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Chapter 7 - Platform Trials

from Part III - Basic Ingredients for Master Protocols

Published online by Cambridge University Press:  20 March 2023

Jay J. H. Park ,
Edward J. Mills  and
J. Kyle Wathen
By
Jay J. H. Park ,
J. Kyle Wathen  and
Edward J. Mills
Jay J. H. Park
Affiliation:
McMaster University, Ontario
Edward J. Mills
Affiliation:
McMaster University, Ontario
J. Kyle Wathen
Affiliation:
Cytel, Cambridge, Massachusetts
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Summary

In this chapter, we review the concept of platform trials in close detail. Platform trials refer to clinical trials that allow new interventions to be added to the platform over time even, if they are not pre-specified in the design stage. Platform trials can be applied to all phases of clinical trial research. While they are most often conducted as randomised clinical trials with adaptive trial designs (adaptive platform randomised trials), they can be conducted with non-randomised or fixed sample trial designs as well. As a general goal, platform trials aim to establish a shared trial infrastructure where multiple interventions can be evaluated. Independent clinical trial evaluation would result in multiple separate teams creating shorter term infrastructure and trials that would otherwise compete against each other. Platform trials represent an exciting turning point for clinical research. The key design considerations of platform trials are outlined in this chapter.

Keywords

platform trialsMAMSadaptive platform trialsmulti-arm, multi-stage design
Type
Chapter
Information
Introduction to Adaptive Trial Designs and Master Protocols , pp. 73 - 86
Publisher: Cambridge University Press
Print publication year: 2023

