17,650 research outputs found

    Evaluating hybrid controls methodology in early-phase oncology trials: a simulation study based on the MORPHEUS-UC trial

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    Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls from one or more sources of historical trial data [HTD]) can be used to increase the statistical precision. Here we assess combining two sources of Roche HTD to construct a hybrid control in targeted therapy for decision-making via an extensive simulation study. Our simulations are based on the real data of one of the experimental arms and the control arm of the MORPHEUS-UC Phase Ib/II study and two Roche HTD for atezolizumab monotherapy. We consider potential complications such as model misspecification, unmeasured confounding, different sample sizes of current treatment groups, and heterogeneity among the three trials. We evaluate two frequentist methods (with both Cox and Weibull accelerated failure time [AFT] models) and three different priors in Bayesian dynamic borrowing (with a Weibull AFT model), and modifications within each of those, when estimating the effect of treatment on survival outcomes and measures of effect such as marginal hazard ratios. We assess the performance of these methods in different settings and potential of generalizations to supplement decisions in early-phase oncology trials. The results show that the proposed joint frequentist methods and noninformative priors within Bayesian dynamic borrowing with no adjustment on covariates are preferred, especially when treatment effects across the three trials are heterogeneous. For generalization of hybrid control methods in such settings we recommend more simulation studies.Comment: 34 pages, 3 figures, 5 tables. To be appear in Pharmaceutical Statistic

    Raising the visibility of protected data: A pilot data catalog project

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    Sharing research data that is protected for legal, regulatory, or contractual reasons can be challenging and current mechanisms for doing so may act as barriers to researchers and discourage data sharing. Additionally, the infrastructure commonly used for open data repositories does not easily support responsible sharing of protected data. This chapter presents a case study of an academic university library’s work to configure the existing institutional data repository to function as a data catalog. By engaging in this project, university librarians strive to enhance visibility and access to protected datasets produced at the institution and cultivate a data sharing culture

    Motivation, Design, and Ubiquity: A Discussion of Research Ethics and Computer Science

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    Modern society is permeated with computers, and the software that controls them can have latent, long-term, and immediate effects that reach far beyond the actual users of these systems. This places researchers in Computer Science and Software Engineering in a critical position of influence and responsibility, more than any other field because computer systems are vital research tools for other disciplines. This essay presents several key ethical concerns and responsibilities relating to research in computing. The goal is to promote awareness and discussion of ethical issues among computer science researchers. A hypothetical case study is provided, along with questions for reflection and discussion.Comment: Written as central essay for the Computer Science module of the LANGURE model curriculum in Research Ethic

    Informed Bayesian survival analysis

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    Informed Bayesian survival analysis

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