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PubMed2002

Sensitivity analysis and auto-calibration of an integral dynamic model for river water quality.

ESWAT--Extended Soil and Water Assessment Tool--was developed to allow for an integral modelling of the water quantity and quality processes in river basins. ESWAT is a physically based, semi-distributed model, with a moderate-to-large number of parameters and input and output variables (depending on the desegregation scheme). An auto-calibration procedure was implemented for the optimisation of the process parameters. The procedure is based on a new approach for multi-objective calibration and incorporates the algorithms of the Shuffled Complex Evolution Method. The optimisation uses a global optimisation criterion, whereby several output variables can be taken into account simultaneously. A statistical method enables the aggregation of the objective functions for individual variables, hereby avoiding the weighting problem. To select the important parameters for the optimisation, a sensitivity analysis precedes the calibration. The latter analysis is based on the One-factor-At-a-Time (OAT) design approach. The sensitivity analysis and the calibration procedure are applied to the river Dender in Belgium. The river is characterised by high pollution loads and long residence times in summer periods.

Calibration↗
PubMed2005

Mathematical models use varying parameter strategies to represent paralyzed muscle force properties: a sensitivity analysis.

BACKGROUND: Mathematical muscle models may be useful for the determination of appropriate musculoskeletal stresses that will safely maintain the integrity of muscle and bone following spinal cord injury. Several models have been proposed to represent paralyzed muscle, but there have not been any systematic comparisons of modelling approaches to better understand the relationships between model parameters and muscle contractile properties. This sensitivity analysis of simulated muscle forces using three currently available mathematical models provides insight into the differences in modelling strategies as well as any direct parameter associations with simulated muscle force properties. METHODS: Three mathematical muscle models were compared: a traditional linear model with 3 parameters and two contemporary nonlinear models each with 6 parameters. Simulated muscle forces were calculated for two stimulation patterns (constant frequency and initial doublet trains) at three frequencies (5, 10, and 20 Hz). A sensitivity analysis of each model was performed by altering a single parameter through a range of 8 values, while the remaining parameters were kept at baseline values. Specific simulated force characteristics were determined for each stimulation pattern and each parameter increment. Significant parameter influences for each simulated force property were determined using ANOVA and Tukey's follow-up tests (alpha <or= 0.05), and compared to previously reported parameter definitions. RESULTS: Each of the 3 linear model's parameters most clearly influence either simulated force magnitude or speed properties, consistent with previous parameter definitions. The nonlinear models' parameters displayed greater redundancy between force magnitude and speed properties. Further, previous parameter definitions for one of the nonlinear models were consistently supported, while the other was only partially supported by this analysis. CONCLUSION: These three mathematical models use substantially different strategies to represent simulated muscle force. The two contemporary nonlinear models' parameters have the least distinct associations with simulated muscle force properties, and the greatest parameter role redundancy compared to the traditional linear model.

Journal Article↗
PubMedDate not supplied

Sensitivity analysis in economic evaluation: a review of published studies.

A structured methodological review of journal articles published in 1992 was undertaken to determine whether recently published economic evaluation studies deal systematically and comprehensively with uncertainty. Ninety three journal articles were identified from a range of searches including a computerised search of the MEDLINE CD-Rom database. Articles were reviewed to determine how they had handled uncertainty in: a) data sources; b) generalisability; c) extrapolation; and d) analytic method. Articles were subsequently assessed to determine how they had represented this uncertainty in terms of the overall results of their analysis. Finally, studies were rated on the basis of their overall performance with respect to dealing systematically and comprehensively with uncertainty. Despite the numerous books and articles devoted to the appropriate methods to be employed by analysts conducting economic evaluation, 22 (24%) studies failed to consider uncertainty at all and 35 (38%) studies employed sensitivity analysis in a manner judged as inadequate. In all, 36 (39%) studies were judged to have given at least an adequate account of uncertainty with 13 (14%) of those judged to have provided a good account of uncertainty. Such disappointing results may reflect a general lack of detail in much of the methods literature concerning how sensitivity analysis should be applied and how results should be presented. Journal editors and readers of economic evaluation articles should acquaint themselves with the methods for handling uncertainty in order that they can critically evaluate the extent to which authors have allowed for uncertainties inherent in their analysis.

