GREMA - Grup de Recerca en Estadística Matemàtica i les seves Aplicacions
http://hdl.handle.net/2117/3387
2016-02-13T06:50:46ZExtension of the asymptotic relative efficiency method to select the primary endpoint in a randomized clinical trial
http://hdl.handle.net/2117/26456
Extension of the asymptotic relative efficiency method to select the primary endpoint in a randomized clinical trial
Plana-Ripoll, Oleguer; Gómez Melis, Guadalupe
We extend the ARE method proposed in Gómez and Lagakos (2013) devised to decide which primary endpoint to choose when comparing two treatments in a randomized clinical trial. The ARE method is
based on the Asymptotic Relative Efficiency (ARE) between two logrank tests to compare two treatments: one is based on a relevant endpoint E1 while the other is based on a composite endpoint E* = E1 ¿ E2, where E2 is an additional endpoint. The ARE depends, besides some intuitive parameters, on the joint law of the times T1 and T2 from randomization to E1 and E2, respectively. Gómez and Lagakos (2013) characterize this joint law by means of Frank’s copula. In our work, several families of copulas can be chosen for the bivariate survival function of (T1, T2) so that different dependence struc- tures between T1 and T2 are feasible. We motivate the problem and show how to apply the method through a real cardiovascular clinical trial. We explore the influence of the
copula chosen into the ARE value by means of a simulation study. We conclude that the recommendation on whether or not to use
the composite endpoint as the primary endpoint for the investigation is, almost always, independent of the copula chosen.
2015-02-20T18:40:25ZPlana-Ripoll, OleguerGómez Melis, GuadalupeWe extend the ARE method proposed in Gómez and Lagakos (2013) devised to decide which primary endpoint to choose when comparing two treatments in a randomized clinical trial. The ARE method is
based on the Asymptotic Relative Efficiency (ARE) between two logrank tests to compare two treatments: one is based on a relevant endpoint E1 while the other is based on a composite endpoint E* = E1 ¿ E2, where E2 is an additional endpoint. The ARE depends, besides some intuitive parameters, on the joint law of the times T1 and T2 from randomization to E1 and E2, respectively. Gómez and Lagakos (2013) characterize this joint law by means of Frank’s copula. In our work, several families of copulas can be chosen for the bivariate survival function of (T1, T2) so that different dependence struc- tures between T1 and T2 are feasible. We motivate the problem and show how to apply the method through a real cardiovascular clinical trial. We explore the influence of the
copula chosen into the ARE value by means of a simulation study. We conclude that the recommendation on whether or not to use
the composite endpoint as the primary endpoint for the investigation is, almost always, independent of the copula chosen.Developing professional skills at tertiary level: A model to integrate competencies across the curriculum
http://hdl.handle.net/2117/25103
Developing professional skills at tertiary level: A model to integrate competencies across the curriculum
Sánchez Carracedo, Fermín; Soler Cervera, Antonia; López Álvarez, David; Martín Escofet, Carme; Ageno Pulido, Alicia; Belanche Muñoz, Luis Antonio; Cabré Garcia, José M.; Cobo Valeri, Erik; Farré Cirera, Rafael; García Almiñana, Jordi; Marès Martí, Pere
In the context of the European Higher Education Area, curriculum design needs to be based on the defined competencies of each degree programs, including both domain specific and professional competencies. In this educational context, developing students’ professional skills poses a new challenge we need to face. The present work proposes a model to globally develop professional skills in an Engineering degree program. Based on competency maps, this model allows careful analysis, revision and iteration for an effective integration of professional skills. We define each competency in terms of “dimensions” (or sub-skills), which are further defined according to three-level objectives. Competency maps are built showing the specific graded objectives, which allows to integrate them most finely into degree subjects. A global competency map is also designed including the objectives to be achieved throughout the degree. This global map becomes a useful tool for curriculum designers and coordinators. It allows them to optimize the workload, and to make adjustments most effectively, helping students develop the defined competencies as a global comprehensive experience. To illustrate our model, we explain how it has been implemented to integrate “Communication skills” into subjects, and how the model has been applied to assess “Appropriate attitude towards work” skills.
