Trends of Negotiated Targeted Anticancer Medicines Use in China: An Interrupted Time Series Analysis

Document Type : Original Article


1 Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China

2 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

3 Center for Strategic Studies, Chinese Academy of Engineering, Beijing, China


In order to relieve the financial burden of the patients in China, the Ministry of Health (MoH) conducted the first national price negotiation and successfully negotiated three expensive medicines including 2 targeted anticancer medicines (TAMs), icotinib and gefitinib. However, little evidence was available to demonstrate the impact of the national negotiation on TAMs use. The purpose of the study is to evaluate the implementation of the national price negotiation policy in China on TAMs use.
We used interrupted time series (ITS) design to examine the changes in the daily cost, the monthly hospital purchasing volume and spending of icotinib and gefitinib with pharmaceutical procurement data from 594 tertiary hospitals in 29 provinces of mainland China between January 2015 and July 2017. The period between May and July 2016 was applied to assess the impact of policy.

The daily cost of icotinib and gefitinib decreased by 50.08% (P < .001) and 53.89% (P < .001) 12 months after the national negotiation, respectively. In terms of volume, the negotiation was associated with increases in the trend of the monthly hospital purchasing volume of icotinib and gefitinib by 4.87 thousand defined daily doses (DDDs) (P < .001) and 6.89 thousand DDDs (P < .001). However, the monthly hospital purchasing spending of icotinib and gefitinib decreased rapidly by US$0.51 million (P < .010) and US$0.82 million (P < .050) following policy implementation, respectively.
The first national negotiation had successfully cut off the price of two negotiated TAMs and promoted TAMs use in China. In the future, government should conduct further price negotiations and include more medicines with clinical benefits into reimbursement schemes to alleviate patients’ financial burden and promote their access to essential treatment.


