The Experts below are selected from a list of 13464 Experts worldwide ranked by ideXlab platform
Lisa V Hampson - One of the best experts on this subject based on the ideXlab platform.
-
designing multi arm multi stage clinical trials using a risk Benefit Criterion for treatment selection
Statistics in Medicine, 2016Co-Authors: Thomas Jaki, Lisa V HampsonAbstract:Multi-arm clinical trials that compare several active treatments to a common control have been proposed as an efficient means of making an informed decision about which of several treatments should be evaluated further in a confirmatory study. Additional efficiency is gained by incorporating interim analyses and, in particular, seamless Phase II/III designs have been the focus of recent research. Common to much of this work is the constraint that selection and formal testing should be based on a single efficacy endpoint, despite the fact that in practice, safety considerations will often play a central role in determining selection decisions. Here, we develop a multi-arm multi-stage design for a trial with an efficacy and safety endpoint. The safety endpoint is explicitly considered in the formulation of the problem, selection of experimental arm and hypothesis testing. The design extends group-sequential ideas and considers the scenario where a minimal safety requirement is to be fulfilled and the treatment yielding the best combined safety and efficacy trade-off satisfying this constraint is selected for further testing. The treatment with the best trade-off is selected at the first interim analysis, while the whole trial is allowed to compose of J analyses. We show that the design controls the familywise error rate in the strong sense and illustrate the method through an example and simulation. We find that the design is robust to misspecification of the correlation between the endpoints and requires similar numbers of subjects to a trial based on efficacy alone for moderately correlated endpoints. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
-
designing multi arm multi stage clinical trials using a risk Benefit Criterion for treatment selection
Statistics in Medicine, 2016Co-Authors: Thomas Jaki, Lisa V HampsonAbstract:Multi-arm clinical trials that compare several active treatments to a common control have been proposed as an efficient means of making an informed decision about which of several treatments should be evaluated further in a confirmatory study. Additional efficiency is gained by incorporating interim analyses and, in particular, seamless Phase II/III designs have been the focus of recent research. Common to much of this work is the constraint that selection and formal testing should be based on a single efficacy endpoint, despite the fact that in practice, safety considerations will often play a central role in determining selection decisions. Here, we develop a multi-arm multi-stage design for a trial with an efficacy and safety endpoint. The safety endpoint is explicitly considered in the formulation of the problem, selection of experimental arm and hypothesis testing. The design extends group-sequential ideas and considers the scenario where a minimal safety requirement is to be fulfilled and the treatment yielding the best combined safety and efficacy trade-off satisfying this constraint is selected for further testing. The treatment with the best trade-off is selected at the first interim analysis, while the whole trial is allowed to compose of J analyses. We show that the design controls the familywise error rate in the strong sense and illustrate the method through an example and simulation. We find that the design is robust to misspecification of the correlation between the endpoints and requires similar numbers of subjects to a trial based on efficacy alone for moderately correlated endpoints.
Thomas Jaki - One of the best experts on this subject based on the ideXlab platform.