Cost-Benefit Analysis↗
PubMed2005

Can Cochrane Reviews in controversial areas be biased? A sensitivity analysis based on the protocol of a Systematic Cochrane Review on low-level laser therapy in osteoarthritis.

OBJECTIVE: The aim of this study was to test if a conclusion in a systematic review of low-level laser therapy (LLLT) for osteoarthritis from the Cochrane Library was valid and robust. BACKGROUND DATA: Health policy decisions often rely on conclusions from the Cochrane Database of Systematic Reviews for approval of new therapies, although their validity for controversial non-pharmacological treatment has been questioned. METHODS: Validity was tested against a nine-item checklist for systematic reviews. Review selections were analyzed for possible discrepancies between trial and review reports, and omissions of relevant trials and data. Alternative data from discrepancies and omissions were then imputed in a sensitivity analysis, to test if review conclusions were robust. RESULTS: Only clinicians who had performed LLLT trials with negative results were invited into the review group. Review quality was sound in areas of literature search and methodological assessments, and some of the limitations were mentioned. The statistical analysis held 18 questionable selections such as omissions of trials, data, and subgroup analyses. These selections systematically favored the negative review conclusion. Without altering the review protocol, the sensitivity analysis of combined results changed to significantly positive for continuous and categorical data when data from all included trials were combined. Further sensitivity analyses with inclusion of valid non-included trials, performance of missing follow-up, and subgroup analyses revealed consistent and highly significant results in favor of active LLLT. CONCLUSIONS: In this example, the Cochrane review conclusion was neither robust nor valid. Representation of experts and different views on efficacy in the review group and extensive use of sensitivity analyses could probably improve quality control of reviews in areas of controversy.

Bias↗
PubMed1996

Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma.

UNLABELLED: Preliminary studies have shown that PET is more accurate than CT for the staging of non-small-cell lung carcinoma (NSCLC). However, the potential effect of PET on the management of these patients and its cost-effectiveness has not been rigorously studied. Thus, we have used decision tree sensitivity analysis to assess the cost-effectiveness of a PET based strategy for staging of NSCLC. METHODS: Two decision strategies for selection of potential surgical candidates were compared; thoracic CT alone or thoracic CT and thoracic PET. The first decision tree was conservatively constructed by requiring mediastinoscopy (biopsy) to confirm imaging results so that no patient with surgically curable disease would miss the opportunity for surgery in either strategy. A second less conservative tree in which only nonconcordant results are biopsied was also tested. The various paths of each strategy are dependent on numerous parameters which were determined from a review of the medical literature. Life expectancy was calculated using the declining exponential approximation of life expectancy and reduced based on procedural mortality. Costs were based on mean costs at our institution. For all possible outcomes of each strategy, the expected cost and projected life expectancy were determined. The effect of changing one or more parameters on the expected cost and life expectancy were studied using a sensitivity analysis. RESULTS: The CT + PET strategy in the conservative decision tree showed a saving of $1154 per patient without a loss of life expectancy (increase of 2.96 days) as compared to the alternate strategy of CT alone. Both these effects were the result of improved staging of lung carcinoma prior to the decision for surgery. The CT + PET strategy in the less conservative decision tree showed a savings of $2267 per patient but misses 1.7% of potentially operable patients. CONCLUSION: These results show through rigorous decision tree analysis, the potential cost-effectiveness of using FDG PET in the management of NSCLC. These results form a basis for detailed study of the results obtained from multicenter trials on the accuracy of PET in NSCLC management. Furthermore, the techniques utilized for decision tree analysis have broad range of applicability to the entire field of nuclear medicine.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Method for sensitivity analysis of photonic crystal devices.

We present a new method for sensitivity analysis of photonic crystal devices. The algorithm is based on a finite-difference frequency-domain model and uses the adjoint variable method and perturbation theory techniques. We show that our method is highly efficient and accurate and can be applied to calculation of the sensitivity of transmission parameters of resonant nanophotonic devices.

Journal Article↗
PubMed1998

Economic modeling and sensitivity analysis.

