Aflibercept versus placebo in combination with FOLFIRI in previously treated metastatic colorectal cancer (mCRC): Mean overall survival (OS) estimation from a phase III trial (VELOUR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3602-3602 ◽  
Author(s):  
Florence Joulain ◽  
Eric Van Cutsem ◽  
Sheikh Usman Iqbal ◽  
Martin Hoyle ◽  
Carmen Joseph Allegra
Keyword(s):  
Decision Support ◽  
Median Survival ◽  
Survival Data ◽  
Goodness Of Fit ◽  
Graphical Method ◽  
Survival Function ◽  
Information Criteria ◽  
Phase Iii ◽  
Economic Decision ◽  
Previously Treated

3602 Background: VELOUR evaluated the efficacy and safety of the novel fusion protein aflibercept (VEGF Trap) in combination with FOLFIRI in mCRC patients previously treated with oxaliplatin. Median OS showed significant improvement with 12.06 months in placebo arm vs 13.50 months in aflibercept arm (p=0.0032; HR=0.82 [95.34% CI: 0.71 to 0.94]) [Van Cutsem, 2011]. Since survival data in oncology are usually right skewed, median survival is preferred for regulatory purposes. However, mean survival estimation can render a more meaningful estimate for long term benefit of interventions, and be effectively applied to clinical and economic decision support. Estimating mean OS also allows payers to derive an estimation of total costs and outcomes in the population. The purpose of this study was to estimate the mean OS for VELOUR trial. Methods: During the trial follow-up period, mean OS is not observable and can be estimated by extrapolating the trial Kaplan-Meier curve using a survival function. Several standard parametric distributions were tested: exponential, weibull, lognormal, loglogistic and gompertz. Akaike’s Information Criteria (AIC), Bayesian Information Criteria (BIC) and graphical method were used to evaluate the goodness of fit of the distributions. Models were run by treatment arm separately or combining the two arms and using treatment as covariate to control for variation. Results: Using AIC/BIC and graphical method, loglogistic function best fit the VELOUR data both with and without treatment as covariate. Weibull distribution is used for sensitivity analysis. Conclusions: Using loglogistic function, mean OS benefit for aflibercept in combination with FOLFIRI is at least 2.9 months (versus 1.4 months difference in median survival). The results have important implications for clinical and economic decision support. Study NCT00561470 was funded by sanofi, in partnership with Regeneron. [Table: see text]

Cabazitaxel or mitoxantrone with prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Estimating mean overall survival (OS) for health economic analyses from a phase III trial (TROPIC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
S. Oudard ◽  
F. Joulain ◽  
A. De Geer ◽  
A. O. Sartor
Keyword(s):  
Goodness Of Fit ◽  
Graphical Method ◽  
Survival Function ◽  
Information Criteria ◽  
Phase Iii ◽  
Point Estimate ◽  
Weibull Function ◽  
Term Survival ◽  
Kaplan Meier ◽  
Previously Treated

128^ Background: TROPIC evaluated the efficacy and safety of the novel taxane cabazitaxel in men with mCRPC previously treated with docetaxel. Median OS was significantly improved, as previously reported (12.7 months in mitoxantrone arm vs 15.1 months in cabazitaxel arm, HR=0.72 [0.61 – 0.84], p<0.0001- updated OS results). Median OS is the most useful descriptive statistic for physicians and patients as it reflects a point estimate in time by which 50% patients may survive regardless of disease status or progression. It avoids assumptions on long-term survival beyond the follow-up period of the clinical trial. Payers however are interested in making a coverage and reimbursement decisions based on the overall therapeutic benefit relative to its risk, and the expected impact on healthcare expenditures. Analyses such as cost-effectiveness analysis therefore require the estimation of mean OS. Methods: Mean OS is only observable when the last patient has died. Its estimation can be derived via an extrapolation of the trial Kaplan-Meier curve using a survival function. Several parametric distributions (exponential, weibull, lognormal, loglogistic and Gompertz) were tested. The parametric distribution that best fitted the trial Kaplan-Meier curves was selected using the Akaike's Information criteria (AIC), the Bayesian Information Criteria (BIC) and graphical method to evaluate the goodness of fit of the distributions. Mean OS from the best fitted model was generated to support payer decision making. Results: Using AIC/BIC and graphical method, the Weibull survival function, S(t)=exp(-l ts) where l is a scale parameter and s a shape parameter, was selected as the distribution that best fitted the TROPIC data. Results of the estimated mean survival assuming a Weibull function are described in the table. Conclusions: Assuming a Weibull distribution, mean OS is estimated at 14.5 months in mitoxantrone arm vs 18.5 months in cabazitaxel arm, leading to 4 months OS difference in favour of cabazitaxel. [Table: see text] [Table: see text]