2014-12-19T10:26:59ZSánchez Carracedo, FermínSoler Cervera, AntoniaLópez Álvarez, DavidMartín Escofet, CarmeAgeno Pulido, AliciaBelanche Muñoz, Luis AntonioCabré Garcia, José M.Cobo Valeri, ErikFarré Cirera, RafaelGarcía Almiñana, JordiMarès Martí, PereIn the context of the European Higher Education Area, curriculum design needs to be based on the defined competencies of each degree programs, including both domain specific and professional competencies. In this educational context, developing students’ professional skills poses a new challenge we need to face. The present work proposes a model to globally develop professional skills in an Engineering degree program. Based on competency maps, this model allows careful analysis, revision and iteration for an effective integration of professional skills. We define each competency in terms of “dimensions” (or sub-skills), which are further defined according to three-level objectives. Competency maps are built showing the specific graded objectives, which allows to integrate them most finely into degree subjects. A global competency map is also designed including the objectives to be achieved throughout the degree. This global map becomes a useful tool for curriculum designers and coordinators. It allows them to optimize the workload, and to make adjustments most effectively, helping students develop the defined competencies as a global comprehensive experience. To illustrate our model, we explain how it has been implemented to integrate “Communication skills” into subjects, and how the model has been applied to assess “Appropriate attitude towards work” skills.Effect of changing the copular when choosing the primary endpoint in a Randomized Clinical Trial
http://hdl.handle.net/2117/24709
Effect of changing the copular when choosing the primary endpoint in a Randomized Clinical Trial
Plana Ripoll, Oleguer; Gómez Melis, Guadalupe
2014-11-12T18:44:12ZPlana Ripoll, OleguerGómez Melis, GuadalupeRandomised study to assess the efficacy and safety of once-daily etravirine-based regimen as a switching strategy in HIV-infected patients receiving a protease inhibitor-containing regimen. Etraswitch study
http://hdl.handle.net/2117/22665
Randomised study to assess the efficacy and safety of once-daily etravirine-based regimen as a switching strategy in HIV-infected patients receiving a protease inhibitor-containing regimen. Etraswitch study
Echeverria, Patricia; Bonjoch, Anna; Puig Batalla, Jorge; Molto, Jose; Paredes, Roger; Sirera, Guillem; Ornelas, Arelly; Pérez Álvarez, Nuria; Clotet, Bonaventura; Negredo, Eugènia
Background: Etravirine (ETR) was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naive patients. However, data on the switching from protease inhibitors (PI) to ETR are lacking.; Methods: HIV-1-infected patients with suppressed viral load (VL) during a PI-containing regimen (>12 months) and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water) (ETR group, n = 22) or to continue with the same regimen (control group, n = 21). Percentage of patients with VL <= 50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile.; Results: We included 43 patients [72.9% male, 46.3 (42.2; 50.6) years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation) and another in the control group (simplification) discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL); treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure) (p = 0.58). CD4+ T-cell counts did not significantly vary [+49 cells/mu L in the ETR group (p = 0.25) and -4 cells/mu L in the control group (p = 0.71)]. The ETR group showed significant reductions in cholesterol (p<0.001), triglycerides (p=<0.001), and glycemia (p = 0.03) and higher satisfaction (0-10 scale) (p = 0.04). Trough plasma concentrations of ETR were similar to observed in studies using ETR twice daily.; Conclusion: Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly.
2014-04-23T10:44:16ZEcheverria, PatriciaBonjoch, AnnaPuig Batalla, JorgeMolto, JoseParedes, RogerSirera, GuillemOrnelas, ArellyPérez Álvarez, NuriaClotet, BonaventuraNegredo, EugèniaBackground: Etravirine (ETR) was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naive patients. However, data on the switching from protease inhibitors (PI) to ETR are lacking.; Methods: HIV-1-infected patients with suppressed viral load (VL) during a PI-containing regimen (>12 months) and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water) (ETR group, n = 22) or to continue with the same regimen (control group, n = 21). Percentage of patients with VL <= 50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile.; Results: We included 43 patients [72.9% male, 46.3 (42.2; 50.6) years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation) and another in the control group (simplification) discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL); treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure) (p = 0.58). CD4+ T-cell counts did not significantly vary [+49 cells/mu L in the ETR group (p = 0.25) and -4 cells/mu L in the control group (p = 0.71)]. The ETR group showed significant reductions in cholesterol (p<0.001), triglycerides (p=<0.001), and glycemia (p = 0.03) and higher satisfaction (0-10 scale) (p = 0.04). Trough plasma concentrations of ETR were similar to observed in studies using ETR twice daily.; Conclusion: Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly.Some theoretical thoughts when using a composite endpoint to prove the efficacy of a treatment
http://hdl.handle.net/2117/22571
Some theoretical thoughts when using a composite endpoint to prove the efficacy of a treatment
Gómez Melis, Guadalupe
This paper discusses, following Gómez and Lagakos (2011) methodology, to what extent is there a gain in efficiency from adding a component event to a relevant endpoint when the treatment effect on this component is not as strong as on the original relevant endpoint under ideal (independence) circumstances. It presents the bivariate copula model used to overcome the independence assumption and presents the relationship between the components of the asymptotic relative efficiency and a set of interpretable parametres.
