016 and 31.9% in 2017 (Fig. 1C). The average DDC changed little in 2018 and 2019 (Fig. 1C).
Consumption of three generations of EGFR TKIs
The number of DDDs (Fig. 2A), expenditure (Fig. 2B) and DDC of the first-generation TKIs changed little from 2010 to 2015. The DDC of the first-generation TKIs decreased gradually (Fig. 2C), while their number of DDDs increased year by year since 2016 (Fig. 2A). Overall, the number of DDDs and expenditure of the first-generation TKIs made up always took most of the total consumption from 2010 to 2019. The second-generation TKI (afatinib) entered the market since 2018, and the number of DDDs (Fig. 2A) and expenditure (Fig. 2B) increased significantly in 2019. The third-generation TKI (osimertinib) was launched in 2019, and its DDC was significantly higher than those of other TKIs.
Consumption of each type of EGFR TKIs
Before 2018, gefitinib, erlotinib, and icotinib were on the market. Their number of DDDs, expenditure, and DDC changed slightly from 2010 to 2015. The number of DDDs of these three drugs showed an ascending trend (Fig. 3A), while the DDC showed a descending trend since 2016 (Fig. 3C). The number of DDDs of gefitinib, which was the most widely applied type, accounted for more than 50% of the total number of DDDs from 2010 to 2018 (Fig. 3A). In 2019, the number of DDDs of gefitinib slightly increased, but only made up 36.96% of the total number of DDDs (Fig. 3A). Icotinib came into use in 2011, and its consumption was low from 2011 to 2015. The number of DDDs increased significantly (Fig. 3A), but the DDC of icotinib decreased annually from 2016 to 2019 (Fig. 3C). The number of DDDs of erlotinib has been always less than that of gefitinib (Fig. 3A). The DDC of erlotinib decreased significantly in 2017(Fig. 3C), but its number of DDDs increased slightly (Fig. 3A). Afatinib came into market in 2018 and osimertinib in 2019, but their consumptions were relatively low (Fig. 3A and 3B). The DDC of osimertinib was the highest in all the TKIs (Fig. 3C).
Relationship between DDC and DDDs
Over the past decade, the price of the first-generation TKIs has reduced, hence we analyzed the relationship between their DDC and number of DDDs. The DDC of gefitinib decreased gradually, while the number of DDDs increased continuously since 2016. The DDC of gefitinib had a negative correlation with its number of DDDs (R2 = 0.7663, P = 0.0009) (Fig. 4A). A negative correlation existed between the DDC and number of DDDs for erlotinib (R2 = 0.5892, P = 0.0095, Fig. 4B) and icotinib (R2 = 0.6682, P = 0.0071, Fig. 4C).
As gefitinib, icotinib and erlotinib were enrolled in the national insurance in 2017, self-paid cost (out of pocket cost) was the real expenditure patients paid. A negative correlation existed between self-paid DDC and number of DDDs for gefitinib (R2 = 0.7826, P = 0.0007, Fig. 4D), erlotinib (R2 = 0.5509, P = 0.0140, Fig. 4E) and icotinib (R2 = 0.8389, P = 0.0005, Fig. 4F).
Influence of insurance and price on drug consumption
Previous studies have reported that insurance reimbursement and drug price are impact factors of drug consumption. Hence, we analyzed their influence of reimbursement and price on the number of DDDs of TKIs. In July 2016, the DDC of gefitinib began to drop, and the number of DDDs kept increasing significantly in the subsequent 6 months (Fig. 5 and Table S1). Similar changes were also observed in icotinib. In January 2017, gefitinib and icotinib were covered by health insurance, with a reimbursement rate of 50%. Their number of DDDs both increased in the next 6 months (Fig. 5 and Table S1). In July 2017, erlotinib were covered by the national health insurance, and its DDC dropped. Thereafter, its number of DDDs increased by 175.55% (Fig. 5 and Table S1). In January 2019, afatinib and osimertinib were covered by the national health insurance, and their number of DDDs increased. In the same year, the prices of erlotinib and gefitinib fell, but their number of DDDs did not increase (Fig. 5 and Table S1).