  1. World Health Organization (WHO). World Health Statistics 2018: Monitoring Health for the SDGs. WHO; 2018.
  2. Lu Y, Hernandez P, Abegunde D, Edejer T. The World Medicines Situation 2011. Medicine Expenditures. 2011.
  3. National Health Commission of the People’s Republic of China. China Health Statistical Yearbook 2018. Beijing: China Union Medical University Press; 2018.
  4. China National Health Development Research Center of Ministry of Health of the People’s of Republic of China. China National Health Accounts Report; 2013.
  5. Song Y, Bian Y, Petzold M, Li L, Yin A. Effects of the National Essential Medicine System in reducing drug prices: an empirical study in four Chinese provinces. J Pharm Policy Pract. 2014;7(1):12. doi:10.1186/2052-3211-7-12
  6. Sun J, Hu CJ, Stuntz M, Hogerzeil H, Liu Y. A review of promoting access to medicines in China - problems and recommendations. BMC Health Serv Res. 2018;18(1):125. doi:10.1186/s12913-018-2875-6
  7. Lee C, Sun H, Guan Q, Wasserman M. The effect of China's basic medical insurance schemes on health service utilization. Value Health. 2014;17(7):A428. doi:10.1016/j.jval.2014.08.1077
  8. Meng Q, Fang H, Liu X, Yuan B, Xu J. Consolidating the social health insurance schemes in China: towards an equitable and efficient health system. Lancet. 2015;386(10002):1484-1492. doi:10.1016/s0140-6736(15)00342-6
  9. Ward E, Halpern M, Schrag N, et al. Association of insurance with cancer care utilization and outcomes. CA Cancer J Clin. 2008;58(1):9-31. doi:10.3322/ca.2007.0011
  10. State Council of the People’s of Republic of China. Advances in national medicine negotiation in China. Accessed September 23, 2019. Published 2016.
  11. National Health Commission of the People’s Republic of China. China Health Statistical Yearbook 2016. Beijing: China Union Medical University; 2016.
  12. Yu H. Universal health insurance coverage for 1.3 billion people: what accounts for China's success? Health Policy. 2015;119(9):1145-1152. doi:10.1016/j.healthpol.2015.07.008
  13. State Council of the People’s of Republic of China. Results of national medicine negotiation in China. Accessed September 23, 2019. Published 2016.
  14. WHO Collaborating Centre for Drug Statistics Methodology. New DDD Index 2019., Published September 23, 2019.
  15. National Medical Products Administration of the People's Republic of China. Collection of Drugs Marketed in China. Published 2019.
  16. National Bureau of Statistics of China. Time Series Data -- Monthly Data: Exchange Rate.
  17. Zheng RS, Sun KX, Zhang SW, et al. [Report of cancer epidemiology in China, 2015]. Zhonghua Zhong Liu Za Zhi. 2019;41(1):19-28. doi:10.3760/cma.j.issn.0253-3766.2019.01.005
  18. Zhang X, Liu S, Liu Y, et al. Economic burden for lung cancer survivors in urban China. Int J Environ Res Public Health. 2017;14(3):308. doi:10.3390/ijerph14030308
  19. Azzoli CG, Temin S, Aliff T, et al. 2011 Focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 2011;29(28):3825-3831. doi:10.1200/jco.2010.34.2774
  20. Zhi X, Shi Y, Yu J. [Standards for the diagnosis and treatment of primary lung cancer (2015 version) in China]. Zhonghua Zhong Liu Za Zhi. 2015;37(1):67-78. 
  21. National Bureau of Statistics of China. China Statistical Yearbook, 2016. Beijing: China Union Medical University Press; 2016.
  22. Song Y, Zhou Q, Zhang X, et al. Factors associated with gene aberration test status and treatment decision in patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer: a multicenter survey in China (CTONG 1506). Lung Cancer. 2018;123:7-13. doi:10.1016/j.lungcan.2018.06.008
  23. Diao Y, Qian J, Liu Y, et al. How government insurance coverage changed the utilization and affordability of expensive targeted anti-cancer medicines in China: an interrupted time-series study. J Glob Health. 2019;9(2):020702. doi:10.7189/jogh.09.020702
  24. Wagner AK, Soumerai SB, Zhang F, Ross-Degnan D. Segmented regression analysis of interrupted time series studies in medication use research. J Clin Pharm Ther. 2002;27(4):299-309. doi:10.1046/j.1365-2710.2002.00430.x
  25. Lopez Bernal J, Soumerai S, Gasparrini A. A methodological framework for model selection in interrupted time series studies. J Clin Epidemiol. 2018;103:82-91. doi:10.1016/j.jclinepi.2018.05.026
  26. Guan X, Tian Y, Ross-Degnan D, Man C, Shi L. Interrupted time-series analysis of the impact of generic market entry of antineoplastic products in China. BMJ Open. 2018;8(7):e022328. doi:10.1136/bmjopen-2018-022328
  27. New ATC codes 2019. WHO Collaborating Centre for Drug Statistics Methodology; 2019. Accessed September 23, 2019.
  28. National Bureau of Statistics of China. Time Series Data -- Annual Data: Exchange Rate.
  29. National Bureau of Statistics of China. Time Series Data -- Monthly Data: Consumer Price Index.
  30. Shiskin J, Allan H, John C. The X-11 Variant of the Census Method II Seasonal Adjustment. Document technique no15 du US Department of Commerce du Bureau of the Census; 1967.
  31. Zhang F, Wagner AK, Soumerai SB, Ross-Degnan D. Methods for estimating confidence intervals in interrupted time series analyses of health interventions. J Clin Epidemiol. 2009;62(2):143-148. doi:10.1016/j.jclinepi.2008.08.007
