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Jonathan Siegel

Publications and source records attributed to Jonathan Siegel.

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Entropy-based convergence rates of greedy algorithms

We present convergence estimates of two types of greedy algorithms in terms of the metric entropy of underlying compact sets. In the first part, we measure the error of a standard greedy reduced basis method for parametric PDEs by the metric entropy of the solution manifold in Banach spaces. This contrasts with the classical analysis based on the Kolmogorov n-widths and enables us to obtain direct comparisons between the greedy algorithm error and the entropy numbers, where the multiplicative constants are explicit and simple. The entropy-based convergence estimate is sharp and improves upon the classical width-based analysis of reduced basis methods for elliptic model problems. In the second part, we derive a novel and simple convergence analysis of the classical orthogonal greedy algorithm for nonlinear dictionary approximation using the metric entropy of the symmetric convex hull of the dictionary. This also improves upon existing results by giving a direct comparison between the algorithm error and the metric entropy.

math.NA

Time-to-event estimands and loss to follow-up in oncology in light of the estimands framework

Time-to-event estimands are central to many oncology clinical trials. The estimand framework (addendum to the ICH E9 guideline) calls for precisely defining the treatment effect of interest to align with the clinical question of interest and requires predefining the handling of intercurrent events that occur after treatment initiation and either preclude the observation of an event of interest or impact the interpretation of the treatment effect. We discuss a practical problem in clinical trial design and execution, i.e. in some clinical contexts it is not feasible to systematically follow patients to an event of interest. Loss to follow-up in the presence of intercurrent events can affect the meaning and interpretation of the study results. We provide recommendations for trial design, stressing the need for close alignment of the clinical question of interest and study design, impact on data collection and other practical implications. When patients cannot be systematically followed, compromise may be necessary to select the best available estimand that can be feasibly estimated under the circumstances. We discuss the use of sensitivity and supplementary analyses to examine assumptions of interest.

stat.AP

Assessing the Impact of COVID-19 on the Objective and Analysis of Oncology Clinical Trials -- Application of the Estimand Framework

COVID-19 outbreak has rapidly evolved into a global pandemic. The impact of COVID-19 on patient journeys in oncology represents a new risk to interpretation of trial results and its broad applicability for future clinical practice. We identify key intercurrent events that may occur due to COVID-19 in oncology clinical trials with a focus on time-to-event endpoints and discuss considerations pertaining to the other estimand attributes introduced in the ICH E9 addendum. We propose strategies to handle COVID-19 related intercurrent events, depending on their relationship with malignancy and treatment and the interpretability of data after them. We argue that the clinical trial objective from a world without COVID-19 pandemic remains valid. The estimand framework provides a common language to discuss the impact of COVID-19 in a structured and transparent manner. This demonstrates that the applicability of the framework may even go beyond what it was initially intended for.

q-bio.OT