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References

Siden, EG, Park, JJ, Zoratti, MJ, et al. Reporting of master protocols towards a standardized approach: a systematic review. Contemp Clin Trials Commun. 2019;15:100406.CrossRefGoogle ScholarPubMed
Park, JJH, Siden, E, Zoratti, MJ, et al. Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols. Trials. 2019;20(1):572.Google Scholar
Vanderbeek, AM, Bliss, JM, Yin, Z, Yap, C. Implementation of platform trials in the COVID-19 pandemic: a rapid review. Contemp Clin Trials. 2022;112:106625.CrossRefGoogle ScholarPubMed
Park, JJ, Mogg, R, Smith, GE, et al. How COVID-19 has fundamentally changed clinical research in global health. Lancet Glob Health. 2021;9(5):e711–e20.CrossRefGoogle ScholarPubMed
Woodcock, J, LaVange, LM. Master protocols to study multiple therapies, multiple diseases, or both. N Eng J Medi. 2017;377(1):62–70.Google Scholar
Berry, SM, Connor, JT, Lewis, RJ. The platform trial: an efficient strategy for evaluating multiple treatments. JAMA. 2015;313(16):1619–20.Google Scholar
Angus, DC, Alexander, BM, Berry, S, et al. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov. 2019;18(10):797–807.Google Scholar
Park, JJH, Detry, MA, Murthy, S, Guyatt, G, Mills, EJ. How to use and interpret the results of a platform trial: users’ guide to the medical literature. JAMA. 2022;327(1):67–74.CrossRefGoogle ScholarPubMed
Thorlund, K, Dron, L, Park, J, Hsu, G, Forrest, JI, Mills, EJ. A real-time dashboard of clinical trials for COVID-19. Lancet Digit Health. 2020;2(6):e286–e7.Google Scholar
Kanters, S, Mills, EJ, Thorlund, K, Bucher, HC, Ioannidis, JP. Antiretroviral therapy for initial human immunodeficiency virus/AIDS treatment: critical appraisal of the evidence from over 100 randomized trials and 400 systematic reviews and meta-analyses. Clin Microbiol Infect. 2014;20(2):114–22.Google Scholar
Parmar, MK, Carpenter, J, Sydes, MR. More multiarm randomised trials of superiority are needed. Lancet. 2014;384(9940):283–4.Google Scholar
Ventz, S, Alexander, BM, Parmigiani, G, Gelber, RD, Trippa, L. Designing clinical trials that accept new arms: an example in metastatic breast cancer. J Clin Oncolo. 2017;35(27):3160–8.Google Scholar
Parmar, MK, Barthel, FM, Sydes, M, et al. Speeding up the evaluation of new agents in cancer. J Natl Cancer Inst. 2008;100(17):1204–14.CrossRefGoogle ScholarPubMed
Sydes, MR, Parmar, MKB, James, ND, et al. Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial. Trials. 2009;10:39.Google Scholar
Parmar, MK, Sydes, MR, Cafferty, FH, et al. Testing many treatments within a single protocol over 10 years at MRC Clinical Trials Unit at UCL: multi-arm, multi-stage platform, umbrella and basket protocols. Clin Trials. 2017;14(5):451–61.Google Scholar
Mills, EJ, Thorlund, K, Ioannidis, JP. Demystifying trial networks and network meta-analysis. BMJ. 2013;346:f2914.Google Scholar
Park, JJH, Harari, O, Dron, L, et al. An overview of platform trials with a checklist for clinical readers. J Clin Epidemiol. 2020;125:1–8.CrossRefGoogle ScholarPubMed
Angus, DC, Derde, L, Al-Beidh, F, et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: the REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020;324(13):1317–29.Google Scholar
Recovery Collaborative Group, Horby, P, Lim, WS, Emberson, JR, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704.Google Scholar
Park, JJH, Mogg, R, Smith, GE, et al. How COVID-19 has fundamentally changed clinical research in global health. Lancet Glob Health. 2021;9(5):e711–e20.CrossRefGoogle ScholarPubMed
Bugin, K, Woodcock, J. Trends in COVID-19 therapeutic clinical trials. Nat Rev Drug Discov. 2021;20(4):254–5.Google Scholar
Recovery Collaborative Group, Horby, P, Lim, WS, Emberson, JR, et al. Dexamethasone in hospitalized patients with Covid-19 – preliminary report. N Engl J Med. 2020;384(8):693–704.Google Scholar
Beigel, JH, Tomashek, KM, Dodd, LE, et al. Remdesivir for the treatment of Covid-19 – final report. N Engl J Med. 2020;383:1813–26.CrossRefGoogle ScholarPubMed
Writing Committee for the Remap-CAP Investigators, Angus, DC, Derde, L, Al-Beidh, F, et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: the REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020;324(13):1317–29.Google Scholar
Angus, DC, Berry, S, Lewis, RJ, et al. The Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia (REMAP-CAP) study: rationale and design. Ann Am Thorac Soc. 2020;17(7):879–91.CrossRefGoogle ScholarPubMed
Reis, G, Moreira Silva, E, Medeiros Silva, DC, et al. Effect of early treatment with hydroxychloroquine or lopinavir and ritonavir on risk of hospitalization among patients with COVID-19: the TOGETHER Randomized Clinical Trial. JAMA Netw Open. 2021;4(4):e216468.Google Scholar
Group PTC. Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 2021;397(10279):1063–74.Google Scholar
Park, JJH, Dron, L, Mills, EJ. Moving forward in clinical research with master protocols. Contemp Clin Trials. 2021;106:106438.Google Scholar
Saville, BR, Berry, SM. Efficiencies of platform clinical trials: a vision of the future. Clin Trials. 2016;13(3):358–66.Google Scholar
Adaptive Platform Trials C. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov. 2019;18(10):797–807.Google Scholar
Hummel, J, Wang, S, Kirkpatrick, J. Using simulation to optimize adaptive trial designs: applications in learning and confirmatory phase trials. Clin Invest. 2015;5(4):401–13.Google Scholar
Viele, K, McGlothlin, A, Broglio, K. Interpretation of clinical trials that stopped early. Jama. 2016;315(15):1646–7.CrossRefGoogle ScholarPubMed
