Skip to main content

Advertisement

Log in

Simultaneous Global Drug Development and Multiregional Clinical Trials (MRCT): 5 Years After Implementation of ICH E17 Guidelines

  • Original Research
  • Published:
Therapeutic Innovation & Regulatory Science Aims and scope Submit manuscript

Abstract

The ICH E17 guidelines (2014–2017) on Multiregional Clinical Trials (MRCT) was a joint effort by the regulators and industry to facilitate simultaneous global drug development and registration through taking a strategic approach for clinical trials. In other words, the objective was to reduce the time it takes to bringing medications to patients around the world through minimizing unnecessary duplication of local or regional studies, which may add the regulatory burden to cost and time of bringing new therapies to patients. Under the auspices of ICH, training materials were created and provided to various stakeholders. Despite the successful promotion of the benefits of ICH E17 MRCT guidelines across the different regions, the uptake of some concepts (e.g., pooling strategy) in the ICH E17 guidelines has been slow. This paper describes various factors which could affect the conduct of MRCT at a global level, including ambiguity in definition of “region” (in MRCT), new regulatory requirements to enroll a diverse patient population, the use of decentralized clinical trials, use of data sources other than randomized clinical trials (e.g., use of Real Word Data), and the impact of the COVID-19 pandemic on the conduct of MRCT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1

Similar content being viewed by others

References

  1. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. General principles for planning and design of multi-regional clinical trials E17 https://database.ich.org/sites/default/files/E17EWG_Step4_2017_1116pdf Date: Nov 16, 2017; Date accessed: April 28, 2023.

  2. ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use). 2017. ICH E17 Training Module.

  3. The International Council for Harmonisation of Technical Requirements. for Pharmaceuticals for Human Use Ethnic factors in the acceptability of foreign clinical data E5 (R1). https://database.ich.org/sites/default/files/E5_R1__Guideline.pdf Date: Feb 5, 1998; Date accessed: April 28, 2023.

  4. European Federation of Pharmaceutical Industries and Associations (EFPIA), implementation of the ICH E17 guideline on planning and design of multi-regional clinical trials in international markets. 2021; https://www.efpia.eu/media/636586/efpia-ich-e17-advocacy-toolkit_dec-2021.pdf.

  5. Japan Pharmaceutical Manufacturers Association (JPMA). Drug Evaluation From Now On What’s the value of local data in the global clinical data package? July 2022; https://www.jpma.or.jp/english/reports/drug_evaluation_committee/dsduth00000004zz-att/DS_202212_e17.pdf.

  6. Sohn M, Song Y, Jeon AY, Oh JM, Kim I. Perspectives on adopting the Guideline for multi-regional clinical trials in Korea: a multi-stakeholder survey. Korean J Clin Pharm. 2019;29:267–77.

    Article  Google Scholar 

  7. Asano K, Aoi Y, Kamada S, Uyama Y, Tohkin M. Points to consider for implementation of the ICH E17 Guideline: learning from past multiregional clinical trials in Japan. Clin Pharmacol Ther. 2021;109(6):1555–63. https://doi.org/10.1002/cpt.2121. Epub 2020 Dec 16. PMID: 33245786; PMCID: PMC8246727.

    Article  PubMed  Google Scholar 

  8. Aoi Y, Kato Y, Asano K, Otsubo Y, Uyama Y. Characteristics of Asian participation in multi-regional clinical trials reviewed for drug approval in Japan: opportunities for collaboration between South-East Asia, East Asia, and Japan. Ther Innov Reg Sci; 2023.

  9. Noguchi A, Hanaoka H, Uyama Y. Potential future drug development lag in Japan based on an analysis of multiregional clinical trials in the US, Europe, and East Asia. Ther Innov Reg Sci. 2022;56:523–9.

    Article  Google Scholar 

  10. U.S. Food and Drug Administration. Expedited pathways: Fast track, breakthrough therapy, priority review, accelerated approval. Retrieved from https://www.fda.gov/patients/learn-about-drug-and-device-approvals/fast-track-breakthrough-therapy-accelerated-approval-priority-review Date accessed: October 1, 2023.

  11. European Medicines Agency. PRIME: Priority Medicines. Retrieved from https://www.ema.europa.eu/en/human-regulatory/research-development/prime-priority-medicines Date accessed: October 1, 2023.

  12. Pharmaceuticals and Medical Devices Agency. Further Advancement for Early Patient Access Retrieved from https://www.pmda.go.jp/files/000235784.pdf Date accessed: October 1, 2023.

  13. Fashoyin-Aje L, Beaver JA, Pazdur. R promoting inclusion of members of racial and ethnic minority groups in cancer drug development. JAMA Oncol. 2021;7:1445–6.

    Article  PubMed  Google Scholar 

  14. Desai A, Smith CJ, West HJ. Navigating approval pathways for immunotherapy in NSCLC: should criteria be revised? Nat Rev Clin Oncol. 2023;20:423–4. https://doi.org/10.1038/s41571-023-00761-2.

