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At least 55 records · Page 3

Exploration of a Potential Desirability of Outcome Ranking Endpoint for Complicated Intra-Abdominal Infections Using 9 Registrational Trials for Antibacterial Drugs

Abstract Background Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI). Methods Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and, for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator. Results Three key findings informed the cIAI-specific DOOR endpoint: (1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; (2) infectious complications of cIAI were diverse; and (3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment versus comparator. Conclusions We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease–specific DOOR endpoints.

Immunology↗

Exploration of a Potential DOOR Endpoint for Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia Using Six Registrational Trials for Antibacterial Drugs

Abstract Background Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). Methods Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator. Results DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Although infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar. Conclusions Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design.

Immunology↗

Quantifying parameters for Bayesian prior assumptions when estimating the probability of failure of software

Software reliability has become increasingly important, especially in life-critical situations. The ability to measure the results of testing and to quantify software reliability is needed. If this is accomplished, a certain minimum amount of reliability for a piece of software can be specified, and testing and/or other analysis may be done until that minimum number has been attained. There are many models for estimating software reliability. The accuracy of these models has been challenged and many revisions for the models and recalibration techniques have been devised. Of particular interest is the method of estimating the probability of failure of software when no failures have yet occurred in its current version as described by Miller. This model uses black box testing with formulae based on Bayesian estimation. The focus is on three interrelated issues: estimating the probability of failure when testing has revealed no errors; modifying this estimation when the input use distribution does not match the test distribution; and combining the results from random testing with other relevant information to obtain a possibly more accurate estimate of the probability of failure. Obtaining relevant information about the software and combining the results for a better estimate for the Miller model are discussed.

Long, Jacquelyn E.↗

Fisher classifier and its probability of error estimation

Computationally efficient expressions are derived for estimating the probability of error using the leave-one-out method. The optimal threshold for the classification of patterns projected onto Fisher's direction is derived. A simple generalization of the Fisher classifier to multiple classes is presented. Computational expressions are developed for estimating the probability of error of the multiclass Fisher classifier.

Chittineni, C. B.↗

A Method to Estimate the Probability That Any Individual Cloud-to-Ground Lightning Stroke Was Within Any Radius of Any Point

A new technique has been developed to estimate the probability that a nearby cloud-to-ground lightning stroke was within a specified radius of any point of interest. This process uses the bivariate Gaussian distribution of probability density provided by the current lightning location error ellipse for the most likely location of a lightning stroke and integrates it to determine the probability that the stroke is inside any specified radius of any location, even if that location is not centered on or even within the location error ellipse. This technique is adapted from a method of calculating the probability of debris collision with spacecraft. Such a technique is important in spaceport processing activities because it allows engineers to quantify the risk of induced current damage to critical electronics due to nearby lightning strokes. This technique was tested extensively and is now in use by space launch organizations at Kennedy Space Center and Cape Canaveral Air Force station.

Huddleston, Lisa L.↗

A Method to Estimate the Probability that Any Individual Cloud-to-Ground Lightning Stroke was Within Any Radius of Any Point

A new technique has been developed to estimate the probability that a nearby cloud-to-ground lightning stroke was within a specified radius of any point of interest. This process uses the bivariate Gaussian distribution of probability density provided by the current lightning location error ellipse for the most likely location of a lightning stroke and integrates it to determine the probability that the stroke is inside any specified radius of any location, even if that location is not centered on or even within the location error ellipse. This technique is adapted from a method of calculating the probability of debris collision with spacecraft. Such a technique is important in spaceport processing activities because it allows engineers to quantify the risk of induced current damage to critical electronics due to nearby lightning strokes. This technique was tested extensively and is now in use by space launch organizations at Kennedy Space Center and Cape Canaveral Air Force station. Future applications could include forensic meteorology.

