A small n sequential multiple assignment randomized trial design for use in rare disease research.
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ABSTRACT: Background
Clinical trials in rare diseases are difficult to conduct due to the limited number of patients available with each disorder. We developed a Phase 2 trial which is a small n sequential multiple assignment randomized trial (snSMART) design to test several treatments for a rare disease for which no standard therapy exists.Purpose
This paper illustrates the design, sample size estimation and operating characteristics of an snSMART.Methods
We investigate the performance of a class of weighted Z statistics via computer simulations.Results
We demonstrate the increase in power over traditional single stage designs, and indicate how the power changes as a function of the weight given to each stage.Conclusion
The snSMART design is promising in a rare disease setting where several alternative treatments are under consideration and small sample sizes are necessary.
SUBMITTER: Tamura RN
PROVIDER: S-EPMC4695231 | biostudies-literature | 2016 Jan
REPOSITORIES: biostudies-literature
Publications
A small n sequential multiple assignment randomized trial design for use in rare disease research.
Tamura Roy N RN Krischer Jeffrey P JP Pagnoux Christian C Micheletti Robert R Grayson Peter C PC Chen Yeh-Fong YF Merkel Peter A PA
Contemporary clinical trials 20151114
<h4>Background</h4>Clinical trials in rare diseases are difficult to conduct due to the limited number of patients available with each disorder. We developed a Phase 2 trial which is a small n sequential multiple assignment randomized trial (snSMART) design to test several treatments for a rare disease for which no standard therapy exists.<h4>Purpose</h4>This paper illustrates the design, sample size estimation and operating characteristics of an snSMART.<h4>Methods</h4>We investigate the perfor ...[more]
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Project description:Background: Adaptive interventions are often used in individualized health care to meet the unique needs of clients. Recently, more researchers have adopted the Sequential Multiple Assignment Randomized Trial (SMART), a type of research design, to build optimal adaptive interventions. SMART requires research participants to be randomized multiple times over time, depending upon their response to earlier interventions. Despite the increasing popularity of SMART designs, conducting a successful SMART study poses unique technological and logistical challenges (e.g., effectively concealing and masking allocation sequence to investigators, involved health care providers, and subjects) in addition to other challenges common to all study designs (e.g., study invitations, eligibility screening, consenting procedures, and data confidentiality protocols). Research Electronic Data Capture (REDCap) is a secure, browser-based web application widely used by researchers for data collection. REDCap offers unique features that support researchers’ ability to conduct rigorous SMARTs. This manuscript provides an effective strategy for performing automatic double randomization for SMARTs using REDCap. Methods: Between January and March 2022, we conducted a SMART using a sample of adult (age 18 and older) New Jersey residents to optimize an adaptive intervention to increase COVID-19 testing uptake. In the current report, we discuss how we used REDCap for our SMART, which required double randomization. Further, we share our REDCap project XML file for future investigators to use when designing and conducting SMARTs. Results: We report on the randomization feature that REDCap offers and describe how the study team automated an additional randomization that was required for our SMART. An application programming interface was used to automate the double randomizations in conjunction with the randomization feature provided by REDCap. Conclusions: REDCap offers powerful tools to facilitate the implementation of longitudinal data collection and SMARTs. Investigators can make use of this electronic data capturing system to reduce errors and bias in the implementation of their SMARTs by automating double randomization. Trial registration: The SMART study was prospectively registered at Clinicaltrials.gov; registration number: NCT04757298, date of registration: 17/02/2021. Keywords: Research Electronic Data Capture (REDCap), randomized controlled trials (RCT), adaptive interventions, Sequential Multiple Assignment Randomized Trial (SMART), randomization, experimental design, reducing human errors, automation.
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