Regression trees for multivalued numerical response variables

2017 ◽  
Vol 69 ◽  
pp. 21-28 ◽  
Author(s):  
Antonio D’Ambrosio ◽  
Massimo Aria ◽  
Carmela Iorio ◽  
Roberta Siciliano
Author(s):  
Nisha Patel ◽  
Hitesh A Patel

In this study, we sought to improve the dissolution characteristics of a poorly water-soluble BCS class IV drug canaglifozin, by preparing nanosuspension using media milling method. A Plackett–Burman screening design was employed to screen the significant formulation and process variables. A total of 12 experiment were generated by design expert trial version 12 for screening 5 independent variables namely the amount of stabilizer in mg (X1), stirring time in hr (X2), amt of Zirconium oxide beads in gm (X3), amount of drug in mg (X4) and stirring speed in rpm (X5) while mean particle size in nm (Y1) and drug release in 10 min. were selected as the response variables. All the regression models yielded a good fit with high determination coefficient and F value. The Pareto chart depicted that all the independent variables except the amount of canaglifozin had a significant effect (p<0.001) on the response variables. The mathematical model for mean particle size generated from the regression analysis was given by mean particle size = +636.48889 -1.28267 amt of stabilizer(X1) -4.20417 stirring time (X2) -7.58333 amt of ZrO2 beads(X3) -0.105556 amt of drug(X4) -0.245167 stirring speed(X5) (R2=0.9484, F ratio=22.07, p<0.001). Prepared canaglifozin nanosuspension exemplified a significant improvement (p<0.05) in the release as compared to pure canaglifozin and marketed tablet with the optimum formulation releasing almost 80% drug within first 10min. Optimized nanosuspension showed spherical shape with surface oriented stabilizer molecules and a mean particle diameter of 120.5 nm. There was no change in crystalline nature after formulation and it was found to be chemically stable with high drug content.


2020 ◽  
Vol 17 (6) ◽  
pp. 523-539
Author(s):  
Jalpa Patel ◽  
Dhaval Mori

Background: Developing a new excipient and obtaining its market approval is an expensive, time-consuming and complex process. Compared to that, the co-processing of already approved excipients has emerged as a more attractive option for bringing better characteristic excipients to the market. The application of the Design of Experiments (DoE) approach for developing co-processed excipient can make the entire process cost-effective and rapid. Objective: The aim of the present investigation was to demonstrate the applicability of the DoE approach, especially 32 full factorial design, to develop a multi-functional co-processed excipient for the direct compression of model drug - cefixime trihydrate using spray drying technique. Methods: The preliminary studies proved the significant effect of atomization pressure (X1) and polymer ratio (microcrystalline cellulose: mannitol - X2) on critical product characteristics, so they were selected as independent variables. The angle of repose, Carr’s index, Hausner’s ratio, tensile strength and Kuno’s constant were selected as response variables. Result: The statistical analysis proved a significant effect of both independent variables on all response variables with a significant p-value < 0.05. The desirability function available in Design Expert 11® software was used to prepare and select the optimized batch. The prepared co-processed excipient had better compressibility than individual excipients and their physical mixture and was able to accommodate more than 40 percent drug without compromising the flow property and compressibility. Conclusion: The present investigation successfully proved the applicability of 32 full factorial design as an effective tool for optimizing the spray drying process to prepare a multi-functional co-processed excipient.


Author(s):  
Jiemin Xie ◽  
Jun Zhang ◽  
Xuan Xie ◽  
Zhiwei Bi ◽  
Zhuoheng Li

2021 ◽  
Vol 9 (7) ◽  
pp. 232596712110152
Author(s):  
Lucas G. Teske ◽  
Edward C. Beck ◽  
Garrett S. Bullock ◽  
Kristen F. Nicholson ◽  
Brian R. Waterman

