Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-05-27T17:01:57.547Z Has data issue: false hasContentIssue false

Part V - A Practical Guide to Adaptive Trial Designs and Master Protocols

Published online by Cambridge University Press:  20 March 2023

Jay J. H. Park
Affiliation:
McMaster University, Ontario
Edward J. Mills
Affiliation:
McMaster University, Ontario
J. Kyle Wathen
Affiliation:
Cytel, Cambridge, Massachusetts
Get access

Summary

Image of the first page of this content. For PDF version, please use the ‘Save PDF’ preceeding this image.'
Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

Mueller, PS, Montori, VM, Bassler, D, Koenig, BA, Guyatt, GH. Ethical issues in stopping randomized trials early because of apparent benefit. Ann Int Med. 2007;146(12):878–81.CrossRefGoogle ScholarPubMed
Guyatt, GH, Briel, M, Glasziou, P, Bassler, D, Montori, VM. Problems of stopping trials early. BMJ. 2012;344:e3863.Google Scholar
Bassler, D, Montori, VM, Briel, M, Glasziou, P, Guyatt, G. Early stopping of randomized clinical trials for overt efficacy is problematic. J Clin Epidemiol. 2008;61(3):241–6.CrossRefGoogle ScholarPubMed
Briel, M, Bassler, D, Wang, AT, Guyatt, GH, Montori, VM. The dangers of stopping a trial too early. J Bone Joint Surg Am. 2012;94(Suppl 1):5660.CrossRefGoogle ScholarPubMed
Pocock, SJ, Hughes, MD. Practical problems in interim analyses, with particular regard to estimation. Control Clin Trials. 1989;10(4 Suppl):209S–21S.CrossRefGoogle ScholarPubMed
Fan, XF, DeMets, DL, Lan, KK. Conditional bias of point estimates following a group sequential test. J Biopharm Stat. 2004;14(2):505–30.Google Scholar
Goodman, SN. Stopping at nothing? Some dilemmas of data monitoring in clinical trials. Ann Int Med. 2007;146(12):882–7.Google Scholar
Viele, K, McGlothlin, A, Broglio, K. Interpretation of clinical trials that stopped early. Jama. 2016;315(15):1646–7.CrossRefGoogle ScholarPubMed
Flight, L, Julious, S, Brennan, A, Todd, S. Expected value of sample information to guide the design of group sequential clinical trials. Med Decis Making. 2022;42(4):461–73.CrossRefGoogle ScholarPubMed
Dimairo, M, Boote, J, Julious, SA, Nicholl, JP, Todd, S. Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials. Trials. 2015;16(1):116.Google Scholar
Jaki, T. Uptake of novel statistical methods for early-phase clinical studies in the UK public sector. Clin Trials. 2013;10(2):344–6.Google Scholar
Madani Kia, T, Marshall, JC, Murthy, S. Stakeholder perspectives on adaptive clinical trials: a scoping review. Trials. 2020;21(1):539.CrossRefGoogle ScholarPubMed
He, W, Kuznetsova, OM, Harmer, M, et al. Practical considerations and strategies for executing adaptive clinical trials. DIJ. 2012;46(2):160–74.Google Scholar
Dimairo, M, Pallmann, P, Wason, J, et al. The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. Trials. 2020;21(1):528.Google Scholar
Dimairo, M, Pallmann, P, Wason, J, et al. The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. BMJ. 2020;369:m115.Google Scholar
Detry, MA, Lewis, RJ, Broglio, KR, et al. Standards for the design, conduct, and evaluation of adaptive randomized clinical trials. Patient-Centered Outcomes Research Institute (PCORI); 2012.Google Scholar
Mayer, C, Perevozskaya, I, Leonov, S, et al. Simulation practices for adaptive trial designs in drug and device development.Stat Biopharm Res. 2019;11(4):325–35.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.CrossRefGoogle ScholarPubMed
Bhatt, DL, Mehta, C. Adaptive designs for clinical trials. N Engl J Med. 2016;375(1):6574.CrossRefGoogle ScholarPubMed
Berry, DA. Bayesian clinical trials. Nat Rev Drug Discov. 2006;5(1):2736.Google Scholar
Senn, S. You may believe you are a Bayesian but you are probably wrong. Error Statistics Philosophy; 2011.Google Scholar
Tversky, A, Kahneman, D. Judgment under uncertainty: heuristics and biases. Science. 1974;185(4157):1124–31.Google Scholar
Dave, C, Wolfe, KW. On confirmation bias and deviations from Bayesian updating. Working Paper, University of Pittsburgh; 2004.Google Scholar
Johnson, AA, Ott, MQ, Dogucu, M. Bayes Rules!: An Introduction to Applied Bayesian Modeling. CRC Press; 2022.CrossRefGoogle Scholar
Woolston, C. Psychology journal bans P values. Nature. 2015;519(7541):9.Google Scholar
