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The number of clinical trials conducted in mainland China, including investigator-initiated trials (IITs), has increased rapidly in recent years. However, there are few data on the characteristics of cancer-related IITs. We performed a comprehensive analysis of the landscape of cancer-related IITs in mainland China in the past decade. All cancer-related IITs registered on two clinical trial registries in the United States (www.clinicaltrials.gov, CT.gov) and mainland China (www.chictr.org.cn, ChiCTR) from 2010 to 2019 were identified. IITs were reviewed manually to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. A total of 8199 cancer-related IITs were identified. The number of trials registered annually increased over time, especially in the last 5 years. Although interventional studies were predominant, randomized double-blind studies accounted for only 8% of IITs. In the past decade, the trend for interventional studies conducted with different drugs increased year on year, although the increase in hormonal therapy IITs was not significant. Additionally, cancer-related IITs were unevenly geographically distributed, with half concentrated in the economically developed cities Shanghai, Beijing, and Guangdong. We also found an increase in registration before participant enrollment (64.9% for trials in conducted in 2015–2019 vs. 40.2% in 2010–2014, p < 0.001) and data monitoring committee use (44.5% vs. 40.0%, p = 0.001) and a decrease in randomization (51.5% vs. 62.7%, p < 0.001) and funding (36.4% vs. 56.3%, p < 0.001) between these periods. We also observed changes in intervention type (decrease in cytotoxic drug therapy [34.8% vs. 48.9%, p < 0.001]; increase in targeted therapy [17.8% vs. 14.2%, p = 0.004], immune checkpoint inhibitor therapy [6.6% vs. 0.0%, p < 0.001], and immune cell therapy [9.6% vs. 4.5%, p < 0.001]). Details of cancer-related IITs conducted during the past decade illustrate the merits of oncology research in mainland China. Although the increased quantity of IITs is encouraging, limitations remain regarding the quality of clinical trials, regional imbalances, and funding allocation.
The number of clinical trials conducted in mainland China, including investigator-initiated trials (IITs), has increased rapidly in recent years. However, there are few data on the characteristics of cancer-related IITs. We performed a comprehensive analysis of the landscape of cancer-related IITs in mainland China in the past decade. All cancer-related IITs registered on two clinical trial registries in the United States (www.clinicaltrials.gov, CT.gov) and mainland China (www.chictr.org.cn, ChiCTR) from 2010 to 2019 were identified. IITs were reviewed manually to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. A total of 8199 cancer-related IITs were identified. The number of trials registered annually increased over time, especially in the last 5 years. Although interventional studies were predominant, randomized double-blind studies accounted for only 8% of IITs. In the past decade, the trend for interventional studies conducted with different drugs increased year on year, although the increase in hormonal therapy IITs was not significant. Additionally, cancer-related IITs were unevenly geographically distributed, with half concentrated in the economically developed cities Shanghai, Beijing, and Guangdong. We also found an increase in registration before participant enrollment (64.9% for trials in conducted in 2015–2019 vs. 40.2% in 2010–2014, p < 0.001) and data monitoring committee use (44.5% vs. 40.0%, p = 0.001) and a decrease in randomization (51.5% vs. 62.7%, p < 0.001) and funding (36.4% vs. 56.3%, p < 0.001) between these periods. We also observed changes in intervention type (decrease in cytotoxic drug therapy [34.8% vs. 48.9%, p < 0.001]; increase in targeted therapy [17.8% vs. 14.2%, p = 0.004], immune checkpoint inhibitor therapy [6.6% vs. 0.0%, p < 0.001], and immune cell therapy [9.6% vs. 4.5%, p < 0.001]). Details of cancer-related IITs conducted during the past decade illustrate the merits of oncology research in mainland China. Although the increased quantity of IITs is encouraging, limitations remain regarding the quality of clinical trials, regional imbalances, and funding allocation.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49. https://doi.org/10.3322/caac.21660
Konwar M, Bose D, Gogtay NJ, Thatte UM. Investigator-initiated studies: challenges and solutions. Perspect Clin Res. 2018;9(4):179–83. https://doi.org/10.4103/picr.PICR_106_18
Speich B, Logullo P, Deuster S, Marian IR, Moschandreas J, Taji Heravi A, et al. A meta-research study revealed several challenges in obtaining placebos for investigator-initiated drug trials. JCE. 2021;131:70–8. https://doi.org/10.1016/j.jclinepi.2020.11.007
Kuboki Y, Nishina T, Shinozaki E, Yamazaki K, Shitara K, Okamoto W, et al. TAS-102 plus bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE): an investigator-initiated, open-label, single-arm, multicentre, phase 1/2 study. Lancet Oncol. 2017;18(9):1172–81. https://doi.org/10.1016/S1470-2045(17)30425-4
Li N, Huang HY, Wu DW, Yang ZM, Wang J, Wang JS, et al. Changes in clinical trials of cancer drugs in mainland China over the decade 2009-18: a systematic review. Lancet Oncol. 2019;20(11):e619–26. https://doi.org/10.1016/S1470-2045(19)30491-7