Background: Although lower extremity biomechanics has been correlated with traditional metrics among baseball players, its association with advanced statistical metrics has not been evaluated. Purpose: To establish normative biomechanical parameters during the countermovement jump (CMJ) among Major League Baseball (MLB) players and evaluate the relationship between CMJ-developed algorithms and advanced statistical metrics. Study Design: Cohort study; Level of evidence, 3. Methods: MLB players in 2 professional organizations performed the CMJ at the beginning of each baseball season from 2013 to 2017. We collected ground-reaction force data including the eccentric rate of force development (“load”), concentric vertical force (“explode”), and concentric vertical impulse (“drive”) as well as the Sparta Score. The advanced statistical metrics from each baseball season (eg, fielding independent pitching [FIP], weighted stolen base runs [wSB], and weighted on-base average) were also gathered for the study participants. The minimal detectable change (MDC) was calculated for each CMJ variable to establish normative parameters. Pearson coefficient analysis and regression trees were used to evaluate associations between CMJ data and advanced statistical metrics for the players. Results: A total of 151 pitchers and 138 batters were included in the final analysis. The MDC for “load,” “explode,” “drive,” and the Sparta Score was 10.3, 8.1, 8.7, and 4.6, respectively, and all demonstrated good reliability (intraclass correlation coefficient > 0.75). There was a weak but statistically significant correlation between the Sparta Score and wSB ( r = 0.23; P = .007); however, there were no significant correlations with any other advanced metrics. Regression trees demonstrated superior FIP with higher Sparta Scores in older pitchers compared with younger pitchers. Conclusion: There was a positive but weak correlation between the Sparta Score and base-stealing performance among professional baseball players. Additionally, older pitchers with a higher Sparta Score had statistically superior FIP compared with younger pitchers with a similar Sparta Score after adjusting for age.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1252.2-1253
Author(s):  
R. Garofoli ◽  
M. Resche-Rigon ◽  
M. Dougados ◽  
D. Van der Heijde ◽  
C. Roux ◽  
...  

Background:Axial spondyloarthritis (axSpA) is a chronic rheumatic disease that encompasses various clinical presentations: inflammatory chronic back pain, peripheral manifestations and extra-articular manifestations. The current nomenclature divides axSpA in radiographic (in the presence of radiographic sacroiliitis) and non-radiographic (in the absence of radiographic sacroiliitis, with or without MRI sacroiliitis. Given that the functional burden of the disease appears to be greater in patients with radiographic forms, it seems crucial to be able to predict which patients will be more likely to develop structural damage over time. Predictive factors for radiographic progression in axSpA have been identified through use of traditional statistical models like logistic regression. However, these models present some limitations. In order to overcome these limitations and to improve the predictive performance, machine learning (ML) methods have been developed.Objectives:To compare ML models to traditional models to predict radiographic progression in patients with early axSpA.Methods:Study design: prospective French multicentric cohort study (DESIR cohort) with 5years of follow-up. Patients: all patients included in the cohort, i.e. 708 patients with inflammatory back pain for >3 months but <3 years, highly suggestive of axSpA. Data on the first 5 years of follow-up was used. Statistical analyses: radiographic progression was defined as progression either at the spine (increase of at least 1 point per 2 years of mSASSS scores) or at the sacroiliac joint (worsening of at least one grade of the mNY score between 2 visits). Traditional modelling: we first performed a bivariate analysis between our outcome (radiographic progression) and explanatory variables at baseline to select the variables to be included in our models and then built a logistic regression model (M1). Variable selection for traditional models was performed with 2 different methods: stepwise selection based on Akaike Information Criterion (stepAIC) method (M2), and the Least Absolute Shrinkage and Selection Operator (LASSO) method (M3). We also performed sensitivity analysis on all patients with manual backward method (M4) after multiple imputation of missing data. Machine learning modelling: using the “SuperLearner” package on R, we modelled radiographic progression with stepAIC, LASSO, random forest, Discrete Bayesian Additive Regression Trees Samplers (DBARTS), Generalized Additive Models (GAM), multivariate adaptive polynomial spline regression (polymars), Recursive Partitioning And Regression Trees (RPART) and Super Learner. Finally, the accuracy of traditional and ML models was compared based on their 10-foldcross-validated AUC (cv-AUC).Results:10-fold cv-AUC for traditional models were 0.79 and 0.78 for M2 and M3, respectively. The 3 best models in the ML algorithm were the GAM, the DBARTS and the Super Learner models, with 10-fold cv-AUC of: 0.77, 0.76 and 0.74, respectively (Table 1).Table 1.Comparison of 10-fold cross-validated AUC between best traditional and machine learning models.Best modelsCross-validated AUCTraditional models M2 (step AIC method)0.79 M3 (LASSO method)0.78Machine learning approach SL Discrete Bayesian Additive Regression Trees Samplers (DBARTS)0.76 SL Generalized Additive Models (GAM)0.77 Super Learner0.74AUC: Area Under the Curve; AIC: Akaike Information Criterion; LASSO: Least Absolute Shrinkage and Selection Operator; SL: SuperLearner. N = 295.Conclusion:Traditional models predicted better radiographic progression than ML models in this early axSpA population. Further ML algorithms image-based or with other artificial intelligence methods (e.g. deep learning) might perform better than traditional models in this setting.Acknowledgments:Thanks to the French National Society of Rheumatology and the DESIR cohort.Disclosure of Interests:Romain Garofoli: None declared, Matthieu resche-rigon: None declared, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Christian Roux: None declared, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB


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