arXiv subjects

Constantine Frangakis

Publications and source records attributed to Constantine Frangakis.

4 recordsLinked to original sources

arXiv2025

Deterministic Global Optimization of the Acquisition Function in Bayesian Optimization: To Do or Not To Do?

Bayesian Optimization (BO) with Gaussian Processes relies on optimizing an acquisition function to determine sampling. We investigate the advantages and disadvantages of using a deterministic global solver (MAiNGO) compared to conventional local and stochastic global solvers (L-BFGS-B and multi-start, respectively) for the optimization of the acquisition function. For CPU efficiency, we set a time limit for MAiNGO, taking the best point as optimal. We perform repeated numerical experiments, initially using the Muller-Brown potential as a benchmark function, utilizing the lower confidence bound acquisition function; we further validate our findings with three alternative benchmark functions. Statistical analysis reveals that when the acquisition function is more exploitative (as opposed to exploratory), BO with MAiNGO converges in fewer iterations than with the local solvers. However, when the dataset lacks diversity, or when the acquisition function is overly exploitative, BO with MAiNGO, compared to the local solvers, is more likely to converge to a local rather than a global ly near-optimal solution of the black-box function. L-BFGS-B and multi-start mitigate this risk in BO by introducing stochasticity in the selection of the next sampling point, which enhances the exploration of uncharted regions in the search space and reduces dependence on acquisition function hyperparameters. Ultimately, suboptimal optimization of poorly chosen acquisition functions may be preferable to their optimal solution. When the acquisition function is more exploratory, BO with MAiNGO, multi-start, and L-BFGS-B achieve comparable probabilities of convergence to a globally near-optimal solution (although BO with MAiNGO may require more iterations to converge under these conditions).

math.OC↗

arXiv2024

Adaptive High-Level Tight Control of Prostate Cancer: A Path from From Terminal Disease to Chronic Condition

Metastatic prostate cancer is one of the leading causes of cancer-related morbidity and mortality worldwide. It is characterized by a high mortality rate and a poor prognosis. In this work, we explore how a clinical oncologist can apply a Stackelberg game-theoretic framework to prolong metastatic prostate cancer survival, or even make it chronic in duration. We utilize a Bayesian optimization approach to identify the optimal adaptive chemotherapeutic treatment policy for a single drug (Abiraterone) to maximize the time before the patient begins to show symptoms. We show that, with precise adaptive optimization of drug delivery, it is possible to significantly prolong the cancer suppression period, potentially converting metastatic prostate cancer from a terminal disease to a chronic disease for most patients, as supported by clinical and analytical evidence. We suggest that clinicians might explore the possibility of implementing a high-level tight control (HLTC) treatment, in which the trigger signals (i.e. biomarker levels) for drug administration and cessation are both high and close together, typically yield the best outcomes, as demonstrated through both computation and theoretical analysis. This simple insight could serve as a valuable guide for improving current adaptive chemotherapy treatments in other hormone-sensitive cancers.

q-bio.QM↗

arXiv2022

On Resolving Problems with Conditionality and Its Implications for Characterizing Statistical Evidence

The conditionality principle $C$ plays a key role in attempts to characterize the concept of statistical evidence. The standard version of $C$ considers a model and a derived conditional model, formed by conditioning on an ancillary statistic for the model, together with the data, to be equivalent with respect to their statistical evidence content. This equivalence is considered to hold for any ancillary statistic for the model but creates two problems. First, there can be more than one maximal ancillary in a given context and this leads to $C$ not being an equivalence relation and, as such, calls into question whether $C$ is a proper characterization of statistical evidence. Second, a statistic $A$ can change from ancillary to informative (in its marginal distribution) when another ancillary $B$ changes, from having one known distribution $P_{B},$ to having another known distribution $Q_{B}.$ This means that the stability of ancillarity differs across ancillary statistics and raises the issue of when a statistic can be said to be truly ancillary. It is therefore natural, and practically important, to limit conditioning to the set of ancillaries whose distribution is irrelevant to the ancillary status of any other ancillary statistic. This results in a family of ancillaries for which there is a unique maximal member. This also gives a new principle for inference, the stable conditionality principle, that satisfies the criteria required for any principle whose aim is to characterize statistical evidence.

math.ST↗

arXiv2019

Deductive semiparametric estimation in Double-Sampling Designs with application to PEPFAR

Non-ignorable dropout is common in studies with long follow-up time, and it can bias study results unless handled carefully. A double-sampling design allocates additional resources to pursue a subsample of the dropouts and find out their outcomes, which can address potential biases due to non-ignorable dropout. It is desirable to construct semiparametric estimators for the double-sampling design because of their robustness properties. However, obtaining such semiparametric estimators remains a challenge due to the requirement of the analytic form of the efficient influence function (EIF), the derivation of which can be ad hoc and difficult for the double-sampling design. Recent work has shown how the derivation of EIF can be made deductive and computerizable using the functional derivative representation of the EIF in nonparametric models. This approach, however, requires deriving the mixture of a continuous distribution and a point mass, which can itself be challenging for complicated problems such as the double-sampling design. We propose semiparametric estimators for the survival probability in double-sampling designs by generalizing the deductive and computerizable estimation approach. In particular, we propose to build the semiparametric estimators based on a discretized support structure, which approximates the possibly continuous observed data distribution and circumvents the derivation of the mixture distribution. Our approach is deductive in the sense that it is expected to produce semiparametric locally efficient estimators within finite steps without knowledge of the EIF. We apply the proposed estimators to estimating the mortality rate in a double-sampling design component of the President's Emergency Plan for AIDS Relief (PEPFAR) program. We evaluate the impact of double-sampling selection criteria on the mortality rate estimates.

stat.ME↗