Survival of patients (pts) with metastatic melanoma treated with the anti-CTLA4 monoclonal antibody (mAb) CP-675,206 in a phase I/II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8524-8524 ◽  
Author(s):  
J. Gomez-Navarro ◽  
S. Antonia ◽  
J. Sosman ◽  
J. M. Kirkwood ◽  
B. Redman ◽  
...  
Keyword(s):  
Phase I ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Phase Ii ◽  
Survival Data ◽  
Phase I Study ◽  
Objective Response ◽  
Phase Iii ◽  
Open Label ◽  
Expansion Cohort

8524 Background: The fully human anti-CTLA4 mAb CP-675,206 has demonstrated clinical activity in pts with metastatic melanoma. Prolonged survival was observed in a prior single-dose phase I study, even in pts who did not achieve objective tumor responses. Methods: A multidose phase I/II trial was conducted in pts (N = 119) with histologically confirmed stage IIIc (unresectable) or stage IV recurrent metastatic melanoma and ECOG PS = 1. The study consisted of a phase I, open-label, multidose study (3, 6, and 10 mg/kg) and a phase I expansion cohort for HLA-A2.1+ pts (10 mg/kg monthly [Q1M]), followed by a phase II open-label study of 2 dosing regimens: 10 mg/kg Q1M and 15 mg/kg every 3 months (Q3M). The primary endpoint was safety in phase I, immune monitoring in the expansion cohort, and response in phase II. Survival was analyzed as a secondary endpoint. Results: In the phase I study, Kaplan-Meier estimates of median overall survival were 17.6 months for all dose groups combined (n = 28). In the phase II study, median survival was 10.3 months in the 10 mg/kg arm and 11.0 months in the 15 mg/kg arm. Survival outcomes were favorable, compared with historical median survival of 7 months, independent of whether pts achieved an objective response. Updated survival data will be presented. Conclusions: Patients participating in a multiple dose study of CP-675,206 showed a survival time that was greater than expected on historic controls. These observations support the endpoints of an ongoing randomized phase III study in melanoma to further evaluate survival in the frontline setting. [Table: see text] [Table: see text]

scholarly journals The Effect of Exclusive Breastfeeding on Child Survival Using Modified Kaplan Meier Model (MKMM)

2019 ◽  
pp. 1-10
Author(s):  
Moses Longji Dashal ◽  
Kazeem Eyitayo Lasisi ◽  
Kaneng Eileen Longji
Keyword(s):  
Exclusive Breastfeeding ◽  
Survival Data ◽  
Survival Probability ◽  
Survival Function ◽  
Child Survival ◽  
Food Supplement ◽  
Information Criteria ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Milk Substitute