Huddleston, Lisa↗

A Method to Estimate the Probability that any Individual Cloud-to-Ground Lightning Stroke was Within any Radius of any Point

A new technique has been developed to estimate the probability that a nearby cloud to ground lightning stroke was within a specified radius of any point of interest. This process uses the bivariate Gaussian distribution of probability density provided by the current lightning location error ellipse for the most likely location of a lightning stroke and integrates it to determine the probability that the stroke is inside any specified radius of any location, even if that location is not centered on or even with the location error ellipse. This technique is adapted from a method of calculating the probability of debris collision with spacecraft. Such a technique is important in spaceport processing activities because it allows engineers to quantify the risk of induced current damage to critical electronics due to nearby lightning strokes. This technique was tested extensively and is now in use by space launch organizations at Kennedy Space Center and Cape Canaveral Air Force Station. Future applications could include forensic meteorology.

Huddleston, Lisa L.↗

Investigation of estimators of probability density functions

Four research projects are summarized which include: (1) the generation of random numbers on the IBM 360/44, (2) statistical tests used to check out random number generators, (3) Specht density estimators, and (4) use of estimators of probability density functions in analyzing large amounts of data.

Speed, F. M.↗

Optimizing Probability of Detection Point Estimate Demonstration

Probability of detection (POD) analysis is used in assessing reliably detectable flaw size in nondestructive evaluation (NDE). MIL-HDBK-18231and associated mh18232POD software gives most common methods of POD analysis. Real flaws such as cracks and crack-like flaws are desired to be detected using these NDE methods. A reliably detectable crack size is required for safe life analysis of fracture critical parts. The paper provides discussion on optimizing probability of detection (POD) demonstration experiments using Point Estimate Method. POD Point estimate method is used by NASA for qualifying special NDE procedures. The point estimate method uses binomial distribution for probability density. Normally, a set of 29 flaws of same size within some tolerance are used in the demonstration. The optimization is performed to provide acceptable value for probability of passing demonstration (PPD) and achieving acceptable value for probability of false (POF) calls while keeping the flaw sizes in the set as small as possible.

Koshti, Ajay M.↗

Conservative Estimation of Tail Probabilities from Limited Sample Data

Several sparse-sample uncertainty quantification (UQ) methods are compared for conservative but not overly conservative estimation of small tail probabilities involving responses that lay beyond specified thresholds in the tails of probability distributions. Sixteen very differently shaped distributions (or probability density functions, PDFs) and tail probability magnitudes ranging from 10 -5 to 10 -1 are considered in order for the study to be relevant to a wide range of risk analysis and quantification of margins and uncertainty (QMU) problems. The emphasis of the study is on limited data regimes ranging from N = 2 to 20 samples, reflective of most experimental and some expensive computational situations. Relatively simple sparse-sample UQ methods tested for this regime involve statistical tolerance interval "Equivalent Normal and related "Ensemble of Normals" and "Superdistribution (SD) approaches. (The independently derived SD is effectively equivalent to the Bayesian posterior predictive distribution given the assumptions of the derivation.) The performance of the methods was generally improved for N ≥ 5 samples with a generalized Jackknife resampling technique, which determines a tail probability estimate by averaging estimates from smaller sub-samples. Several quantitative metrics for method conservatism and accuracy of tail probability estimation are used to assess and rank the methods' performance over many random trials for each test PDF and probability magnitude. A variant of Bootstrap resampling was also tried, but did not significantly improve tail probability estimates in most cases. Detailed results are presented from over 100-million tests over the above factors that provide useful granular information on which methods or combination of methods perform best in various areas of the factor space.

97 MATHEMATICS AND COMPUTING↗

An Empirical Model for Estimating the Probability of Electrical Short Circuits from Tin Whiskers-Part I

Existing risk simulations make the assumption that when a free tin whisker has bridged two adjacent exposed electrical conductors, the result is an electrical short circuit. This conservative assumption is made because shorting is a random event that has a currently unknown probability associated with it. Due to contact resistance, electrical shorts may not occur at lower voltage levels. In this experiment, we study the effect of varying voltage on the breakdown of the contact resistance which leads to a short circuit. From this data, we can estimate the probability of an electrical short, as a function of voltage, given that a free tin whisker has bridged two adjacent exposed electrical conductors. In addition, three tin whiskers grown from the same Space Shuttle Orbiter card guide used in the aforementioned experiment were cross sectioned and studied using a focused ion beam (FIB).