-
designing multi arm multi stage clinical trials using a risk Benefit Criterion for treatment selection
Statistics in Medicine, 2016Co-Authors: Thomas Jaki, Lisa V HampsonAbstract:Multi-arm clinical trials that compare several active treatments to a common control have been proposed as an efficient means of making an informed decision about which of several treatments should be evaluated further in a confirmatory study. Additional efficiency is gained by incorporating interim analyses and, in particular, seamless Phase II/III designs have been the focus of recent research. Common to much of this work is the constraint that selection and formal testing should be based on a single efficacy endpoint, despite the fact that in practice, safety considerations will often play a central role in determining selection decisions. Here, we develop a multi-arm multi-stage design for a trial with an efficacy and safety endpoint. The safety endpoint is explicitly considered in the formulation of the problem, selection of experimental arm and hypothesis testing. The design extends group-sequential ideas and considers the scenario where a minimal safety requirement is to be fulfilled and the treatment yielding the best combined safety and efficacy trade-off satisfying this constraint is selected for further testing. The treatment with the best trade-off is selected at the first interim analysis, while the whole trial is allowed to compose of J analyses. We show that the design controls the familywise error rate in the strong sense and illustrate the method through an example and simulation. We find that the design is robust to misspecification of the correlation between the endpoints and requires similar numbers of subjects to a trial based on efficacy alone for moderately correlated endpoints. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
-
designing multi arm multi stage clinical trials using a risk Benefit Criterion for treatment selection
Statistics in Medicine, 2016Co-Authors: Thomas Jaki, Lisa V HampsonAbstract:Multi-arm clinical trials that compare several active treatments to a common control have been proposed as an efficient means of making an informed decision about which of several treatments should be evaluated further in a confirmatory study. Additional efficiency is gained by incorporating interim analyses and, in particular, seamless Phase II/III designs have been the focus of recent research. Common to much of this work is the constraint that selection and formal testing should be based on a single efficacy endpoint, despite the fact that in practice, safety considerations will often play a central role in determining selection decisions. Here, we develop a multi-arm multi-stage design for a trial with an efficacy and safety endpoint. The safety endpoint is explicitly considered in the formulation of the problem, selection of experimental arm and hypothesis testing. The design extends group-sequential ideas and considers the scenario where a minimal safety requirement is to be fulfilled and the treatment yielding the best combined safety and efficacy trade-off satisfying this constraint is selected for further testing. The treatment with the best trade-off is selected at the first interim analysis, while the whole trial is allowed to compose of J analyses. We show that the design controls the familywise error rate in the strong sense and illustrate the method through an example and simulation. We find that the design is robust to misspecification of the correlation between the endpoints and requires similar numbers of subjects to a trial based on efficacy alone for moderately correlated endpoints.
Robert J Brent - One of the best experts on this subject based on the ideXlab platform.
-
a social cost Benefit Criterion for evaluating voluntary counseling and testing with an application to tanzania
Health Economics, 2010Co-Authors: Robert J BrentAbstract:Rationale: There are many interventions for HIV/AIDS that require that people know their status and hence require a HIV test. Testing that is driven by a desire to prevent the spread of the disease often has an indirect effect on others. These external effects need to be identified, quantified and included as part of the Benefits and costs of testing. Pioneering analyses of HIV testing by Philipson and Posner have introduced the economic calculus of individual expected Benefits and costs of activities into an understanding of the HIV epidemic. What is required for social evaluations is an extension of the analysis to ensure that external effects are included. Objectives: The objective of this paper is two-fold. First we seek to formulate cost–Benefit criteria that incorporate fully the external effects in the evaluation of Voluntary Counseling and Testing (VCT). We achieve this by recasting the individual calculus of Benefits and costs to a couple setting. We can then compare an individual's cost–Benefit analysis of being tested with social criteria that look at outcomes from a couple's perspective for both separate and dual/joint testing. Second we aim to apply our social criteria to VCT programs as they currently operate in Tanzania and how these programs might operate in the future when they are scaled up to relate to the general population. Methodology: We develop social criteria for evaluating separate and dual VCT using a couple's perspective with and without altruism. Therefore, the welfare function is based on two individual expected utility functions viewed as a couple, either married or regular partners. The Benefits are the averted lives lost whenever discordant couples are revealed. The costs of VCT are the Benefits of unprotected sex that the couple foregoes and the costs of the testing and counseling. The cost–Benefit criteria are applied to VCT programs in Tanzania. The four main ingredients estimated are: the foregone Benefit of unprotected sex (measured by the compensated wage differentials charged by commercial sex workers); the probability of infection; the cost of an infection (measured by both the value of a statistical life and the human capital approaches) and the cost of a single test (which includes behavior-modifying counseling). Conclusions: We find separate testing in existing VCT programs to be only marginally worthwhile. However, in scaled-up programs the Benefit–cost ratio is over three. Dual testing is always more beneficial than separate testing. However, this advantage is reduced in scaled-up programs. VCT should be greatly expanded throughout Tanzania as future returns would be even higher for both separate and joint counseling and HIV testing. Copyright © 2009 John Wiley & Sons, Ltd.