Tsikkinis A, Cihoric N, Giannarini G, Hinz S, Briganti A, Wust P, et al. Clinical perspectives from randomized phase 3 trials on prostate cancer: an analysis of the ClinicalTrials.gov database. Eur Urol Focus. 2015;1(2):173–84. https://doi.org/10.1016/j.euf.2015.05.003
Subramanian J, Regenbogen T, Nagaraj G, Lane A, Devarakonda S, Zhou G, et al. Review of ongoing clinical trials in non-small-cell lung cancer: a status report for 2012 from the ClinicalTrials.gov web site. J Thorac Oncol. 2013;8(7):860–5. https://doi.org/10.1097/JTO.0b013e318287c562
Petrelli F, Damato A, Perego G, Ghidini A, Daniele G, Pinto C. Past, present and future use of cytotoxic agents in oncology practice: a systematic review of PubMed and ClinicalTrials.gov databases. J Oncol Pharmacy Pract. 2020;26(8):2069–72. https://doi.org/10.1177/1078155220951237
Ito T. Differences in Investigator-initiated trials between Japan and other countries: analyses of clinical trials sponsored by academia and government in the ClinicalTrials.gov registry and in the three Japanese registries. PLoS One. 2016;11(2):e0148455. https://doi.org/10.1371/journal.pone.0148455
Mathieu S. Comparison of registered and published primary outcomes in randomized controlled trials. JAMA. 2009;302(9):977–84. https://doi.org/10.1001/jama.2009.1242
Califf RM. Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010. JAMA. 2012;307(17):1838–47. https://doi.org/10.1001/jama.2012.3424
Yang G, Wang Y, Zeng Y, Gao GF, Liang X, Zhou M, et al. Rapid health transition in China, 1990-2010: findings from the global burden of disease study 2010. The Lancet. 2013;381(9882):1987–2015. https://doi.org/10.1016/s0140-6736(13)61097-1
Wang C, Liu Q. A turning point for clinical research in China? The Lancet. 2013;382(9895):835–6. https://doi.org/10.1016/s0140-6736(13)61804-8
Zhang S, Sun K, Zheng R, Zeng H, Wang S, Chen R, et al. Cancer incidence and mortality in China, 2015. J Natl Cancer Center. 2021;1(1):2–11. https://doi.org/10.1016/j.jncc.2020.12.001
Force LM, Abdollahpour I, Advani SM, Agius D, Ahmadian E, Alahdab F, et al. Collaborators GBDCC. The global burden of childhood and adolescent cancer in 2017: an analysis of the global burden of disease study 2017. Lancet Oncol. 2019;20(9):1211–25. https://doi.org/10.1016/S1470-2045(19)30339-0
Jin Y, Lyu Q. Basic research in childhood cancer: progress and future directions in China. Cancer Lett. 2020;495:156–64. https://doi.org/10.1016/j.canlet.2020.08.014
Liu X, Zhang Y, Tang LL, Le QT, Chua MLK, Wee JTS, et al. Characteristics of radiotherapy trials compared with other oncological clinical trials in the past 10 years. Jama Oncol. 2018;4(8):1073–9. https://doi.org/10.1001/jamaoncol.2018.0887
Parseghian CM, Tam AL, Yao J, Ensor J, Ellis LM, Raghav K, et al. Assessment of reported trial characteristics, rate of publication, and inclusion of mandatory biopsies of research biopsies in clinical trials in oncology. Jama Oncol. 2019;5(3):402–5. https://doi.org/10.1001/jamaoncol.2018.4640
Hirsch BR, Califf RM, Cheng SK, Tasneem A, Horton J, Chiswell K, et al. Characteristics of oncology clinical trials insights from a systematic analysis of ClinicalTrials.gov. Jama Internal Med. 2013;173(11):972–9. https://doi.org/10.1001/jamainternmed.2013.627
Seeman MV. Clinical trials in psychiatry: do results apply to practice? Can J Psychiatry. 2001;46(4):352–5. https://doi.org/10.1177/070674370104600407
Turner B, Rajeshuni N, Tran EM, Ludwig CA, Tauqeer Z, Weeks B, et al. Characteristics of ophthalmology trials registered in ClinicalTrials.gov, 2007-2018. Am J Ophthalmol. 2020;211:132–41. https://doi.org/10.1016/j.ajo.2019.11.004
Jaffe IS, Chiswell K, Tsalik EL. A decade on: systematic review of ClinicalTrials.gov infectious disease trials, 2007-2017. Open Forum Infect Dis. 2019;6(6). https://doi.org/10.1093/ofid/ofz189
Huang J, He Y, Su Q, Yang J. Characteristics of COVID-19 clinical trials in China based on the registration data on ChiCTR and ClinicalTrials.gov. DDDT. 2020;14:2159–64. https://doi.org/10.2147/dddt.S254354
Zwierzyna M, Davies M, Hingorani AD, Hunter J. Clinical trial design and dissemination: comprehensive analysis of clinicaltrials.gov and PubMed data since 2005. BMJ (Clinical Research ed.). 2018;361:2130. https://doi.org/10.1136/bmj.k2130
Walker I, Newell H. Do molecularly targeted agents in oncology have reduced attrition rates? Nat Rev Drug Discovery. 2009;8(1):15–6. https://doi.org/10.1038/nrd2758
Roberts PJ, Stinchcombe TE, Der CJ, Socinski MA. Personalized medicine in non-small-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy? J Clin Oncol. 2010;28(31):4769–77. https://doi.org/10.1200/jco.2009.27.4365
Peto R, Collins R, Gray R. Large-scale randomized evidence: large, simple trials and overviews of trials. JCE. 1995;48(1):23–40. https://doi.org/10.1016/0895-4356(94)00150-o
Yusuf S, Collins R, Peto R. Why do we need some large, simple randomized trials. Stat Med. 1984;3(4):409–20. https://doi.org/10.1002/sim.4780030421
Lin JY, Lu Y. Establishing a data monitoring committee for clinical trials. Shanghai Arch Psychiatry. 2014;26(1):54–6. https://doi.org/10.3969/j.issn.1002-0829.2014.01.009
We thank Yanhua Xu from Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China for her careful guidance during our writing of this paper.
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