The field of pharmacoeconomics (PE) faces serious concerns of research credibility and bias. The failure of researchers to reproduce similar results in similar settings, the inappropriate use of clinical data in economic models, the lack of transparency, and the inability of readers to make meaningful comparisons across published studies have greatly contributed to skepticism about the validity, reliability, and relevance of these studies to healthcare decision-makers. Using a case study in the field of lipid PE, two suggestions are presented for generally applicable reporting standards that will improve the credibility of PE. Health economists and researchers should be expected to provide either the software used to create their PE model or a multivariate sensitivity analysis of their PE model. Software distribution would allow other users to validate the assumptions and calculations of a particular model and apply it to their own circumstances. Multivariate sensitivity analysis can also be used to present results in a consistent and meaningful way that will facilitate comparisons across the PE literature. Using these methods, broader acceptance and application of PE results by policy-makers would become possible. To reduce the uncertainty about what is being accomplished with PE studies, it is recommended that these guidelines become requirements of both scientific journals and healthcare plan decision-makers. The standardization of economic modeling in this manner will increase the acceptability of pharmacoeconomics as a practical, real-world science.

Journal Article↗
PubMed1999

Monte Carlo sensitivity analysis of unknown parameters in hazardous materials transportation risk assessment.

The US Department of Transportation was interested in the risks associated with transporting Hydrazine in tanks with and without relief devices. Hydrazine is both highly toxic and flammable, as well as corrosive. Consequently, there was a conflict as to whether a relief device should be used or not. Data were not available on the impact of relief devices on release probabilities or the impact of Hydrazine on the likelihood of fires and explosions. In this paper, a Monte Carlo sensitivity analysis of the unknown parameters was used to assess the risks associated with highway transport of Hydrazine. To help determine whether or not relief devices should be used, fault trees and event trees were used to model the sequences of events that could lead to adverse consequences during transport of Hydrazine. The event probabilities in the event trees were derived as functions of the parameters whose effects were not known. The impacts of these parameters on the risk of toxic exposures, fires, and explosions were analyzed through a Monte Carlo sensitivity analysis and analyzed statistically through an analysis of variance. The analysis allowed the determination of which of the unknown parameters had a significant impact on the risks. It also provided the necessary support to a critical transportation decision even though the values of several key parameters were not known.

Hazardous Substances↗
PubMed2000

Head-neck finite element model for motor vehicle inertial impact: material sensitivity analysis.

The aim of this study was to conduct a material sensitivity analysis using a head-neck finite element model (FEM). The model included the skull, C1-T1 vertebrae, intervertebral discs, facet joints, and biomechanically relevant ligaments. Poisson's ratio and elastic modulus of the head-neck components were varied. The loading condition included the impact load applied to the first thoracic vertebra. Commercially available software (LS-DYNA) was used for the analysis. Head angle versus time, head center of gravity trajectory, and head center of gravity angular acceleration responses were computed. In general, the variation of elastic modulus had a higher effect on the response compared to variation of Poisson's ratio. As the elastic modulus was increased, the head angle and angular acceleration increased. The present findings form a first step in the study of computational biomechanics of vehicular-related trauma.

Acceleration↗
PubMed2001

Methods for conducting sensitivity analysis of trials with potentially nonignorable competing causes of censoring.

We consider inference for the treatment-arm mean difference of an outcome that would have been measured at the end of a randomized follow-up study if, during the course of the study, patients had not initiated a nonrandomized therapy or dropped out. We argue that the treatment-arm mean difference is not identified unless unverifiable assumptions are made. We describe identifying assumptions that are tantamount to postulating relationships between the components of a pattern-mixture model but that can also be interpreted as imposing restrictions on the cause-specific censoring probabilities of a selection model. We then argue that, although sufficient for identification, these assumptions are insufficient for inference due to the curse of dimensionality. We propose reducing dimensionality by specifying semiparametric cause-specific selection models. These models are useful for conducting a sensitivity analysis to examine how inference for the treatment-arm mean difference changes as one varies the magnitude of the cause-specific selection bias over a plausible range. We provide methodology for conducting such sensitivity analysis and illustrate our methods with an analysis of data from the AIDS Clinical Trial Group (ACTG) study 002.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A sensitivity analysis of secular trends in risk factors and mortality based on cohort studies.