-
a social cost Benefit Criterion for evaluating voluntary counseling and testing with an application to tanzania
2007Co-Authors: Robert J BrentAbstract:Rationale: There are many interventions for HIV/AIDS that require that people know their status and hence require a HIV test. Testing that is motivated by a desire to receive treatment need not directly affect others. However, testing that is driven by a desire to prevent the spread of the disease often has an indirect effect on others, whether they be sex partners, babies of infected mothers or recipients of blood transfusions. These external effects need to be identified, quantified and included as part of the Benefits and costs of testing. Pioneering analyses of HIV testing by Philipson and Posner have introduced the economic calculus of individual expected Benefits and costs of activities into an understanding of the HIV epidemic. What is required for social evaluations is an extension of the analysis to ensure that external effects are included. Objectives: The objective of this paper is two-fold. First we seek to formulate cost-Benefit criteria that incorporate fully the external effects in the evaluation of Voluntary Counseling and Testing (VCT). We achieve this by recasting the individual calculus of Benefits and costs to a couples setting. We can then compare an individual's cost-Benefit analysis of being tested with social criteria that look at outcomes from a couple's perspective for both separate and dual / joint testing. Second we aim to apply our social criteria to VCT programs as they currently operate in Tanzania and how these programs might operate in the future when they are scaled-up to relate to the general population. Methodology: We develop social criteria for evaluating separate and dual VCT using a couples' perspective. So the welfare function is based on two individual expected utility functions viewed as a couple, either married or regular partners. The Benefits are the averted lives lost whenever discordant couples are revealed. The costs of VCT are the Benefits of unprotected sex that the couple foregoes and the costs of the testing and counseling. The cost-Benefit criteria are applied to VCT programs in Tanzania. The four main ingredients estimated are: the foregone Benefit of unprotected sex (measured by the compensated wage differentials charged by commercial sex workers); the probability of infection; the cost of an infection (measured by both the value of a statistical life and the human capital approaches) and the cost of a single test. Conclusions: We find separate testing in existing VCT programs only marginally worthwhile. However, in scaled-up programs (where the probability of infection is related to the general population and not just the current sample of persons in the VCT program) the Benefit-cost ratio is over three. Dual testing is always more beneficial than separate testing. However, this advantage is reduced in scaled-up programs. So the policy conclusion that follows from our application of cost-Benefit analysis to VCT in Tanzania is that although the existing program is marginally worthwhile, VCT should be greatly expanded throughout Tanzania as future returns would be even higher for both separate and joint counseling and HIV testing.
Robert C Lind - One of the best experts on this subject based on the ideXlab platform.
-
intergenerational equity discounting and the role of cost Benefit analysis in evaluating global climate policy
Energy Policy, 1995Co-Authors: Robert C LindAbstract:When public policies with impacts far into the future are being debated, the question inevitably is raised whether cost-Benefit analysis which discounts future costs and Benefits is not biased against future generations and whether, if such discounting is appropriate at all, a lower rate should be used to avoid such bias. The debate on global climate change is no exception. This paper sketches and analyses the welfare foundations of cost-Benefit analysis and from this perspective analyses the role of cost-Benefit analysis in the climate policy debate, particularly with reference to intergenerational effects. The paper concludes that the cost-Benefit Criterion cannot provide a definitive basis for deciding whether we should commit to a longer-term programme to moderate climate change; the issues of intergenerational equity are not that global climate change will significantly lower the GNP of future generations, but relate to the possibility of science fiction-like changes in the planet that will produce catastrophic effects in the future; and the typical way in which the cost-Benefit problem is posed obscures the basic choices that we should be evaluating.
P J Fish - One of the best experts on this subject based on the ideXlab platform.
-
cost Benefit Criterion for selection of pulsed doppler ultrasound spectral mean frequency and bandwidth estimators
IEEE Transactions on Biomedical Engineering, 1993Co-Authors: M G Ruano, P J FishAbstract:A flexible selection Criterion for spectral estimators based on the weighted statistical accuracy (Benefit) of estimation of decisive spectral parameters under the constraint of low computational complexity (cost) is proposed. This new cost/Benefit Criterion also selects the model order for parametric spectral estimators-selecting model orders significantly lower than those determined by accepted criteria. The importance of different Doppler signal parameters (e.g., mean frequency and spectral bandwidth) and their accuracy of estimation is incorporated by the use of weighting factors. The use of this method with simulated Doppler signals led to the selection of the modified covariance Alt estimator. >