Sequential multiple assignment randomization trials with enrichment design.

TitleSequential multiple assignment randomization trials with enrichment design.
Publication TypeJournal Article
Year of Publication2017
AuthorsLiu, Ying, Yuanjia Wang, and Donglin Zeng
JournalBiometrics
Volume73
Issue2
Pagination378-390
Date Published2017 06
ISSN1541-0420
KeywordsHumans, Patient Dropouts, Random Allocation, Research Design, Sample Size
Abstract

Sequential multiple assignment randomization trial (SMART) is a powerful design to study Dynamic Treatment Regimes (DTRs) and allows causal comparisons of DTRs. To handle practical challenges of SMART, we propose a SMART with Enrichment (SMARTER) design, which performs stage-wise enrichment for SMART. SMARTER can improve design efficiency, shorten the recruitment period, and partially reduce trial duration to make SMART more practical with limited time and resource. Specifically, at each subsequent stage of a SMART, we enrich the study sample with new patients who have received previous stages' treatments in a naturalistic fashion without randomization, and only randomize them among the current stage treatment options. One extreme case of the SMARTER is to synthesize separate independent single-stage randomized trials with patients who have received previous stage treatments. We show data from SMARTER allows for unbiased estimation of DTRs as SMART does under certain assumptions. Furthermore, we show analytically that the efficiency gain of the new design over SMART can be significant especially when the dropout rate is high. Lastly, extensive simulation studies are performed to demonstrate performance of SMARTER design, and sample size estimation in a scenario informed by real data from a SMART study is presented.

DOI10.1111/biom.12576
Alternate JournalBiometrics
Original PublicationSequential multiple assignment randomization trials with enrichment design.
PubMed ID27598622
PubMed Central IDPMC5339073
Grant ListP01 CA142538 / CA / NCI NIH HHS / United States
R01 NS073671 / NS / NINDS NIH HHS / United States
U01 NS082062 / NS / NINDS NIH HHS / United States