Because of a "healthy responder effect," secular trends in mortality based on cohort studies may be biased if based on responders only. Because responders are selected on the basis of their health at study entry, subjects just entering a study are not comparable with subjects who have been in the study for several years. The result may be an artificial increase in mortality, which impedes analyzing the effect of secular trends in risk factors on mortality. The objective of this paper is to suggest a solution by using data on nonresponders and applying a sensitivity analysis. We illustrate this solution with data on trends in smoking prevalence and all-cause mortality based on a large Danish cohort study with 19 years of complete follow-up on responders and nonresponders. Secular trends in mortality based on the whole sample vs responders only illustrated that results based on responders were biased. In a sensitivity analysis, the observed person-years of nonresponders were distributed among six categories of persons with respect to smoking behavior (never-smokers; ex-smokers; noninhaling current smokers; and current smokers of 1-14, 15-24, and > or =25 gm tobacco per day) according to preset assumptions regarding smoking habits. The observed deaths among nonresponders were then distributed on the six smoking categories according to relative risks derived from a Poisson regression analysis among responders. This procedure allowed us to study the effect of adjustment for smoking on the unbiased secular trend in mortality. By applying different assumptions regarding smoking habits among nonresponders, we explored the effect of the assumptions on the adjusted secular trend in mortality. We conclude that secular trends in mortality based on responders in a cohort study are likely to be biased. If complete follow-up on nonresponders is available, this method could prove useful in other cohort studies.

Aged↗
PubMed2004

Comparison of sensitivity analysis methods based on applications to a food safety risk assessment model.

Sensitivity analysis (SA) methods are a valuable tool for identifying critical control points (CCPs), which is one of the important steps in the hazard analysis and CCP approach that is used to ensure safe food. There are many SA methods used across various disciplines. Furthermore, food safety process risk models pose challenges because they often are highly nonlinear, contain thresholds, and have discrete inputs. Therefore, it is useful to compare and evaluate SA methods based upon applications to an example food safety risk model. Ten SA methods were applied to a draft Vibrio parahaemolyticus (Vp) risk assessment model developed by the Food and Drug Administration. The model was modified so that all inputs were independent. Rankings of key inputs from different methods were compared. Inputs such as water temperature, number of oysters per meal, and the distributional assumption for the unrefrigerated time were the most important inputs, whereas time on water, fraction of pathogenic Vp, and the distributional assumption for the weight of oysters were the least important inputs. Most of the methods gave a similar ranking of key inputs even though the methods differed in terms of being graphical, mathematical, or statistical, accounting for individual effects or joint effect of inputs, and being model dependent or model independent. A key recommendation is that methods be further compared by application on different and more complex food safety models. Model independent methods, such as ANOVA, mutual information index, and scatter plots, are expected to be more robust than others evaluated.

Analysis of Variance↗
PubMed2000

Sensitivity analysis of mercury human exposure.

We present a comprehensive analysis of the sensitivity of mercury (Hg) human exposure to environmental variables using a multimedia model of the fate and transport of Hg in the environment. The results of the analysis show that the Hg dose is most sensitive to the lake pH, the burial rate of Hg adsorbed to sediments, and the chemical speciation of Hg emissions to the atmosphere. The lake pH has a strong non-linear effect on the methylation rate and bioaccumulation of Hg in fish. The burial of sediments is a major pathway for removing Hg from the lake cycling. The speciation of Hg emissions is important because Hg(II) is deposited much more rapidly than Hg(0). These results highlight the importance of key variables that should be investigated through well-designed field programs, so that we can minimize the overall uncertainties associated with the modeling of mercury fate and transport.

Confounding Factors, Epidemiologic↗
PubMed2001

A tool model for predicting atmospheric chemical kinetics with sensitivity analysis.

A package(a tool model) for program of predicting atmospheric chemical kinetics with sensitivity analysis is presented. The new direct method of calculating the first order sensitivity coefficients using sparse matrix technology to chemical kinetics is included in the tool model, it is only necessary to triangularize the matrix related to the Jacobian matrix of the model equation. The Gear type procedure is used to integrate a model equation and its coupled auxiliary sensitivity coefficient equations. The FORTRAN subroutines of the model equation, the sensitivity coefficient equations, and their Jacobian analytical expressions are generated automatically from a chemical mechanism. The kinetic representation for the model equation and its sensitivity coefficient equations, and their Jacobian matrix is presented. Various FORTRAN subroutines in packages, such as SLODE, modified MA28, Gear package, with which the program runs in conjunction are recommended. The photo-oxidation of dimethyl disulfide is used for illustration.

