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Oncology and Therapy

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Open Access 08-12-2023 | Original Research

Diversity in Oncology Clinical Trials: Current Landscape for Industry-Sponsored Clinical Trials in Asia

Authors: Dany Habr, Manmohan Singh, Roberto Uehara

Published in: Oncology and Therapy | Issue 1/2024

Abstract

Introduction

There has been a growing recognition on the importance of diversity in clinical trials. Existing research has highlighted a significant demographic imbalance. Amidst this renewed focus on diversity, it is crucial to acknowledge that Asia comprises over half of the world’s population. Given the region’s demographic significance, we sought to compare various characteristics and growth rates for trials with sites in Asia against those without any sites in Asia.

Methods

We performed comprehensive analyses of industry-sponsored phase 2 and 3 oncology trials registered at Clinicaltrials.gov, using drugs or biologics as investigational agents and executed between 1 January 2018 and 31 December 2022. We applied the compound annual growth rate (CAGR) as an analytical tool to track the trial growth rates over this 5-year period.

Results

We identified 894 industry-sponsored phase 2 and 3 cancer studies with available study location data. Out of these, 415 trials (46.42%) had study sites in Asia. Notably, these trials with sites in Asia were also more likely to be phase 3 trials (39.76% vs 6.47%, p < 0.001), include female and paediatric populations, and be randomised trials. Interestingly, lung and stomach cancers were more commonly studied in these trials, while myeloma was less commonly studied. The number of trial sites for liver cancer was not significantly higher for Asia, even though the incidence of the disease is much higher in this region. Despite an overall declining trend in the number of clinical trials in the last 5 years, we observed a transitional positive increase in the CAGR from 2020 to 2021 for trials with sites in Asia. However, East Asia, specifically China, exhibited a disproportionate overrepresentation in these trials.

Conclusions

There are notable characteristics of clinical trials with sites in Asia. Comprehending these disparities may aid in the strategic planning to enhance a balanced representation of ethnicities in trials.

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Spreafico A, Hansen AR, Abdul Razak AR, Bedard PL, Siu LL. The future of clinical trial design in oncology. Cancer Discov. 2021;11(4):822–37. https://doi.org/10.1158/2159-8290.Cd-20-1301. (PMID: 33811119).CrossRefPubMedPubMedCentral

Ahuja AS. Should RCT’s be used as the gold standard for evidence based medicine? Integr Med Res. 2019;8(1):31–2. https://doi.org/10.1016/j.imr.2019.01.001. (PMID: 30805294).CrossRefPubMedPubMedCentral

Umscheid CA, Margolis DJ, Grossman CE. Key concepts of clinical trials: a narrative review. Postgrad Med. 2011;123(5):194–204. https://doi.org/10.3810/pgm.2011.09.2475. (PMID: 21904102).CrossRefPubMedPubMedCentral

Food and Drug Administration. 2015–2019 Drug trials snapshots summary report. Five-Year summary and analysis of clinical trial participation and demographics. [updated November 2020; cited 2023 May 14]. Available from https://www.fda.gov/media/143592/download.

Schwartz AL, Alsan M, Morris AA, Halpern SD. Why diverse clinical trial participation matters. N Engl J Med. 2023;388(14):1252–4. https://doi.org/10.1056/NEJMp2215609.CrossRefPubMed

Habr D, McRoy L, Papadimitrakopoulou VA. Age is just a number: considerations for older adults in cancer clinical trials. J Natl Cancer Inst. 2021;113(11):1460–4. https://doi.org/10.1093/jnci/djab070. (PMID: 33881547).CrossRefPubMedPubMedCentral

Habr D, Corsaro M. Reimagining diversity in multiple myeloma clinical trials. Hematol Oncol. 2022;40(4):689–94. https://doi.org/10.1002/hon.2997.CrossRefPubMedPubMedCentral

Sadigov R. Rapid growth of the world population and its socioeconomic results. Sci World J. 2022;2022:8110229. https://doi.org/10.1155/2022/8110229. (PMID: 35370481).CrossRef

Niles PM, Jun J, Lor M, Ma C, Sadarangani T, Thompson R, et al. Honoring Asian diversity by collecting Asian subpopulation data in health research. Res Nurs Health. 2022;45(3):265–9. https://doi.org/10.1002/nur.22229. (PMID: 35462441).CrossRefPubMedPubMedCentral

10.

