interAdapt -- An Interactive Tool for Designing and Evaluating Randomized Trials with Adaptive Enrollment Criteria

The interAdapt R package is designed to be used by statisticians and clinical investigators to plan randomized trials. It can be used to determine if certain adaptive designs offer tangible benefits compared to standard designs, in the context of investigators' specific trial goals and constraints. Specifically, interAdapt compares the performance of trial designs with adaptive enrollment criteria versus standard (non-adaptive) group sequential trial designs. Performance is compared in terms of power, expected trial duration, and expected sample size. Users can either work directly in the R console, or with a user-friendly shiny application that requires no programming experience. Several added features are available when using the shiny application. For example, the application allows users to immediately download the results of the performance comparison as a csv-table, or as a printable, html-based report.Comment: 14 pages, 2 figures (software screenshots); v2 includes command line function descriptio

STOCHASTIC OPTIMIZATION OF ADAPTIVE ENRICHMENT DESIGNS FOR TWO SUBPOPULATIONS

An adaptive enrichment design is a randomized trial that allows enrollment criteria to be modified at interim analyses, based on a preset decision rule. When there is prior uncertainty regarding treatment effect heterogeneity, these trial designs can provide improved power for detecting treatment effects in subpopulations. We present a simulated annealing approach to search over the space of decision rules and other parameters for an adaptive enrichment design. The goal is to minimize the expected number enrolled or expected duration, while preserving the appropriate power and Type I error rate. We also explore the benefits of parallel computation in the context of this goal. We find that optimized designs can be substantially more efficient than simpler designs using Pocock or O\u27Brien-Fleming boundaries

SENSITIVITY OF TRIAL PERFORMANCE TO DELAY OUTCOMES, ACCRUAL RATES, AND PROGNOSTIC VARIABLES BASED ON A SIMULATED RANDOMIZED TRIAL WITH ADAPTIVE ENRICHMENT

Adaptive enrichment designs involve rules for restricting enrollment to a subset of the population during the course of an ongoing trial. This can be used to target those who benefit from the experimental treatment. To leverage prognostic information in baseline variables and short-term outcomes, we use a semiparametric, locally efficient estimator, and investigate its strengths and limitations compared to standard estimators. Through simulation studies, we assess how sensitive the trial performance (Type I error, power, expected sample size, trial duration) is to different design characteristics. Our simulation distributions mimic features of data from the Alzheimer’s Disease Neuroimaging Initiative, and involve two subpopulations of interest based on a generic marker. We investigate the impact of the following design characteristics: the accrual rate, the delay time between enrollment and observation of the primary outcome, and the prognostic value of baseline variables and short-term outcomes. We apply information-based monitoring, and evaluate how accurately information can be estimated in an ongoing trial

Presidential Administration: An Intellectual and Legal History, 1888-1938

This dissertation explores the intellectual and legal history of presidential administration — that is, the president’s ability to direct the operations of the administrative state. The dissertation argues that presidential administration was closely connected to changing ideas about how to realize democratic government. It shows how, in the late 19th and early 20th century, the presidency acquired the institutions that lay the foundations for executive control of administration. This was a deliberate reform project, driven by ideas about what would make government responsible. The dissertation tells this story by tracking transformations in democratic thought and law through attention to court cases and scholarship, among other genres, and looks at both published and archival sources. It draws on methods from legal history, intellectual history, and American Political Development, and occasionally makes use of an Atlantic perspective. Besides historians, law professors, and political scientists, it may be of interest to scholars of the presidency, public administration, and analysts of current legal debates about presidential power and administration

Approximating fluid schedules in packet-switched networks

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mathematics, 2004.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 145-151).We consider a problem motivated by the desire to provide exible, rate-based, quality of service guarantees for packets sent over switches and switch networks. Our focus is solving a type of on-line, traffic scheduling problem, whose input at each time step is a set of desired traffic rates through the switch network. These traffic rates in general cannot be exactly achieved since they treat the incoming data as fluid, that is, they assume arbitrarily small fractions of packets can be transmitted at each time step. The goal of the traffic scheduling problem is to closely approximate the given sequence of traffic rates by a sequence of switch uses throughout the network in which only whole packets are sent. We prove worst-case bounds on the additional delay and buffer use that result from using such an approximation. These bounds depend on the network topology, the resources available to the scheduler, and the types of fluid policy allowed.by Michael Aaron Rosenblum.Ph.D

Solstice: An Electronic Journal of Geography and Mathematics, Volume XIV, Number 2

This document was delivered over the internet. The .zip file contains all static images, animated images, and text files.The purpose of Solstice is to promote interaction between geography and mathematics. Articles in which elements of one discipline are used to shed light on the other are particularly sought. Also welcome, are original contributions that are purely geographical or purely mathematical. These may be prefaced (by editor or author) with commentary suggesting directions that might lead toward the desired interaction. Contributed articles will be refereed by geographers and/or mathematicians. Invited articles will be screened by suitable members of the editorial board. IMaGe is open to having authors suggest, and furnish material for, new regular features.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58247/2/win03.ziphttp://deepblue.lib.umich.edu/bitstream/2027.42/58247/3/2003SolsticeVol14.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/58247/5/SolsticeVolXIVNo2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/58247/6/SolsticeVolXIVNo2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/58247/8/SolsticeVolXIVNo2.pdfDescription of SolsticeVolXIVNo2.pdf : Cover of JournalDescription of 2003SolsticeVol14.pdf : Solstice, 2003, Numbers 1 and 2. Contains attachments.Description of SolsticeVolXIVNo2.pdf : Cover of JournalDescription of SolsticeVolXIVNo2.pdf : Cover fil

Solstice: An Electronic Journal of Geography and Mathematics, Volume XVI, Number 1

This document was delivered over the internet. The .zip file contains all static images, animated images, and text files.The purpose of Solstice is to promote interaction between geography and mathematics. Articles in which elements of one discipline are used to shed light on the other are particularly sought. Also welcome, are original contributions that are purely geographical or purely mathematical. These may be prefaced (by editor or author) with commentary suggesting directions that might lead toward the desired interaction. Contributed articles will be refereed by geographers and/or mathematicians. Invited articles will be screened by suitable members of the editorial board. IMaGe is open to having authors suggest, and furnish material for, new regular features.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58253/2/sum05.ziphttps://deepblue.lib.umich.edu/bitstream/2027.42/58253/3/SolsticeVolXVINo1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/58253/5/SolsticeVolXVINo1.pdfDescription of SolsticeVolXVINo1.pdf : Cover of JournalDescription of SolsticeVolXVINo1.pdf : Cover fil