2014-04-08T16:25:26ZGómez Melis, GuadalupeThis paper discusses, following Gómez and Lagakos (2011) methodology, to what extent is there a gain in efficiency from adding a component event to a relevant endpoint when the treatment effect on this component is not as strong as on the original relevant endpoint under ideal (independence) circumstances. It presents the bivariate copula model used to overcome the independence assumption and presents the relationship between the components of the asymptotic relative efficiency and a set of interpretable parametres.On left-truncating and mixing poisson distributions
http://hdl.handle.net/2117/22548
On left-truncating and mixing poisson distributions
Valero Baya, Jordi; Pérez Casany, Marta; Ginebra Molins, Josep
The distributions obtained by left-truncating at k a mixed Poisson distribution, kT-MP, and those obtained by mixing previously left-truncated Poisson distributions, M-kTP, are characterized by means of their probability generating function. The main consequence is that every kT-MP distribution is a M-kTP distribution, but not the other way around.
2014-04-07T17:26:00ZValero Baya, JordiPérez Casany, MartaGinebra Molins, JosepThe distributions obtained by left-truncating at k a mixed Poisson distribution, kT-MP, and those obtained by mixing previously left-truncated Poisson distributions, M-kTP, are characterized by means of their probability generating function. The main consequence is that every kT-MP distribution is a M-kTP distribution, but not the other way around.Review of multivariate survival data
http://hdl.handle.net/2117/22543
Review of multivariate survival data
Gómez Melis, Guadalupe; Calle Rosingana, M. Luz; Serrat Piè, Carles; Espinal Berenguer, Anna
This paper reviews some of the main contributions in the area of multivariate survival data and proposes some possible extensions. In particular, we have concentrated our search and study on those papers that are relevant to the situation where two (or more) consecutive variables are followed until a common day of analysis and subject to informative censoring.
The paper reviews bivariate nonparametric approaches and extend some of them to the case of two nonconsecutive times. We introduce the notation and construct the likelihood for the general problem of more than two consecutive survival times. We formulate the time dependencies and trends via a Bayesian approach. Finally, three regression models for multivariate survival times are discussed together with the differences among them which will be useful when the main interest is on the effect of covariates on the risk of failure.
Document de recerca publicat per la UPC. Departament d'Estadística i Investigació operativa
2014-04-07T14:05:21ZGómez Melis, GuadalupeCalle Rosingana, M. LuzSerrat Piè, CarlesEspinal Berenguer, AnnaThis paper reviews some of the main contributions in the area of multivariate survival data and proposes some possible extensions. In particular, we have concentrated our search and study on those papers that are relevant to the situation where two (or more) consecutive variables are followed until a common day of analysis and subject to informative censoring.
The paper reviews bivariate nonparametric approaches and extend some of them to the case of two nonconsecutive times. We introduce the notation and construct the likelihood for the general problem of more than two consecutive survival times. We formulate the time dependencies and trends via a Bayesian approach. Finally, three regression models for multivariate survival times are discussed together with the differences among them which will be useful when the main interest is on the effect of covariates on the risk of failure.Joint modelling analysis of prostate cancer incidence: frequentist and bayesian approaches
http://hdl.handle.net/2117/22507
Joint modelling analysis of prostate cancer incidence: frequentist and bayesian approaches
Piulachs, Xavier; Serrat Piè, Carles; Rué, Montserrat; Armero, Carmen; Forte, Anabel; Perpiñán, Héctor; Luján, Marcos; Páez, Álvaro
Prostate specific antigen (PSA) is a biomarker for prostate cancer (PCa) that is widely used for PCa screening. Using a database of 2415 men included in the Spanish screening arm of the ERSPC Study, we will use joint modelling strategies to analyze if longitudinal PSA profiles and time to PCa incidence allow to obtain a better estimate of the individual risk of PCa. Conclusions and limitations of the study will be discussed.