Nguyen HT, Zheng A, Gugel A, Kistin CJ. Asians and Asian subgroups are underrepresented in medical research studies published in high-impact generalist journals. J Immigr Minor Health. 2021;23(3):646–9. https://doi.org/10.1007/s10903-021-01142-6. (PMID: 33515160).CrossRefPubMedPubMedCentral

11.

Kahn JM, Gray DM 2nd, Oliveri JM, Washington CM, DeGraffinreid CR, Paskett ED. Strategies to improve diversity, equity, and inclusion in clinical trials. Cancer. 2022;128(2):216–21. https://doi.org/10.1002/cncr.33905. (PMID: 34495551).CrossRefPubMed

12.

Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. Meta-analysis group in cancer. J Clin Oncol. 1998;16(11):3537–41. https://doi.org/10.1200/JCO.1998.16.11.3537.

13.

Landgren O, Gridley G, Turesson I, Caporaso NE, Goldin LR, Baris D, et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood. 2006;107(3):904–6. https://doi.org/10.1182/blood-2005-08-3449. (PMID: 16210333).CrossRefPubMedPubMedCentral

14.

Food and Drug Administration. FDA takes important steps to increase racial and ethnic diversity in clinical trials [cited 2023 May 27]. Available from https://www.fda.gov/news-events/press-announcements/fda-takes-important-steps-increase-racial-and-ethnic-diversity-clinical-trials.

15.

Verma R, Khanna P, Chawla S. Vaccines for the elderly need to be introduced into the immunization program in India. Hum Vaccin Immunother. 2014;10(8):2468–70. https://doi.org/10.4161/hv.29254. (PMID: 25424957).CrossRefPubMedPubMedCentral

16.

Atal I, Trinquart L, Porcher R, Ravaud P. Differential globalization of industry- and non-industry-sponsored clinical trials. PLoS One. 2015;10(12): e0145122. https://doi.org/10.1371/journal.pone.0145122. (PMID: 26658791).CrossRefPubMedPubMedCentral

17.

Dosi G, Palagi E, Roventini A, Russo E. Do patents really foster innovation in the pharmaceutical sector? Results from an evolutionary, agent-based model. J Econ Behav Organ. 2023;212:564–89. https://doi.org/10.1016/j.jebo.2023.05.039.CrossRef

18.

Doi M, Yukawa K, Sato H. Characteristics of Asian 4 countries on cancer clinical trials registered in the International Clinical Trials Registry Platform between 2005 and 2018. Chin Clin Oncol. 2021;10(3):28. https://doi.org/10.21037/cco-21-17. (PMID: 34182763).CrossRefPubMed

19.

U.S. National Library of Medicine. ClinicalTrials.gov. Available from https://clinicaltrials.gov/.

20.

U.S. National Library of Medicine. FDAAA 801 and the final rule [cited 2023 May 11]. Available from https://clinicaltrials.gov/ct2/manage-recs/fdaaa#WhichTrialsMustBeRegistered.

21.

De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. Lancet. 2004;364(9438):911–2. https://doi.org/10.1016/s0140-6736(04)17034-7. (PMID: 15364170).CrossRefPubMed

22.

World Health Organization. International clinical trials registry platform—search portal [cited 2023 May 11]. Available from https://trialsearch.who.int/.

23.

