Application of Real-World Evidence in the Approval of Antitumor Drugs

Abstract

Objective To study the information of real-world evidence (RWE) that can make up the deficiency of RCT results, the unfeasibility of some trials and the possible ethical problems, and to promote the approval of RWE for anti-tumor drugs. Methods Literature analysis, policy analysis and comparative analysis were used. Results and Conclusion The studies and application of RWE in the United States, the European Union, and China were reviewed. The approval of anti-tumor drugs supported by RWE was generally used for external control groups in single arm trials, clinical efficacy and safety of adjuvant support drugs, or background analysis. The types of approvals included innovative anti-tumor drugs, supplemented indications of the approved drugs, expanding patient population, and combination medication. This study can provide reference for the approval of anti-tumor drugs using RWE in China. It is recommended to combine traditional RCT with RWE to promote the approval of anti-tumor drugs.

Keywords

real-world evidence / antitumor drugs / approval

References

[1] U.S. Food and Drug Administration. Framework for FDA’s Real-World Evidence Program[EB/OL]. (2018-12-06)[2021-01-31]. https://www.fda.gov/media/120060/download.

[2] Cave A, Kurz X, Arlett P. Real-world data for regulatory decision making: Challenges and possible solutions for Europe[J]. Clinical Pharmacology& Therapeutics, 2019, 106 (1): 36-39.

[3] National Medical Products Administration. Guidelines for Real-World Evidence Supporting Drug Development and Review (Trial)[EB/OL]. (2020-01-03)[2021-01-31]. https://www.cde.org.cn/zdyz/domesticinfopage?zdyzIdCODE=db4376287cb678882a3f6c8906069582.

[4] Kim ES, Bruinooge SS, Roberts S, et al. Broadening eligibility criteria to make clinical trials more representative: American society of clinical oncology and friends of cancer research joint research statement[J]. Journal of Clinical Oncology, 2017, 35 (33): 3737-3744.

[5] Tang Ling, Zhou Ming, Xia Lin, et al. Review and consideration of patient-centered antitumor drug clinical development[J]. Chinese Clinical Oncology, 2021, 26 (7): 577-582.

[6] Zhao Yunxia, Shao Mingyi, Chen Xiaoqi, et al. Exploring the authenticity and influencing factors of real-world data[J]. Journal of Traditional Chinese Medicine, 2021, 62 (4): 303-306+311.

[7] Klonoff DC. The new FDA real-world evidence program to support development of drugs and biologics[J]. Journal of Diabetes Science and Technology, 2020, 14 (2): 345-349.

[8] Bolislis WR, Fay M, Kühler TC. Use of real-world data for new drug applications and line extensions[J]. Clinical Therapeutics, 2020, 42 (5): 926-938.

[9] Burcu M, Dreyer NA, Franklin JM, et al. Real-world evidence to support regulatory decision-making for medicines: Considerations for external control arms[J]. Pharmacoepidemiology and Drug Safety, 2020, 29 (10): 1228-1235.

[10] Ming Dandan, Li Jun, Xu Xuan, et al. Real-world research methods and their application in clinical research[J]. Chinese Pharmacy, 2018, 29 (15): 2138-2143.

[11] Wang Jingwen, Shao Mingyi, Fu Yu, et al. Analysis and reflection on the design of real world study scheme in China[J]. Chinese Journal of Traditional Chinese Medicine, 2022, 37 (4): 2125-2128.

[12] Qin Xueni, Chen Weisheng, Shao Hua, et al. Application and research method of real world research in the medical field[J]. Pharmaceutical Progress, 2021, 45 (7): 512-523.

[13] Khozin S, Kim G, Pazdur R. Regulatory watch: From big data to smart data: FDA’s INFORMED initiative[J]. Nature Reviews Drug Discovery, 2017, 16 (5): 306.

[14] Hershman DL, Wright JD. Comparative effectiveness research in oncology methodology: Observational data[J]. Journal of Clinical Oncology, 2012, 30 (34): 4215-4222.

[15] Andre EB, Reynolds R, Caubel P, et al. Trial designs using real-world data: The changing landscape of the regulatory approval process[J]. Pharmacoepidemiology and Drug Safety, 2020, 29 (10): 1201-1212.