Background: In Survival analysis, Kaplan-Meier estimator serves as a tool for measuring the frequency or the number of patients surviving medical treatment. Kaplan Meier estimates of survival data have become a better way of analyzing data in cohort study. Kaplan- Meier (K-M) is a non-parametric estimates of survival function that is commonly used to describe survivorship of a study population and to compare two study populations. Aims: This research study is aimed at reducing the morbidity and mortality rate of children less than 6 months. Methodology: 58,609 children less than six months were Exclusive Breastfed from the database. The analysis is done using both K-M and the modified K-M model to examine the effects of Exclusive Breastfeeding. The AIC and BIC was also used as the information criteria. Results: Our results revealed that the K-M model 0.998566822 as the estimated survival probability of children under the ages of six months. Also showing, Exclusively Breastfed children stand the chance of 99% survival. The modified K-M model also revealed 6.98276443909739 as the estimated survival probability, due to initiation of milk substitute and food supplement into the breastfeeding pattern. Showing about 70% chances of survival. Implying about 30% of the existence in one disease or the other or the risk of dying before the age of 5 years. From the information criteria, the AIC (2.3119452169420) and BIC (7.8478797677756) in the Modified K-M are both lower compared to Existing Kaplan Meier (4.0012457354876) and (9.5371847322969) respectively. Modified K-M stand as the best model in knowing the types/amount of food to be added to breastfeeding pattern. Conclusion: So far, the Modified Kaplan Meier Model has been verified and the findings agree that the life expectation will be improved by 99% if children are fed exclusively with breast milk while the life span is been reduced that can lead to death by 30% if the children have a mix feeding which agrees with why Exclusive Breastfeeding should be done.

Open-label study of pemetrexed alone for chemonaive patients and pre-treated patients with malignant pleural mesothelioma: Outcomes of the International Expanded Access Program (EAP)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7709-7709
Author(s):  
P. Taylor ◽  
J. von Pawel ◽  
B. Castagneto ◽  
G. Dark ◽  
M. Marangolo ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Survival Data ◽  
Single Agent ◽  
Safety Data ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Open Label ◽  
Pretreated Group

7709 Background: In a previous phase II study of chemonaive malignant pleural mesothelioma (MPM) patients (pts), single-agent pemetrexed (P) resulted in a 14.1% response rate (RR) and median survival of 10.7 mos (95% CI 7.7–14.5) (Scagliotti 2003). Likewise, the P arm in a phase III study of pre-treated MPM pts yielded an 18.7% RR (40.7% with stable disease, SD) and median survival of 8.4 mos (95% CI 6.2–10.5) (Jassem 2006). The EAP provided 3311 MPM pts with access to P alone, P plus cisplatin, or P plus carboplatin in 13 countries. In this abstract we report on the safety and efficacy data of those MPM pts treated with P alone. Methods: Eligible pts had histologic or cytologic diagnosis of MPM and were either chemonaïve or previously treated with =1 line(s) of chemotherapy. Pts pre-treated with P were allowed if they had experienced clinical benefit from the prior P. Treatment consisted of P (500 mg/m2) once (day 1) every 21 days with standard pre-medication of vitamin B12, folic acid, and dexamethasone. Investigator-determined response (RR) and survival data (with censoring) were recorded at the end of study participation. Myelosuppression data (CTC) were also collected. Results: 812 MPM pts (319 chemonaïve; 493 pre-treated) received =1 dose of P and were evaluated for safety, and 643 pts (247 chemonaïve; 396 pre-treated) were evaluated for efficacy (RR and survival). In chemonaïve pts with MPM, the median age was 69 yrs (range: 39–87 yrs), 78.1% were male, and 71.6% had a KPS ≥80 (of the 93% who had PS evaluated). In pre-treated pts with MPM, the median age was 63 yrs (range: 31–85 yrs), 75.9% were male, and 74.5% had a KPS ≥80 (of the 95% who had PS evaluated). Both groups received a median of 4 cycles (chemonaive group range 1–18; pretreated group range 1–23). See the table for efficacy and safety data. Conclusions: Results of the EAP confirm earlier phase II and phase III studies. No significant financial relationships to disclose. [Table: see text]