Zarin DA, Fain KM, Dobbins HD, Tse T, Williams RJ. 10-Year update on study results submitted to ClinicalTrials.gov. N Engl J Med. 2019;381(20):1966–74. https://doi.org/10.1056/NEJMsr1907644. (PMID: 31722160).CrossRefPubMedPubMedCentral

24.

Rajappa S, Singh M, Uehara R, Schachterle SE, Setia S. Cancer incidence and mortality trends in Asia based on regions and human development index levels: an analyses from GLOBOCAN 2020. Curr Med Res Opin. 2023;39(8):1127–37. https://doi.org/10.1080/03007995.2023.2231761. (PMID: 37395248).CrossRefPubMed

25.

Jemielita T, Tse A, Chen C. Oncology phase II proof-of-concept studies with multiple targets: randomized controlled trial or single arm? Pharm Stat. 2020;19(2):117–25. https://doi.org/10.1002/pst.1972. (PMID: 31424631).CrossRefPubMed

26.

Buyse M. Phase III design: principles. Chin Clin Oncol. 2016;5(1):10. https://doi.org/10.3978/j.issn.2304-3865.2014.08.05. (PMID: 26932434).MathSciNetCrossRefPubMed

27.

Dillman RO, Koziol JA. Phase I cancer trials: limitations and implications. Mol Biother. 1992;4(3):117–21 (PMID: 1445664).PubMed

28.

Jung SH. Phase II cancer clinical trials for biomarker-guided treatments. J Biopharm Stat. 2018;28(2):256–63. https://doi.org/10.1080/10543406.2017.1372777. (PMID: 28902567).CrossRefPubMed

29.

Jung SH. Design and analysis of cancer clinical trials for personalized medicine. J Pers Med. 2021;11(5):376. https://doi.org/10.3390/jpm11050376. (PMID: 34064394).CrossRefPubMedPubMedCentral

30.

World Health Organization—International Agency for Research on Cancer. Data & methods [cited 2023 May 14]. Available from https://gco.iarc.fr/today/data-sources-methods.

31.

National Library of Medicine. MeSH. Neoplasms [cited 2023 March 27]. Available from https://www.ncbi.nlm.nih.gov/mesh/68009369.

32.

Habr D, Ferdinand R. Addressing racial/ethnic disparities in cancer clinical trials: everyone has a role to play. Cancer. 2021;127(18):3282–9. https://doi.org/10.1002/cncr.33600.CrossRefPubMed

33.

Fountzilas E, Tsimberidou AM, Vo HH, Kurzrock R. Clinical trial design in the era of precision medicine. Genome Med. 2022;14(1):101. https://doi.org/10.1186/s13073-022-01102-1.CrossRefPubMedPubMedCentral

34.

Murthy S, Mandl KD, Bourgeois FT. Industry-sponsored clinical research outside high-income countries: an empirical analysis of registered clinical trials from 2006 to 2013. Health Res Policy Syst. 2015;13:28. https://doi.org/10.1186/s12961-015-0019-6. (PMID: 26041551).CrossRefPubMedPubMedCentral

35.

Why diverse representation in clinical research matters and the current state of representation within the clinical research ecosystem. In: Bibbins-Domingo K, Helman A, editors. Improving representation in clinical trials and research: building research equity for women and underrepresented groups. Washington DC: National Academies Press (US); 2022.

36.

Washington V, Franklin JB, Huang ES, Mega JL, Abernethy AP. Diversity, equity, and inclusion in clinical research: a path toward precision health for everyone. Clin Pharmacol Ther. 2023;113(3):575–84. https://doi.org/10.1002/cpt.2804.CrossRefPubMed

37.

Zhou W, Christiani DC. East meets west: ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians. Chin J Cancer. 2011;30(5):287–92. https://doi.org/10.5732/cjc.011.10106. (PMID: 21527061).CrossRefPubMedPubMedCentral

38.