Courey, Karim↗

Estimating the Probability of Electrical Short Circuits from Tin Whiskers

To comply with lead-free legislation, many manufacturers have converted from tin-lead to pure tin finishes of electronic components. However, pure tin finishes have a greater propensity to grow tin whiskers than tin-lead finishes. Since tin whiskers present an electrical short circuit hazard in electronic components, simulations have been developed to quantify the risk of said short circuits occurring. Existing risk simulations make the assumption that when a free tin whisker has bridged two adjacent exposed electrical conductors, the result is an electrical short circuit. This conservative assumption is made because shorting is a random event that had an unknown probability associated with it. Note however that due to contact resistance electrical shorts may not occur at lower voltage levels. In our first article we developed an empirical probability model for tin whisker shorting. In this paper, we develop a more comprehensive empirical model using a refined experiment with a larger sample size, in which we studied the effect of varying voltage on the breakdown of the contact resistance which leads to a short circuit. From the resulting data we estimated the probability distribution of an electrical short, as a function of voltage. In addition, the unexpected polycrystalline structure seen in the focused ion beam (FIB) cross section in the first experiment was confirmed in this experiment using transmission electron microscopy (TEM). The FIB was also used to cross section two card guides to facilitate the measurement of the grain size of each card guide's tin plating to determine its finish .

Courey, Karim J.↗

Estimating the Probability of Electrical Short Circuits from Tin Whiskers

To comply with lead-free legislation, many manufacturers have converted from tin-lead to pure tin finishes of electronic components. However, pure tin finishes have a greater propensity to grow tin whiskers than tin-lead finishes. Since tin whiskers present an electrical short circuit hazard in electronic components, simulations have been developed to quantify the risk of said short circuits occurring. Existing risk simulations make the assumption that when a free tin whisker has bridged two adjacent exposed electrical conductors, the result is an electrical short circuit. This conservative assumption is made because shorting is a random event that had an unknown probability associated with it. Note however that due to contact resistance electrical shorts may not occur at lower voltage levels. In our first article we developed an empirical probability model for tin whisker shorting. In this paper, we develop a more comprehensive empirical model using a refined experiment with a larger sample size, in which we studied the effect of varying voltage on the breakdown of the contact resistance which leads to a short circuit. From the resulting data we estimated the probability distribution of an electrical short, as a function of voltage.

Courey, Karim J.↗

Developing an Empirical Model for Estimating the Probability of Electrical Short Circuits from Tin Whiskers

To comply with lead-free legislation, many manufacturers have converted from tin-lead to pure tin finishes of electronic components. However, pure tin finishes have a greater propensity to grow tin whiskers than tin-lead finishes. Since tin whiskers present an electrical short circuit hazard in electronic components, simulations have been developed to quantify the risk of said short circuits occurring. Existing risk simulations make the assumption that when a free tin whisker has bridged two adjacent exposed electrical conductors, the result is an electrical short circuit. This conservative assumption is made because shorting is a random event that had an unknown probability associated with it. Note however that due to contact resistance electrical shorts may not occur at lower voltage levels. In our first article we developed an empirical probability model for tin whisker shorting. In this paper, we develop a more comprehensive empirical model using a refined experiment with a larger sample size, in which we studied the effect of varying voltage on the breakdown of the contact resistance which leads to a short circuit. From the resulting data we estimated the probability distribution of an electrical short, as a function of voltage. In addition, the unexpected polycrystalline structure seen in the focused ion beam (FIB) cross section in the first experiment was confirmed in this experiment using transmission electron microscopy (TEM). The FIB was also used to cross section two card guides to facilitate the measurement of the grain size of each card guide's tin plating to determine its finish.

