Figure 5. Regulatory support (in terms of pre-consultation meetings) provided by regulatory agencies in selected countries.
The lack of a reference could create difficulties for sponsors seeking to conduct innovative clinical trials for possible approval. It is therefore imperative to have an individual consultation session to obtain an alignment with the authorities on their expectations when filing an application for regulatory approval.
3. Relative novelty and risk of ICTD
To date, little is known about the use of ICTDs for cell and gene therapy products – in the case of adaptive trials, there is a lack of clarity on when they are applicable, what they can or cannot accomplish, what their practical implications are and how their results should be interpreted or reported5. Studies using real-world data to provide information about a broader patient population may contain inherent biases in their data sources that could limit their value in establishing causality between drug exposure and outcomes.20.
Despite the potential benefits that ICTDs can bring to CGTPs, developers should still exercise due diligence when considering the suitability of this mode of test design for their IMPs. To maximize their chances of success in market access, it is recommended that industry players strive to understand and apply the recommendations of regulatory agencies, as well as partner with providers with a clinical trial experience for a better understanding of the ICTD landscape.
CGTPS offers hope for the treatment of serious illnesses with unmet medical needs – expertise is needed to navigate the regulatory space to ensure regulatory compliance and access to every market. To learn more about cell and gene therapy products in the JAPAC region, please click here.
- Iglesias-Lopez, C., Agustí, A., Vallano, A., & Obach, M. (2021). Current Landscape of Clinical Development and Approval of Advanced Therapies. Molecular therapy – Methods and clinical development, 23, 606–618. https://doi.org/10.1016/j.omtm.2021.11.003
- Galli, MC and Serabian, M. (2015). Regulatory aspects of cell and gene therapy products. Advances in experimental medicine and biology. Volume 871. https://www.royanatmp.com/pdf/Regulatory-Aspects-of-Gene-Therapy-and-Cell-Therapy-Products.pdf
- Friedman FL, Furberg CD, DeMets DL. Fundamentals of Clinical Trials, 4th ed. New York: Springer; 2010.
- Evans, CH, Ildstad, ST, and Institute of Medicine (USA) (Eds.). (2001). Small clinical trials: issues and challenges. National Academy Press.
- Pallmann, P., Bedding, AW, Choodari-Oskooei, B., Dimairo, M., Flight, L., Hampson, LV, Holmes, J., Mander, AP, Odondi, L., Sydes, MR, Villar, SS, Wason, JMS, Weir, CJ, Wheeler, GM, Yap, C., & Jaki, T. (2018). Adaptive Designs in Clinical Trials: Why Use Them, and How to Perform and Report Them. BMC Medicine, 16(1), 29. https://doi.org/10.1186/s12916-018-1017-7
- Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER). (2021). Study of several versions of a cell or gene therapy product in an early phase clinical trial: draft guidance for industry. Investigate multiple versions of a cell or gene therapy product in an early phase clinical trial; Draft Industry Guidance (fda.gov)
- Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER). (2020). Interacting with the FDA on Complex and Innovative Trial Designs for Drugs and Biologics: Guidance for Industry. https://www.fda.gov/media/130897/download
- An Introduction and Overview of Innovative Trial Design | nhlbi, nih. (nd). https://www.nhlbi.nih.gov/events/2018/introduction-and-overview-innovative-trial-design
- Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER). (2019). Adaptive Designs for Clinical Trials of Drugs and Biologics: Guidance for Industry. https://www.fda.gov/media/78495/download
- Mahajan, R., & Gupta, K. (2010). Clinical trials in adaptive design: Methodology, issues and perspectives. Indian Journal of Pharmacology, 42(4), 201–207. https://doi.org/10.4103/0253-7613.68417
- Yap C, Billingham LJ, Cheung YK, Craddock C, O’Quigley J. Dose transition pathways: the missing link between complex dose-finding designs and simple decision-making. Clin Cancer Res. 2017;23:7440–7.
- Naas, LA (2019). Design of clinical trials: basket and umbrella studies. Lilly essays. https://trials.lilly.com/en-US/blog/clinical-trial-design-basket-umbrella-studies
- FOCUS4: A landmark trial in colorectal cancer—Department of Oncology. (nd). https://www.oncology.ox.ac.uk/blog/focus4-a-flagship-trial-in-colorectal-cancer
- ISPOR Glasgow. (2017). Innovative clinical trial designs: welcomed by regulators, but what about payers? https://www.ispor.org/docs/default-source/presentations/1330.pdf?sfvrsn=56ed4398_1
- Hassan, A., Booth, C., Brightwell, A., Allwood, Z., Veys, P., Rao, K., Hönig, M., Friedrich, W., Gennery, A., Slatter, M., Bredius, R., Finocchi, A., Cancrini, C., Aiuti, A., Porta, F., Lanfranchi, A., Ridella, M., Steward, C., Filipovich, A., … Gaspar, HB ( 2012). Outcome of hematopoietic stem cell transplantation for severe combined immune deficiency deficient in adenosine deaminase. Blood, 120(17), 3615–3624. https://doi.org/10.1182/blood-2011-12-396879
- Lu, C. (Cindy), Li, X. (Nicole), Broglio, K., Bycott, P., Jiang, Q., Li, X., McGlothlin, A., Tian, H. and Ye, J. (2021). Practical Considerations and Recommendations for the Core Protocol Framework: Basket, Umbrella, and Platform Trials. Therapeutic Innovation and Regulatory Science, 55(6), 1145–1154. https://doi.org/10.1007/s43441-021-00315-7
- Devine, C. (2020). Operationalization of the design of complex innovative assays (new approach from the FDA). Medical space. https://www.medpace.com/operationalizing-complex-innovative-trial-design-fdas-new-approach/
- CID case study: a study in patients with systemic lupus erythematosus. (nd). https://www.fda.gov/media/155404/download
- Clinical trials: how technology is driving digitization (nd). Cambridge Consultants. https://www.cambridgeconsultants.com/sites/default/files/uploaded-pdfs/Clinical%20trials%20-%20how%20technology%20is%20driving%20digitization_1.pdf
- Ghadessi, M., Tang, R., Zhou, J., Liu, R., Wang, C., Toyoizumi, K., Mei, C., Zhang, L., Deng, CQ and Beckman, RA (2020) . A roadmap for the use of historical controls in clinical trials – by the Drug Information Association Adaptive Design Scientific Working Group (Dia-adswg). Orphanet Journal of Rare Diseases15(1), 69. https://doi.org/10.1186/s13023-020-1332-x