2014-04-03T15:38:32ZPiulachs, XavierSerrat Piè, CarlesRué, MontserratArmero, CarmenForte, AnabelPerpiñán, HéctorLuján, MarcosPáez, ÁlvaroProstate specific antigen (PSA) is a biomarker for prostate cancer (PCa) that is widely used for PCa screening. Using a database of 2415 men included in the Spanish screening arm of the ERSPC Study, we will use joint modelling strategies to analyze if longitudinal PSA profiles and time to PCa incidence allow to obtain a better estimate of the individual risk of PCa. Conclusions and limitations of the study will be discussed.Estimation of survival functions subject to order restrictions
http://hdl.handle.net/2117/22506
Estimation of survival functions subject to order restrictions
Serrat Piè, Carles; Moreno, Laura
This contribution is framed in, and is part of, the Durabiltiy of Building Facades studies carried out in the last decade in the Institut d’Estadística i Matemàtica Aplicada a l’Edificació and Laboratori d’ Edificació at the Universitat Politècnica de Catalunya. The goal of this presentation is to incorporate in the analysis of the estimation of the durability of building facades respect the severity degrees (low, medium or high) the order of the events of interest. In other words, we will take into account preliminary estimates of the survival probabilities of previous events (e.g. initial severities) as order constraints for the estimation of survival probabilities for subsequent events of interest (e.g. more advanced severities).
Standard statistical analyses for this type of interval censored data are usually conducted by using the R statistical software, however it does not include libraries or packages neither for simultaneous estimation nor for the use of order constraints. For this reason, we will use AMPL and the solver SNOPT to implement the Turnbull's estimator with order restrictions, for the estimation of the survival function of each event of interest taking into account the information given by the survival function of some previous event of interest. The proposed methodology solves the inconsistency problem associated with a separate estimation of the respective survival probabilities. As a illustration the methodology will be applied to a simulated dataset. As a theoretical contribution, a conjecture on Turnbull's estimator Theorem under order restrictions will be proposed.
2014-04-03T15:05:09ZSerrat Piè, CarlesMoreno, LauraThis contribution is framed in, and is part of, the Durabiltiy of Building Facades studies carried out in the last decade in the Institut d’Estadística i Matemàtica Aplicada a l’Edificació and Laboratori d’ Edificació at the Universitat Politècnica de Catalunya. The goal of this presentation is to incorporate in the analysis of the estimation of the durability of building facades respect the severity degrees (low, medium or high) the order of the events of interest. In other words, we will take into account preliminary estimates of the survival probabilities of previous events (e.g. initial severities) as order constraints for the estimation of survival probabilities for subsequent events of interest (e.g. more advanced severities).
Standard statistical analyses for this type of interval censored data are usually conducted by using the R statistical software, however it does not include libraries or packages neither for simultaneous estimation nor for the use of order constraints. For this reason, we will use AMPL and the solver SNOPT to implement the Turnbull's estimator with order restrictions, for the estimation of the survival function of each event of interest taking into account the information given by the survival function of some previous event of interest. The proposed methodology solves the inconsistency problem associated with a separate estimation of the respective survival probabilities. As a illustration the methodology will be applied to a simulated dataset. As a theoretical contribution, a conjecture on Turnbull's estimator Theorem under order restrictions will be proposed.Longitudinal + reliability = joint modeling
http://hdl.handle.net/2117/22505
Longitudinal + reliability = joint modeling
Serrat Piè, Carles
The aim of this presentation is to introduce joint modelling techniques for the simultaneous analysis of longitudinal time-varying data and time-to-event data. This is an increasing area of interest for the analysis of complex systems. Among others, three main advantages of this approach are: a) it corrects the bias derived from a traditional separate analysis, b) the modelization allows to incorporate and model the between and within correlation among observations and, c) true longitudinal profiles for endogenous covariates can be included in the relative hazard survival sub-model.
The relevant benefit of these models is being able to estimate the effect of each subject-specific longitudinal profile in the hazard function for the event of interest, in an adaptive manner. In particular, subject-specific dynamic predictions, like conditional survival functions given the available longitudinal information, can be derived. In order to implement joint models, existing open source libraries in R will be introduced and some illustrations will be given.
2014-04-03T14:50:15ZSerrat Piè, CarlesThe aim of this presentation is to introduce joint modelling techniques for the simultaneous analysis of longitudinal time-varying data and time-to-event data. This is an increasing area of interest for the analysis of complex systems. Among others, three main advantages of this approach are: a) it corrects the bias derived from a traditional separate analysis, b) the modelization allows to incorporate and model the between and within correlation among observations and, c) true longitudinal profiles for endogenous covariates can be included in the relative hazard survival sub-model.
The relevant benefit of these models is being able to estimate the effect of each subject-specific longitudinal profile in the hazard function for the event of interest, in an adaptive manner. In particular, subject-specific dynamic predictions, like conditional survival functions given the available longitudinal information, can be derived. In order to implement joint models, existing open source libraries in R will be introduced and some illustrations will be given.