982,912 research outputs found
Learning when to skim and when to read
Many recent advances in deep learning for natural language processing have
come at increasing computational cost, but the power of these state-of-the-art
models is not needed for every example in a dataset. We demonstrate two
approaches to reducing unnecessary computation in cases where a fast but weak
baseline classier and a stronger, slower model are both available. Applying an
AUC-based metric to the task of sentiment classification, we find significant
efficiency gains with both a probability-threshold method for reducing
computational cost and one that uses a secondary decision network.Comment: 8 pages (4 article, 1 references, 3 appendix), 11 figures, 3 tables,
published at ACL2017 workshop Repl4NL
Integrating Phase 2 into Phase 3 based on an Intermediate Endpoint While Accounting for a Cure Proportion -- with an Application to the Design of a Clinical Trial in Acute Myeloid Leukemia
For a trial with primary endpoint overall survival for a molecule with
curative potential, statistical methods that rely on the proportional hazards
assumption may underestimate the power and the time to final analysis. We show
how a cure proportion model can be used to get the necessary number of events
and appropriate timing via simulation. If Phase 1 results for the new drug are
exceptional and/or the medical need in the target population is high, a Phase 3
trial might be initiated after Phase 1. Building in a futility interim analysis
into such a pivotal trial may mitigate the uncertainty of moving directly to
Phase 3. However, if cure is possible, overall survival might not be mature
enough at the interim to support a futility decision. We propose to base this
decision on an intermediate endpoint that is sufficiently associated with
survival. Planning for such an interim can be interpreted as making a
randomized Phase 2 trial a part of the pivotal trial: if stopped at the
interim, the trial data would be analyzed and a decision on a subsequent Phase
3 trial would be made. If the trial continues at the interim then the Phase 3
trial is already underway. To select a futility boundary, a mechanistic
simulation model that connects the intermediate endpoint and survival is
proposed. We illustrate how this approach was used to design a pivotal
randomized trial in acute myeloid leukemia, discuss historical data that
informed the simulation model, and operational challenges when implementing it.Comment: 23 pages, 3 figures, 3 tables. All code is available on github:
https://github.com/numbersman77/integratePhase2.gi
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