Kanapuru B, Fernandes LL, Fashoyin-Aje LA, Baines AC, Bhatnagar V, Ershler R, et al. Analysis of racial and ethnic disparities in multiple myeloma US FDA drug approval trials. Blood Adv. 2022;6(6):1684–91. https://doi.org/10.1182/bloodadvances.2021005482. (PMID: 35114691).CrossRefPubMedPubMedCentral

39.

Liu Y, Liu L. Changes in the epidemiology of hepatocellular carcinoma in Asia. Cancers (Basel). 2022;14(18):4473. https://doi.org/10.3390/cancers14184473. (PMID: 36139633).CrossRefPubMed

40.

Miyazaki K, Sato Y, Hanaoka H, Uyama Y. Current status and open issues concerning global clinical trials (GCTs) in Japan and East Asia. Clin Transl Sci. 2017;10(6):503–8. https://doi.org/10.1111/cts.12485. (PMID: 28675655).CrossRefPubMedPubMedCentral

41.

Ali S, Egunsola O, Babar ZUD, Hasan SS. Clinical trials in Asia: a World Health Organization database study. Perspect Clin Res. 2019;10(3):121–4. https://doi.org/10.4103/picr.PICR_109_18. (PMID: 31404203).CrossRefPubMedPubMedCentral

42.

Upadhaya S, Yu JX, Oliva C, Hooton M, Hodge J, Hubbard-Lucey VM. Impact of COVID-19 on oncology clinical trials. Nat Rev Drug Discov. 2020;19(6):376–7.CrossRefPubMed

43.

Sathian B, Asim M, Banerjee I, Pizarro AB, Roy B, van Teijlingen ER, et al. Impact of COVID-19 on clinical trials and clinical research: a systematic review. Nepal J Epidemiol. 2020;10(3):878–87. https://doi.org/10.3126/nje.v10i3.31622. (PMID: 33042591).CrossRefPubMedPubMedCentral

44.

Tang W, Huang Y, Zhou D, Huang Y, Chen Y, Ren S, et al. Evolving drug regulatory landscape in China: a clinical pharmacology perspective. Clin Transl Sci. 2021;14(4):1222–30. https://doi.org/10.1111/cts.12987.CrossRefPubMedPubMedCentral

45.

Ge Q, Xu L, DiMasi JA, Kaitin KI, Shao L. Impact of regulatory system changes on the availability of innovative drugs in China. Nat Rev Drug Discov. 2023;22(5):344–5. https://doi.org/10.1038/d41573-023-00058-0. (PMID: 37059845).CrossRefPubMed

46.

Hata T, Nakamura K, Yonemori K, Noguchi E, Watanabe M, Sohn J, et al. Regulatory and operational challenges in conducting Asian international academic trial for expanding the indications of cancer drugs. Clin Transl Sci. 2021;14(3):1015–25. https://doi.org/10.1111/cts.12965.CrossRefPubMedPubMedCentral

47.

Rajman I, Hirano M, Honma W, Zhao S. New paradigm for expediting drug development in Asia. Drug Discov Today. 2020;25(3):491–6. https://doi.org/10.1016/j.drudis.2019.12.013.CrossRefPubMed

48.

Nephew LD. Accountability in clinical trial diversity: The buck stops where? EClin Med. 2021;36:100906. https://doi.org/10.1016/j.eclinm.2021.100906. (PMID: 34041464).CrossRef

49.

Food and Drug Administration. Diversity plans to improve enrollment of participants from underrepresented racial and ethnic populations in clinical trials guidance for industry (draft guidance). Apr 2022 [cited 2023 May 10]. Available from https://www.fda.gov/media/157635/download

50.

Voon P-J, Lai W-H, Bustaman RS, Siu LL, Razak ARA, Yusof A, et al. Early phase oncology clinical trials in Malaysia: current status and future perspectives. Asia Pac J Clin Oncol. 2023;19(3):296–304. https://doi.org/10.1111/ajco.13886.CrossRefPubMed

51.