[16] Raphael MJ, Gyawali B, Booth CM. Real-world evidence and regulatory drug approval[J]. Nature Reviews Clinical Oncology, 2020, 17 (5): 271-272.

[17] Feinberg BA, Gajra A, Zettler ME, et al. Use of real-world evidence to support FDA approval of oncology drugs[J]. Value Health, 2020, 23 (10): 1358-1365.

[18] Arondekar B, Duh MS, Bhak RH, et al. Real-world evidence in support of oncology product registration: A systematic review of new drug application and biologics license application approvals from 2015-2020[J]. Clinical Cancer Research, 2021, 28 (1): 27-35.

[19] Duh MS, Bhak R, Arondekar B, et al. Evaluating the role of real-world evidence for oncology product registration in the United States: A systematic review of approvals by the food and drug administration from 2015-2019[J]. Value in Health, 2020, 23: 59.

[20] EMA. HMA-EMA joint big data task force: Summary report[EB/OL]. (2019-02-13)[2021-01-31]. https://www.ema.europa.eu/en/documents/minutes/hma/ema-joint-task-force-big-data-summary-report_en.pdf.

[21] Garside J, Healy N, Besson H, et al. PHEDRA: Using real-world data to analyze treatment patterns and ibrutinib effectiveness in hematological malignancies[J]. Journal of Comparative Effectiveness Research, 2018, 7 (1): 29-38.

[22] Dreyer NA. Advancing a framework for regulatory use of real-world evidence: When real is reliable[J]. Therapeutic Innovation & Regulatory Science, 2018, 52 (3): 362-368.

[23] Eskola SM, Leufkens HGM, Bate A, et al. Use of real-world data and evidence in drug development of medicinal products centrally authorized in Europe in 2018-2019[J]. Clinical Pharmacology and Therapeutics, 2022, 111 (1),310-320.

[24] Center For Drug Evaluation. Real-World Evidence Supports Fundamental Considerations for Drug Development (Exposure Draft)[EB/OL]. (2019-05-29)[2021-01-31]. https://www.cde.org.cn/main/news/viewInfoCommon/7e6fb9fc3f066a966a02130f24dbff1c.

[25] National Medical Products Administration, National Development and Reform Commission. Implementation Plan for Supporting the Construction of Boao Lecheng International Medical Tourism Pilot Zone[EB/OL]. (2019-09-10)[2021-01-31]. http://www.gov.cn/xinwen/2019-09/17/5430452/files/7d1f580ed40b4853a061f1b5da0e23d2.pdf.

[26] National Medical Products Administration. Real-World Data Guidelines for Generating Real-World Evidence (Trial)[EB/OL]. (2021-04-15)[2021-01-31]. https://www.cde.org.cn/zdyz/domesticinfopage?zdyzIdCODE=7d2e46cea0e459358257760383526e9d.

[27] Ren Yan, Liang Yuanbo, Liu Mimi. Exploration and practice of real-world data studies on innovative medical products in Boao Lecheng: Analysis based on Chinese first case of approved medical device using domestic real-world data[J]. Chinese Journal of Evidence-Based Medicine, 2020, 20 (10): 1117-1123.

[28] Li Can, Wu Chenyue, Han Wei. Considerations on real-world evidence for CMC of new TCM drugs[J]. China Food & Drug Administration Magazine, 2021 (11): 103-107.

[29] An Na, Han Ling, Chen Pingyan. Reflections on real world research under the evidence system of “three combinations” registration and evaluation of new traditional Chinese medicine[J]. Chinese Journal of New Drugs, 2022, 31 (14): 1359-1363.

[30] Sheng Song, Huang Ye. The advantages and limitations of conducting research on traditional Chinese medicine based on the real world[J]. Chinese Journal of Integrative Medicine on Cardio-/Cerebrovascular Disease, 2023, 21 (2): 377-379.

[31] Ming Dandan, Li Jun, Xu Xuan, et al. Methods of real-world research and their applications in clinical research[J]. China Pharmacy, 2018, 29 (15): 2138-2143.

[32] Boyle JM, Hegarty G, Frampton C, et al. Real-world outcomes associated with new cancer medicines approved by the Food and Drug Administration and European Medicines Agency: A retrospective cohort study[J]. European Journal of Cancer, 2021, 155: 136-144.