Park, JJ, Thorlund, K, Mills, EJ. Critical concepts in adaptive clinical trials. Clin Epidemiol. 2018;10:343–51.Google Scholar
Biswas, A, Bhattacharya, R. Response-adaptive designs for continuous treatment responses in phase III clinical trials: a review. Stat Methods Med Res. 2016;25(1):81–100.Google Scholar
U.S. Department of Health and Human Services, Food and Drug Administration. Adaptive Designs for Clinical Trials of Drugs and Biologics Guidance for Industry. U.S. Department of Health and Human Services; 2019.Google Scholar
Thorlund, K, Haggstrom, J, Park, JJ, Mills, EJ. Key design considerations for adaptive clinical trials: a primer for clinicians. BMJ. 2018;360:k698.Google Scholar
Park, JJH, Hsu, G, Siden, EG, Thorlund, K, Mills, EJ. An overview of precision oncology basket and umbrella trials for clinicians. CA Cancer J Clin. 2020;70(2):125–37.Google Scholar
Little, RJ, Lewis, RJ. Estimands, estimators, and estimates. JAMA. 2021;326(10):967–8.Google Scholar
Collignon, O, Schiel, A, Burman, CF, et al. Estimands and complex innovative designs. Clin Pharmacol Ther. 2022. Online ahead of print.Google Scholar
Prentice, RL. Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med. 1989;8(4):431–40.Google Scholar
Haslam, A, Hey, SP, Gill, J, Prasad, V. A systematic review of trial-level meta-analyses measuring the strength of association between surrogate end-points and overall survival in oncology. Eur J Cancer. 2019;106:196–211.Google Scholar
Prasad, V, Kim, C, Burotto, M, Vandross, A. The strength of association between surrogate end points and survival in oncology: a systematic review of trial-level meta-analyses. JAMA Intern Med. 2015;175(8):1389–98.CrossRefGoogle ScholarPubMed
Beauchemin, C, Johnston, JB, Lapierre, ME, Aissa, F, Lachaine, J. Relationship between progression-free survival and overall survival in chronic lymphocytic leukemia: a literature-based analysis. Curr Oncol (Toronto, Ont). 2015;22(3):e148–56.Google Scholar
Cortazar, P, Zhang, JJ, Sridhara, R, Justice, RL, Pazdur, R. Relationship between OS and PFS in metastatic breast cancer (MBC): review of FDA submission data. J Clin Oncol. 2011;29(15_suppl):1035.Google Scholar
Gyawali, B, Hey, SP, Kesselheim, AS. A Comparison of response patterns for progression-free survival and overall survival following treatment for cancer with PD-1 inhibitors: a meta-analysis of correlation and differences in effect sizes. JAMA Netw Open. 2018;1(2):e180416–e.Google Scholar
Berry, DA. Bayesian clinical trials. Nat Rev Drug Discov. 2006;5(1):27–36.CrossRefGoogle ScholarPubMed
Saville, BR, Connor, JT, Ayers, GD, Alvarez, J. The utility of Bayesian predictive probabilities for interim monitoring of clinical trials. Clin Trials. 2014;11(4):485–93.Google Scholar
Lachin, JM. A review of methods for futility stopping based on conditional power. Stat Med. 2005;24(18):2747–64.CrossRefGoogle ScholarPubMed
Thorlund, K, Golchi, S, Haggstrom, J, Mills, E. Highly Efficient Clinical Trials Simulator (HECT): software application for planning and simulating platform adaptive trials. Gates Open Res. 2019;3:780.CrossRefGoogle ScholarPubMed
Thorlund, K, Golchi, S, Mills, E. Bayesian adaptive clinical trials of combination treatments. Contemp Clin Trials Commun. 2017;8:227–33.Google Scholar
Schiavone, F, Bathia, R, Letchemanan, K, et al. This is a platform alteration: a trial management perspective on the operational aspects of adaptive and platform and umbrella protocols. Trials. 2019;20(1):264.Google Scholar
Hague, D, Townsend, S, Masters, L, et al. Changing platforms without stopping the train: experiences of data management and data management systems when adapting platform protocols by adding and closing comparisons. Trials. 2019;20(1):294.Google Scholar
Dunnett, CW. A multiple comparison procedure for comparing several treatments with a control. JASA. 1955;50(272):1096–121.Google Scholar
Berry, SM, Petzold, EA, Dull, P, et al. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: a model for pandemic response. Clin Trials. 2016;13(1):22–30.CrossRefGoogle Scholar
Sydes, MR, Parmar, MKB, Mason, MD, et al. Flexible trial design in practice – stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial. Trials. 2012;13:168.Google Scholar
Barker, AD, Sigman, CC, Kelloff, GJ, et al. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther. 2009;86(1):97–100.Google Scholar
Committee for Proprietary Medicinal Products. ICH Topic E 10: Choice of Control Group in Clinical Trials., p. 30. European Medicines Agency (EMEA); 2001;Google Scholar
Thorlund, K, Dron, L, Park, JJH, Mills, EJ. Synthetic and external controls in clinical trials – a primer for researchers. Clin Epidemiol. 2020;12:457–67.Google Scholar
Lee, KM, Wason, J. Including non-concurrent control patients in the analysis of platform trials: is it worth it? BMC Med Res Methodol. 2020;20(1):165.Google Scholar
Berry, SM, Reese, CS, Larkey, PD. Bridging different eras in sports. JASA 1999;94(447):661–76.Google Scholar
Viele, K, Berry, S, Neuenschwander, B, et al. Use of historical control data for assessing treatment effects in clinical trials. Pharm Stat. 2014;13(1):41–54.CrossRefGoogle ScholarPubMed
Dron, L, Golchi, S, Hsu, G, Thorlund, K. Minimizing control group allocation in randomized trials using dynamic borrowing of external control data – an application to second line therapy for non-small cell lung cancer. Contemp Clin Trials Commun. 2019;16:100446.Google Scholar
Yu, LM, Bafadhel, M, Dorward, J, et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 2021;398(10303):843–55.CrossRefGoogle ScholarPubMed

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