    Article  PubMed  Google Scholar 

  15. Agarwal P, Sverdlov O, Menon A, Desai A, Smith CJ, West HJ. Navigating approval pathways for immunotherapy in NSCLC: should criteria be revised? Nat Rev Clin Oncol. 2023;20:423–4. https://doi.org/10.1038/s41571-023-00761-2.

    Article  Google Scholar 

  16. Bhatt A, Evans T. (2020). The promise and peril of decentralized trials. Appl Clin Trials, 29(8). https://www.appliedclinicaltrialsonline.com/view/the-promise-and-peril-of-decentralized-trials.

  17. U.S. Food and Drug Administration. (2018). Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: Guidance for Industry and Food and Drug Administration Staff. Retrieved from https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-real-world-evidence-support-regulatory-decision-making-medical-devices Accessed on October 1, 2023.

  18. Purpura CA, Garry EM, Honig N, Case A, Rassen JA. The role of real-world evidence in FDA-Approved New Drug and Biologics license applications. Clin Pharmacol Ther. 2022;111:135–44.

    Article  PubMed  Google Scholar 

  19. Singh R, Teo YY. Asian phenotype underestimates the genetic diversity of Asia yet overstates its Impact on Variability in Drug Disposition and Pharmacodynamics. Clin Pharmacol Ther. 2019;105(4):802–5. https://doi.org/10.1002/cpt.1329.

    Article  PubMed  Google Scholar 

  20. US Congresional Budget Office. (2021), Research and Development in the Pharmaceutical Industry; April 2021, https://www.cbo.gov/publication/57126.

  21. Geilinger U, Leo C, January, HBM New Drug Approval Report (HBM Partners., 2019), p. 16. https://tinyurl.com/yyzze476, (PDF, 1.14 MB).

  22. US Government Accountability Office, Drug Industry. Profits, Research and Development Spending, and Merger and Acquisition deals, GAO-18-40 (November 2017), p. 16, www.gao.gov/products/GAO-18-40./.

  23. IQVIA Institute for Human Data Science. (2019), The Changing Landscape of Research and Development (April 2019), p. 15, https://tinyurl.com/1cm3g2fs.

  24. Salim Y, Wittes J. Interpreting Geographic variations in results of randomized, controlled trials. N Engl J Med. 2016;375(23):2263–71. https://doi.org/10.1056/nejmra1510065.

    Article  Google Scholar 

  25. Li G, Binkowitz B, Wang W, Quan H, Chen J. Simultaneous global New Drug Development Multi-regional clinical trials after ICH E17. Chapman & Hall; 2021.

  26. Ministry of Health, Labour and Welfare, Basic Principles for Conducting Phase I Trials in the Japanese Population Prior to Global Clinical Trials, Administrative Notice on October 27(Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau). 2014. https://www.pmda.go.jp/files/000157777.pdf.

  27. Sharma SK, Kulkarni S, Aggarwal R. COVID-19 Vaccine Development and Launch: a review. Front Public Health. 2021;9:617239. https://doi.org/10.3389/fpubh.2021.617239.

    Article  Google Scholar 

  28. Center for Disease Control. Social Determinants Health CDC. 2021. https://www.cdc.gov/socialdeterminants/index.htm.

  29. FDA. Guidance for Industry: patient-reported outcome measures: use in Medical Product Development to support labeling claims. Silver Spring, MD: US Food and Drug Administration; 2009.

    Google Scholar 

  30. European Medicines Agency Committee for Medicinal Productsfor Human Use. Appendix 2 to the Guideline on the evaluation of Anticancer Medicinal products in Man: the Use of patient-reported outcome (PRO) measures in Oncology studies EMA/CHMP/292464/2014. London, England: European Medicine Agency; 2016.

    Google Scholar 

  31. Chinese Technical. Guidelines for the Implementation of Patient Centered Clinical Trials – DRAFT August 2022.

Download references

Funding

No funding was received for this work.

Author information

Authors and Affiliations

Authors

Contributions

All authors (except JW) were members of the expert working group for ICH E17 guideline published in 2017. The views expressed in this article are those of the authors and do not necessarily reflect the official views of the Pharmaceuticals and Medical Devices Agency, National Medical Products Administration or those of companies that employ them.

Corresponding author

Correspondence to Rominder Singh.

Ethics declarations

Conflict of interest 

RS, WW, AC work for for-profit biopharmaceutical companies.  The work by AC was performed as the Senior Statistical Advisor, Office of the Commissioner, US Food and Drug Administration. JW and YU are regulators who work for their respective regulatory agencies.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Aloka Chakravarty—This work was performed as the Senior Statistical Advisor, Office of the Commissioner, US Food and Drug Administration.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, R., Wang, W., Chakravarty, A. et al. Simultaneous Global Drug Development and Multiregional Clinical Trials (MRCT): 5 Years After Implementation of ICH E17 Guidelines. Ther Innov Regul Sci (2024). https://doi.org/10.1007/s43441-024-00639-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s43441-024-00639-0

Keywords

Navigation