Singh Chawla, D. ‘One-size-fits-all’ threshold for P values under fire. Nature News. 2017.Google Scholar
Yarnell, CJ, Abrams, D, Baldwin, MR, et al. Clinical trials in critical care: can a Bayesian approach enhance clinical and scientific decision making? Lancet Resp Med. 2021;9(2):207–16.Google Scholar
Greenland, S, Senn, SJ, Rothman, KJ, et al. Statistical tests, P values, confidence intervals, and power: a guide to misinterpretations. Eur J Epidemiol. 2016;31(4):337–50.CrossRefGoogle Scholar
Wagenmakers, EJ. A practical solution to the pervasive problems of p values. Psychon Bull Rev. 2007;14(5):779804.CrossRefGoogle Scholar
Berry, DA. Interim analysis in clinical trials: the role of the likelihood principle. Am Stat. 1987;41(2):117–22.Google Scholar
United States Department of Health and Human Services, Food and Drug Administration. Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics Guidance for Industry.United States Department of Health and Human Services; 2022. www.fda.gov/media/120721/download.Google Scholar
United States Department of Health and Human Services, Food and Drug Administration. Adaptive Designs for Clinical Trials of Drugs and Biologics. Guidance for Industry. Center for Biologics Evaluation and Research (CBER). 2019.Google Scholar
United States Department of Health and Human Services, Food and Drug Administration. Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics Guidance for Industry (Draft Guidance). United States Department of Health and Human Services; 2018 www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM621817.pdfGoogle Scholar
Proschan, M, Evans, S. Resist the temptation of response-adaptive randomization. Clin Infect Dis. 2020;71(11):3002–4.Google Scholar
Angus, DC. Optimizing the trade-off between learning and doing in a pandemic. JAMA. 2020;323(19):1895–6.Google Scholar
Meurer, WJ, Lewis, RJ, Berry, DA. Adaptive clinical trials: a partial remedy for the therapeutic misconception? JAMA. 2012;307(22):2377–8.Google Scholar
Thall, P, Fox, P, Wathen, J. Statistical controversies in clinical research: scientific and ethical problems with adaptive randomization in comparative clinical trials. Ann Oncol. 2015;26(8):1621–8.Google Scholar
Viele, K, Broglio, K, McGlothlin, A, Saville, BR. Comparison of methods for control allocation in multiple arm studies using response adaptive randomization. Clin Trials. 2020;17(1):5260.Google Scholar
Zhao, W, Durkalski, V. Managing competing demands in the implementation of response‐adaptive randomization in a large multicenter phase III acute stroke trial. Stat Med. 2014;33(23):4043–52.Google Scholar
Wason, JM, Brocklehurst, P, Yap, C. When to keep it simple – adaptive designs are not always useful. BMC Med. 2019;17(1):17.Google Scholar
Senn, S. Being efficient about efficacy estimation. Stat Biopharm Res. 2013;5(3):204–10.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;125:18.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):116.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
Yusuf, S, Collins, R, Peto, R. Why do we need some large, simple randomized trials? Stat Med. 1984;3(4):409–20.Google Scholar
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.Google Scholar
Woodcock, J, LaVange, LM. Master protocols to study multiple therapies, multiple diseases, or both. N Engl J Med. 2017;377(1):6270.Google Scholar
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
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
Simon, R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989;10(1):110.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):6774.Google Scholar
Bauer, P, Bretz, F, Dragalin, V, Konig, F, Wassmer, G. Twenty-five years of confirmatory adaptive designs: opportunities and pitfalls. Stat Med. 2016;35(3):325–47.Google Scholar
Bogin, V. Master protocols: new directions in drug discovery. Contemp Clin Trials Commun. 2020;18:100568.Google Scholar
Grieve, AP. Response-adaptive clinical trials: case studies in the medical literature. Pharm Stat. 2017;16(1):6486.CrossRefGoogle ScholarPubMed
Angus, DC, Alexander, BM, Berry, S, et al. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov. 2019;18(10):797808.Google Scholar
Wathen, JK, Thall, PF. A simulation study of outcome adaptive randomization in multi-arm clinical trials. Clin Trials. 2017;14(5):432–40.Google Scholar

