982,912 research outputs found

    Learning when to skim and when to read

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    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

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    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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