Eala MAB, Basilio PAS, Dee EC, Cereno REP, Ang CD, Magsanoc NJ, et al. Cancer clinical trials in the Philippines. Cancer Causes Control. 2022;33(10):1273–5. https://doi.org/10.1007/s10552-022-01611-9.CrossRefPubMed

52.

Ooi A, Khalid K. Establishing early phase capabilities in Malaysia. Applied Clinical Trials. 2019;28(11):10–6.

53.

Lam WK, White NW, Chan-Yeung MM. Lung cancer epidemiology and risk factors in Asia and Africa. Int J Tuberc Lung Dis. 2004;8(9):1045–57 (PMID: 15455588).PubMed

54.

Wong N, Chan KY, Macgregor PF, Lai PB, Squire JA, Beheshti B, et al. Transcriptional profiling identifies gene expression changes associated with IFN-alpha tolerance in hepatitis C-related hepatocellular carcinoma cells. Clin Cancer Res. 2005;11(3):1319–26 (PMID: 15709204).CrossRefPubMed

55.

Yathindranath S, Kureishi A, Singh S, Yeow S, Geng G, Wai K, et al. Evolution of the clinical trial landscape in Asia Pacific. Open Access J Clin Trials. 2014;6:75–84.

56.

Sonoda M, Urbiztondo MRU, Siburian MD, Kerdsakundee N, Muchanga SMJ, Iiyama T. Boosting multiregional clinical trials (MRCT) in Asia through the establishment of the Japan-led network for clinical research, the ARO alliance for ASEAN & East Asia (ARISE). Glob Health Med. 2022;4(4):247–9. https://doi.org/10.35772/ghm.2022.01007. (PMID: 36119781).CrossRefPubMedPubMedCentral

57.

Esteban D, Laudico A, Uy N, Benabay L. Cancer registration in the Philippines. Asian Pac J Cancer Prev. 2001;2:55–60.

58.

Ghersi D, Pang T. En route to international clinical trial transparency. Lancet. 2008;372(9649):1531–2. https://doi.org/10.1016/s0140-6736(08)61635-9. (PMID: 18984176).CrossRefPubMed

59.

Habr D, Wolf Gianares B, Schuler KW, Chari D. Patients at the heart of the scientific dialogue: an industry perspective. Oncol Ther. 2023;11(1):15–24. https://doi.org/10.1007/s40487-023-00220-z. (PMID: 36705813).CrossRefPubMedPubMedCentral

60.

The Pfizer corporate affairs multicultural center of excellence a catalyst for change [cited 2023 May 27]. Available from https://pfe-pfizercom-prod.s3.amazonaws.com/health/Pfizer_MCoE_One_Pager.pdf.

61.

American Cancer Society. The American Cancer Society and Pfizer launch community grants focused on addressing systemic race-related barriers that contribute to disparities in care among black men and women with cancer. Nov 17, 2020 [cited 2023 May 27]. Available from http://pressroom.cancer.org/2020-11-17-The-American-Cancer-Society-and-Pfizer-Launch-Community-Grants-Focused-on-Addressing-Systemic-Race-Related-Barriers-that-Contribute-to-Disparities-in-care-Among-Black-Men-and-Women-with-Cancer.

62.

Columbia University. Columbia University and Pfizer to establish clinical trials diversity initiative. Sep 09, 2021 [cited 2023 May 27]. Available from https://www.cuimc.columbia.edu/news/columbia-university-and-pfizer-establish-clinical-trials-diversity-initiative.

Title: Diversity in Oncology Clinical Trials: Current Landscape for Industry-Sponsored Clinical Trials in Asia
Authors: Dany Habr
Manmohan Singh
Roberto Uehara
Publication date: 08-12-2023
Publisher: Springer Healthcare
Published in: Oncology and Therapy / Issue 1/2024
Print ISSN: 2366-1070
Electronic ISSN: 2366-1089
DOI: https://doi.org/10.1007/s40487-023-00254-3

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