References

Wason, JM, Brocklehurst, P, Yap, C. When to keep it simple – adaptive designs are not always useful. BMC Med. 2019;17(1):17.CrossRefGoogle Scholar
Antoniou, M, Kolamunnage-Dona, R, Wason, J, et al. Biomarker-guided trials: challenges in practice. Contemp Clin Trials Commun. 2019;16:100493.Google Scholar
Lee, KM, Wason, J, Stallard, N. To add or not to add a new treatment arm to a multiarm study: a decision‐theoretic framework. Stat Med. 2019;38(18):3305–21.Google Scholar
Yusuf, S, Collins, R, Peto, R. Why do we need some large, simple randomized trials? Stat Med. 1984;3(4):409–20.Google Scholar
Krendyukov, A, Singhvi, S, Zabransky, M. Value of adaptive trials and surrogate endpoints for clinical decision-making in rare cancers. Front Oncol. 2021;11:636561.Google Scholar
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
Woodcock, J, LaVange, LM. Master protocols to study multiple therapies, multiple diseases, or both. N Eng J Medicine. 2017;377(1):6270.Google Scholar
DAMOCLES Study Group. A proposed charter for clinical trial data monitoring committees: helping them to do their job well. Lancet. 2005;365(9460):711–22.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):97100.Google Scholar
Sydes, MR, Parmar, MK, 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
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
Chan, AW, Tetzlaff, JM, Altman, DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200207.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):797807.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
Mayer, C, Perevozskaya, I, Leonov, S, et al. Simulation practices for adaptive trial designs in drug and device development. Stat Biopharm Res. 2019;11(4):325–35.Google Scholar
United States Department of Health and Human Services, Food and Drug Administration. Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics Guidance for Industry. United States Department of Health and Human Services; 2022. www.fda.gov/media/120721/downloadGoogle Scholar
United States Department of Health and Human Services, Food and Drug Administration. Adaptive Designs for Clinical Trials of Drugs and Biologics. Guidance for Industry. Center for Biologics Evaluation and Research (CBER); 2019.Google Scholar
U.S. Food and Drug Administration. Adaptive Designs for Medical Device Clinical Studies Guidance for Industry and Food and Drug Administration Staff. United States Department of Health and Human Services; 2016.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
Marchenko, O, Nolan, C. Implementing adaptive designs: operational considerations, putting it all together. In He, W, Pinheiro, J, Kuznetsova, OM, editors. Practical Considerations for Adaptive Trial Design and Implementation, pp. 203–23. Springer; 2014.Google Scholar
Senn, S. Being efficient about efficacy estimation. Stat Biopharm Res. 2013;5(3):204–10.CrossRefGoogle Scholar
Baldi, I, Azzolina, D, Soriani, N, et al. Overrunning in clinical trials: some thoughts from a methodological review. Trials. 2020;21(1):668.Google Scholar
Whitehead, J. Overrunning and underrunning in sequential clinical trials. Control Clin Trials. 1992;13(2):106–21.Google Scholar
Broglio, K. Randomization in clinical trials: permuted blocks and stratification. JAMA. 2018;319(21):2223–4.CrossRefGoogle ScholarPubMed
Kuznetsova, OM. Randomization challenges in adaptive design studies. In He, W, Pinheiro, J, Kuznetsova, OM, editors. Practical Considerations for Adaptive Trial Design and Implementation, pp. 157–81. Springer; 2014.Google Scholar
Bargaje, C. Good documentation practice in clinical research. Perspect Clin Res. 2011;2(2):5963.Google Scholar
Detry, MA, Lewis, RJ, Broglio, KR, et al. Standards for the Design, Conduct, and Evaluation of Adaptive Randomized Clinical Trials. Patient-Centered Outcomes Research Institute (PCORI); 2012.Google Scholar
Collignon, O, Schiel, A, Burman, CF, et al. Estimands and complex innovative designs. Clin Pharmacol Ther. 2022. Online ahead of print.CrossRefGoogle Scholar
Posch, M, Bauer, P. Adaptive budgets in clinical trials. Stat Biopharm Res. 2013;5(4):282–92.Google Scholar
Ravandi, F, Ritchie, EK, Sayar, H, et al. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015;16(9):1025–36.CrossRefGoogle ScholarPubMed
Angus, DC, Alexander, BM, Berry, S, et al. Adaptive platform trials: definition, design, conduct and reporting considerations. Nat Rev Drug Discov. 2019;18(10):797808.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×