Courey, Karim J.↗

A Provably Accurate Randomized Sampling Algorithm for Logistic Regression

In statistics and machine learning, logistic regression is a widely-used supervised learning technique primarily employed for binary classification tasks. When the number of observations greatly exceeds the number of predictor variables, we present a simple, randomized sampling-based algorithm for logistic regression problem that guarantees high-quality approximations to both the estimated probabilities and the overall discrepancy of the model. Our analysis builds upon two simple structural conditions that boil down to randomized matrix multiplication, a fundamental and well-understood primitive of randomized numerical linear algebra. We analyze the properties of estimated probabilities of logistic regression when leverage scores are used to sample observations, and prove that accurate approximations can be achieved with a sample whose size is much smaller than the total number of observations. To further validate our theoretical findings, we conduct comprehensive empirical evaluations. Overall, our work sheds light on the potential of using randomized sampling approaches to efficiently approximate the estimated probabilities in logistic regression, offering a practical and computationally efficient solution for large-scale datasets.

Chowdhury, Agniva↗

A method for modeling bias in a person's estimates of likelihoods of events

It is of practical importance in decision situations involving risk to train individuals to transform uncertainties into subjective probability estimates that are both accurate and unbiased. We have found that in decision situations involving risk, people often introduce subjective bias in their estimation of the likelihoods of events depending on whether the possible outcomes are perceived as being good or bad. Until now, however, the successful measurement of individual differences in the magnitude of such biases has not been attempted. In this paper we illustrate a modification of a procedure originally outlined by Davidson, Suppes, and Siegel (3) to allow for a quantitatively-based methodology for simultaneously estimating an individual's subjective utility and subjective probability functions. The procedure is now an interactive computer-based algorithm, DSS, that allows for the measurement of biases in probability estimation by obtaining independent measures of two subjective probability functions (S+ and S-) for winning (i.e., good outcomes) and for losing (i.e., bad outcomes) respectively for each individual, and for different experimental conditions within individuals. The algorithm and some recent empirical data are described.

Nygren, Thomas E.↗

PRIME: A bottom-up approach to probabilistic rule development

PRIME is a system to be used by an intelligent machine to allow it to operate in an abstract but uncertain (or stochastic) environment. It maintains a model of the effects of the machine's actions in the form of a rule base, which is induced from experience. This bottom-up approach to rule development allows the model to adapt to changes in the environment. Each rule consists of a condition under which the rule is active, an action, the effect of the action on the environment, and an estimate of the probability of this effect occurring. The effect probabilities are used to model the uncertainty in the environment, permitting multiple possible effects for a single action under a particular set of conditions. The objective of the intelligent machine is to satisfy user-specified goals with maximum probability of success. PRIME fulfills this requirement in two ways: it continuously updates the rule base with the most recent information, to ensure the validity of the model; and it generates plans which have the maximum probability of achieving the goals, based on the probability estimates in the rule base. PRIME is composed of three main processes: exploration, generalization, and planning. In exploration, the machine executes various randomly chosen actions, observes the effects on the environment, and updates the rule base accordingly. This process is used to develop the rule base in simulation, as well as to supplement the current knowledge during normal operation. Generalization is the procedure used to induce general rules from experience, which is encoded in the form of specific rules. These general rules extend the machine's knowledge to situations which have not been encountered yet, thereby increasing the capability of the machine to plan effectively. Planning is the process of constructing an optimal sequence of actions to satisfy a goal, using the rule base to predict the effects of these actions and to determine the probability of success of the plan. The rule representation and many other data structures were specifically chosen to maximize the efficiency of these processes. A simulated environment was designed to test the performance of PRIME. The results of experimentation were largely negative. The main problem was that the domain coverage of the rules was inadequate for the number of rules stored in the rule base, due to redundancies in general rules and numerous rules covering ineffective actions. It was determined that a more efficient generalization, and some form of goal-directed exploration, are necessary in order to solve most of the current deficiencies in PRIME.

Miller, Scott A.↗