Air Pollutants↗
PubMed2002

Sensitivity analysis of stabilization pond system design parameters.

Two stabilization pond systems are examined. A sensitivity analysis is undertaken, aimed at investigating the influence of the pond depths on stabilization pond surface area and pond volume for the specific combination of temperature, wastewater characteristics and effluent requirements. The dependencies are presented in a functional form, allowing for the graphical solution of the unit pond volume, area, and hydraulic residence time as a function of the respective pond depths. Based on these graphs, designers can determine the most appropriate depth value for each type of pond that minimizes the required area or volume, or balances excavation versus land acquisition and floor lining costs, taking under consideration the topographic and other local characteristics of the site area.

Costs and Cost Analysis↗
PubMed2006

A semi-stochastic model of the transmission of Escherichia coli O157 in a typical UK dairy herd: dynamics, sensitivity analysis and intervention/prevention strategies.

When modelling the transmission of infection within small populations, it is necessary to consider the possibility of stochastic fade-out of infection. We present a semi-stochastic model for the transmission of a microparasite, in this case Escherichia coli O157, within a multigroup system, namely a typical UK dairy herd. The model includes birth, death, maturation, the dry/lactating cycle and various types of transmission (i.e. direct, pseudovertical (representing direct faecal-oral transmission between dam and calf within the first 48 h) and indirect (via free-living infectious units in the environment)). We present the results of our simulation study alongside data from empirical studies and also compare simulation results with those for the corresponding deterministic model. We then examine the effects of reducing shedding in the food-producing groups on outbreak size and prevalence of infection. A sensitivity analysis of herd prevalence reveals that, for both the deterministic and the semi-stochastic model, the prevalence within the herd is most sensitive to two parameters relating to the weaned group. This supports our previously reported conclusions for the deterministic model, which were based on an analysis of the next-generation matrix. The sensitivity analysis also indicates that herd prevalence is greatly affected by two other parameters relating to the lactating group. We conclude by discussing the possible efficacy of suggested intervention strategies.

Animals↗
PubMed2005

High sensitivity analysis of oxprenolol in urine by capillary electrophoresis with C18 packed on-line preconcentrator.

High sensitivity analysis of oxprenolol in spiked human urine has been performed by capillary zone electrophoresis (CZE) in ammonium formate buffer pH 2.5 using an uncoated capillary with 1cm length C18 on-capillary preconcentrator at the inlet side. The preconcentrator was fabricated in laboratory using the packing method and not encapped C18 5 microm particles as stationary phase material. The packed path was retained into the capillary by sintered stationary phase frits. Before running the CZE analysis, the oxprenolol was eluted from the preconcentrator by injecting a short plug of acetonitrile/water mixtures. With respect to classical CZE, the use of on-line preconcentrator widely increased the method sensitivity allowing the detection of the drug at 0.5 ng/mL (injected concentration). The method showed a linear response in the range of 1-150 ng/mL oxprenolol standard compound. The intra-day repeatability (n = 11) R.S.D. values for migration time, peak area and normalized peak area were 0.72%, 3.96% and 3.66%, respectively, while inter-day repeatability (n = 5 days) R.S.D. values were 2.74%, 9.41% and 9.83%, respectively. The method was successfully applied to the analysis of oxprenolol in extracted urine spiked at 250 pg/mL (oxprenolol LOQ concentration in urine).

Electrophoresis, Capillary↗
PubMed2001

High-sensitivity analysis of cyanide by capillary electrophoresis with fluorescence detection.

A capillary electrophoretic method for a high-sensitivity analysis of cyanide has been developed. Cyanide was derivatized with 2,3-naphthalenedialdehyde and taurine to give a fluorescent product of 1-cyanobenz[f]isoindole. This compound was detected with high sensitivity by fluorescence detection. The detection limit was 0.1 ng/mL, and the calibration curve was linear over the range 0.1-200 ng/mL. The precision of the migration time of within-run assays (n = 6) of 1 ng/mL cyanide standard solution was 0.14%. The precision of the peak area for the same runs was 1.0%. This method was applicable to blood analysis. Detection of the cyanide derivative by UV was also examined.

Blood Chemical Analysis↗