Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-pftt2 Total loading time: 0 Render date: 2024-06-09T03:11:39.222Z Has data issue: false hasContentIssue false

Chapter 14 - Practical Considerations for Adaptive Trial Designs and Master Protocols

from 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 ,
Edward J. Mills  and
J. Kyle Wathen
By
Jay J. H. Park ,
Edward J. Mills  and
J. Kyle Wathen
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

In this chapter, we review practical considerations for adaptive trial designs and master protocols. Planning adaptive trial designs and master protocols require resources and time. It is best to plan ahead with key stakeholders with statistical, content, and operational expertise to make the trial possible. Customised education and training plans will likely be required for the vendors, investigators, and other personnel involved in the trial. Critical thinking is needed from the personnel involved to create flexible technology systems and procedures required to execute these clinical trials. During the conduct, it is important to document what happened, maintain a proper firewall, and manage external communications effectively. For long-term platform trials, study adjustments may be unavoidable, but it is important that these adjustments are made before the patients are enrolled into the new study arm.

Keywords

adaptive trial designsmaster protocolspractical considerations
Type
Chapter
Information
Introduction to Adaptive Trial Designs and Master Protocols , pp. 160 - 170
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

Wason, JM, Brocklehurst, P, Yap, C. When to keep it simple – adaptive designs are not always useful. BMC Med. 2019;17(1):1–7.Google Scholar
Antoniou, M, Kolamunnage-Dona, R, Wason, J, et al. Biomarker-guided trials: challenges in practice. Contemp Clin Trials Commun. 2019;16:100493.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.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.CrossRefGoogle ScholarPubMed
Woodcock, J, LaVange, LM. Master protocols to study multiple therapies, multiple diseases, or both. N Eng J Medicine. 2017;377(1):62–70.CrossRefGoogle ScholarPubMed
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):97–100.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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):200–207.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):797–807.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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
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.Google Scholar
Baldi, I, Azzolina, D, Soriani, N, et al. Overrunning in clinical trials: some thoughts from a methodological review. Trials. 2020;21(1):668.CrossRefGoogle ScholarPubMed
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.Google Scholar
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):59–63.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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):797–808.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
×