  32. Durbin J, Watson GS. Testing for serial correlation in least squares regression: I. Biometrika. 1950;37(3-4):409-428. doi:10.2307/2332391
  33. Kutner M, Nachtsheim C, Neter J. Applied Linear Regression Models. 4th ed. Chicago: Irwin/McGraw-Hill; 2004.
  34. National Health Commission of the People’s Republic of China. China Health Statistical Yearbook 2019. Beijing: China Union Medical University Press; 2019.
  35. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115-132. doi:10.3322/caac.21338
  36. Huang HY, Shi JF, Guo LW, et al. Expenditure and financial burden for common cancers in China: a hospital-based multicentre cross-sectional study. Lancet. 2016;388 Suppl 1:S10. doi:10.1016/s0140-6736(16)31937-7
  37. Zhao T, Cheng J, Chai J, et al. Inpatient care burden due to cancers in Anhui, China: a cross-sectional household survey. BMC Public Health. 2016;16:308. doi:10.1186/s12889-016-2995-z
  38. National Cancer Institute. Targeted Cancer Therapies 2019. 2019; Accessed September 23, 2019.
  39. Sledge GW Jr. What is targeted therapy? J Clin Oncol. 2005;23(8):1614-1615. doi:10.1200/jco.2005.01.016
  40. Chen Q, Jain N, Ayer T, et al. Economic burden of chronic lymphocytic leukemia in the era of oral targeted therapies in the United States. J Clin Oncol. 2017;35(2):166-174. doi:10.1200/jco.2016.68.2856
  41. Shih YT, Xu Y, Liu L, Smieliauskas F. Rising prices of targeted oral anticancer medications and associated financial burden on Medicare beneficiaries. J Clin Oncol. 2017;35(22):2482-2489. doi:10.1200/jco.2017.72.3742
  42. Ministry of Human Resources and Social Security of the People's Republic of China. Inclusion of 36 medicines by National Reimbursement Drug List. Accessed September 23, 2019. Published 2017.
  43. National Healthcare Security Administration of the People's Republic of China. Inclusion of 17 medicines by National Reimbursement Drug List. Accessed September 23, 2019. Published 2017.
  44. Tang M, Song P, He J. Progress on drug pricing negotiations in China. Biosci Trends. 2020;13(6):464-468. doi:10.5582/bst.2019.01339
  45. Howard DH, Bach PB, Berndt ER, Conti RM. Pricing in the market for anticancer drugs. J Econ Perspect. 2015;29(1):139-162. doi:10.1257/jep.29.1.139
  46. Shih YC, Smieliauskas F, Geynisman DM, Kelly RJ, Smith TJ. Trends in the cost and use of targeted cancer therapies for the privately insured nonelderly: 2001 to 2011. J Clin Oncol. 2015;33(19):2190-2196. doi:10.1200/jco.2014.58.2320
  47. Dusetzina SB, Conti RM, Yu NL, Bach PB. Association of prescription drug price rebates in Medicare Part D with patient out-of-pocket and federal spending. JAMA Intern Med. 2017;177(8):1185-1188. doi:10.1001/jamainternmed.2017.1885
  48. Frank RG, Newhouse JP. Should drug prices be negotiated under Part D of Medicare? and if so, how? Health Aff (Millwood). 2008;27(1):33-43. doi:10.1377/hlthaff.27.1.33
  49. Frank RG, Nichols LM. Medicare drug-price negotiation - why now . . . and how. N Engl J Med. 2019;381(15):1404-1406. doi:10.1056/NEJMp1909798
  50. Shao R, Ge Q, Xie J. Study on the price negotiation system of special medical insurance drugs in typical provinces and it. Journal of Guangdong Pharmaceutical University. 2017;33(4):518-521.
  51. (WHO) WHO. Technical Report: Pricing of Cancer Medicines and Its Impacts. 2018; Accessed March 1, 2019.
  52. Moye-Holz D, van Dijk JP, Reijneveld SA, Hogerzeil HV. The impact of price negotiations on public procurement prices and access to 8 innovative cancer medicines in a middle-income country: the case of Mexico. Value Health Reg Issues. 2019;20:129-135. doi:10.1016/j.vhri.2019.04.006
  53. Lauenroth VD, Kesselheim AS, Sarpatwari A, Stern AD. Lessons from the impact of price regulation on the pricing of anticancer drugs in Germany. Health Aff (Millwood). 2020;39(7):1185-1193. doi:10.1377/hlthaff.2019.01122
  54. Massard da Fonseca E, Bastos FI, Lopes G. Increasing access to oral anticancer medicines in middle-income countries: a case study of private health insurance coverage in Brazil. J Glob Oncol. 2016;2(1):39-46. doi:10.1200/jgo.2015.001917
  55. Mihajlović J, Dolk C, Postma MJ. Reimbursement of targeted cancer therapies within three different European health care systems. Value Health. 2014;17(7):A658-659. doi:10.1016/j.jval.2014.08.2409
  56. Su M, Zhou Z, Si Y, et al. Comparing the effects of China's three basic health insurance schemes on the equity of health-related quality of life: using the method of coarsened exact matching. Health Qual Life Outcomes. 2018;16(1):41. doi:10.1186/s12955-018-0868-0
  57. Fang H, Eggleston K, Hanson K, Wu M. Enhancing financial protection under China's social health insurance to achieve universal health coverage. BMJ. 2019;365:l2378. doi:10.1136/bmj.l2378
  58. China Charity Federation. Iressa Means–Tested Drug Donation. Accessed September 23, 2019.
  59. Wan Q, Zhang Y, WANG X. Results and Analysis of China National Health Accounts in 2013. Chinese Health Economics; 2015.
Volume 11, Issue 8
August 2022
Pages 1489-1495
  • Receive Date: 23 October 2020
  • Revise Date: 29 January 2021
  • Accept Date: 18 April 2021
  • First Publish Date: 09 June 2021