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-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-28T16:44:02.124Z Has data issue: false hasContentIssue false

Chapter 9 - Case Studies of Adaptive Trial Designs

from Part IV - Case Studies of 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 six case studies of adaptive clinical trials. This chapter is intended to complement the previous chapters. We have organised the case studies by their main adaptive design feature. Each case study describes the background of individual trial and summarises key design details and overall results. Our presentation and discussion do not necessarily represent the official view of the trial investigators. Our discussion is intended to improve the reader’s general literacy and comprehension of published results of adaptive clinical trials.

Keywords

adaptive trial designsgroup sequential designsseamless designsample size re-assessmentresponse adaptive randomisationenrichment design
Type
Chapter
Information
Introduction to Adaptive Trial Designs and Master Protocols , pp. 101 - 114
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

Zajicek, JP, Hobart, JC, Slade, A, et al. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. 2012;83(11):1125–32.CrossRefGoogle ScholarPubMed
Bethoux, F, Marrie, RA. A cross-sectional study of the impact of spasticity on daily activities in multiple sclerosis. Patient. 2016;9(6):537–46.CrossRefGoogle ScholarPubMed
O’Brien, PC, Fleming, TR. A multiple testing procedure for clinical trials. Biometrics. 1979;35(3):549–56.Google ScholarPubMed
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
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.CrossRefGoogle ScholarPubMed
Sevransky, JE, Rothman, RE, Hager, DN, et al. Effect of vitamin C, thiamine, and hydrocortisone on ventilator- and vasopressor-free days in patients with sepsis: the VICTAS randomized clinical trial. JAMA. 2021;325(8):742–50.CrossRefGoogle ScholarPubMed
Lindsell, CJ, McGlothlin, A, Nwosu, S, et al. Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. Trials. 2019;20(1):670.CrossRefGoogle Scholar
Hager, DN, Hooper, MH, Bernard, GR, et al. The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) Protocol: a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial. Trials. 2019;20(1):197.Google Scholar
Bauchner, H, Fontanarosa, PB, Golub, RM. Funding and DSMB membership in the VICTAS clinical trial. JAMA. 2021;325(8):751–2.Google Scholar
Galloway, DA, Laimins, LA. Human papillomaviruses: shared and distinct pathways for pathogenesis. Curr Opin Virol. 2015;14:87–92.CrossRefGoogle ScholarPubMed
Plummer, M, de Martel, C, Vignat, J, et al. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health. 2016;4(9):e609–16.CrossRefGoogle ScholarPubMed
Joura, EA, Leodolter, S, Hernandez-Avila, M, et al. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007;369(9574):1693–702.CrossRefGoogle ScholarPubMed
Joura, EA, Giuliano, AR, Iversen, OE, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711–23.CrossRefGoogle ScholarPubMed
Huh, WK, Joura, EA, Giuliano, AR, et al. Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: a randomised, double-blind trial. Lancet. 2017;390(10108):2143–59.Google Scholar
Chen, YH, Gesser, R, Luxembourg, A. A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges. Clin Trials. 2015;12(1):84–90.CrossRefGoogle ScholarPubMed
Reverberi, R. The statistical analysis of immunohaematological data. Blood Transfus. 2008;6(1):37–45.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.Google Scholar
Breems, DA, Van Putten, WL, Huijgens, PC, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol. 2005;23(9):1969–78.Google Scholar
Lancet, JE, Roboz, GJ, Cripe, LD, et al. A phase 1b/2 study of vosaroxin in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia. Haematologica. 2015;100(2):231–7.Google Scholar
Mehta, CR, Pocock, SJ. Adaptive increase in sample size when interim results are promising: a practical guide with examples. Stat Med. 2011;30(28):3267–84.Google Scholar
David, FS, Bobulsky, S, Schulz, K, Patel, N. Creating value with financially adaptive clinical trials. Nat Rev Drug Discov. 2015;14(8):523–4.Google Scholar
Jones, AE, Puskarich, MA, Shapiro, NI, et al. Effect of levocarnitine vs placebo as an adjunctive treatment for septic shock: the Rapid Administration of Carnitine in Sepsis (RACE) randomized clinical trial. JAMA Netw Open. 2018;1(8):e186076.CrossRefGoogle ScholarPubMed
Calvani, M, Reda, E, Arrigoni-Martelli, E. Regulation by carnitine of myocardial fatty acid and carbohydrate metabolism under normal and pathological conditions. Basic Res Cardiol. 2000;95(2):75–83.Google Scholar
Krams, M, Lees, KR, Hacke, W, et al. Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN): an adaptive dose-response study of UK-279,276 in acute ischemic stroke. Stroke. 2003;34(11):2543–8.CrossRefGoogle ScholarPubMed
Grieve, AP, Krams, M. ASTIN: a Bayesian adaptive dose-response trial in acute stroke. Clin Trials. 2005;2(4):340–51.CrossRefGoogle ScholarPubMed
Jones, RL, Ravi, V, Brohl, AS, et al. Efficacy and safety of TRC105 plus pazopanib vs pazopanib alone for treatment of patients with advanced angiosarcoma: a randomized clinical trial. JAMA Oncol. 2022;8(5):740–7.Google Scholar
Mehta, CR, Liu, L, Theuer, C. An adaptive population enrichment phase III trial of TRC105 and pazopanib versus pazopanib alone in patients with advanced angiosarcoma (TAPPAS trial). Ann Oncol. 2019; 30(1):103–8.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] 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
×