Ipilimumab in metastatic malignant melanoma: The Irish experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19059-e19059
Author(s):  
Paul P. Donnellan ◽  
Richard Bambury ◽  
Jodie E Battley ◽  
Derek Gerard Power ◽  
Kenneth John O'Byrne ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Adverse Events ◽  
Survival Data ◽  
Surrogate Marker ◽  
Metastatic Malignant Melanoma ◽  
Median Number ◽  
Phase Iii ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Grade 3

e19059 Background: Ipilimumab (Ipi) is a potent anti CLA-4 immunotherapy recently shown to improve overall survival (OS) in a phase III study in patients (pts) with previously-treated, unresectable or metastatic malignant melanoma. Ipilimumab (3 mg/kg) has been available on compassionate grounds to pts in Ireland since June 2010. Methods: In this retrospective observational study we examine the Irish experience with ipilimumab specifically regarding patient-factors, treatment toxicity, and outcomes including response rate and survival. Results: Between June 2010 and December 2011, a total of 93 patients received ipilimumab. Data available for analyses was conducted in 46patients. Median age of patients was 56 yrs (ranging 28 – 84). M1c disease was identified in 40 patients (83.3%). Median number of prior lines of chemotherapy is 1 (ranging from 1-4). 22 (47.8%) patients received all four planned induction doses of ipilimumab. All patients received full doses of treatment and on schedule. There are no grade 4 toxicities reported and 13% (n= 6) had grade 3 adverse events. This included renal autoimmune toxicity (n=3), diarrhoea (n=1) elevated AST/ALT (n=1), ocular toxicity (n=1) and skin (n=1). Grade 3 adverse events occurred in 3 patients who received all 4 cycles of Ipilimumab. No intestinal perforations or hypophysitis were noted. There were no drug-related deaths. From available survival follow-up data there are 22 reported deaths. Due to paucity of the data, surrogate marker for response of treatment was expressed as absence of disease progression at the time of assessment. Among the 11 (23.9%) patients who responded to treatment, 45.5% of these patients received 4 cycles of ipilimumab. Conclusions: Ipilimumab was well tolerated with a manageable side effect profile. Response rates to ipilimumab in metastatic melanoma in an Irish population are in keeping with internationally reported figures. Comprehensive survival data will be reported as well as correlation of response with hematologic and biochemical blood tests.

scholarly journals Facilitating Genetics Aware Clinical Decision Support: Putting the eMERGE Infrastructure into Practice

ACI Open ◽  
2021 ◽  
Vol 05 (02) ◽  
pp. e54-e58
Author(s):  
Casey Overby Taylor ◽  
Luke V. Rasmussen ◽  
Laura J. Rasmussen-Torvik ◽  
Cynthia A. Prows ◽  
David A. Dorr ◽  
...  
Keyword(s):  
Decision Support ◽  
Electronic Medical Records ◽  
Clinical Decision Support ◽  
Medical Records ◽  
Case Reports ◽  
Clinical Decision ◽  
Phase Iii ◽  
Health Record ◽  
It Infrastructure ◽  
Emerge Network

AbstractThis editorial provides context for a series of published case reports in ACI Open by summarizing activities and outputs of joint electronic health record integration and pharmacogenomics workgroups in the NIH-funded electronic Medical Records and Genomics (eMERGE) Network. A case report is a useful tool to describe the range of capabilities that an IT infrastructure or a particular technology must support. The activities we describe have informed infrastructure requirements used during eMERGE phase III, provided a venue to share experiences and ask questions among other eMERGE sites, summarized potential hazards that might be encountered for specific clinical decision support (CDS) implementation scenarios, and provided a simple framework that captured progress toward implementing CDS at eMERGE sites in a consistent format.

Empirical comparison of skewed t-copula models for insurance and financial data

2020 ◽  
Vol 15 (4) ◽  
pp. 351-361
Author(s):  
Liwei Huang ◽  
Arkady Shemyakin
Keyword(s):  
Bayesian Estimation ◽  
Goodness Of Fit ◽  
Model Performance ◽  
Information Criteria ◽  
Stock Index ◽  
Likelihood Method ◽  
Special Importance ◽  
Copula Model ◽  
Technical Problems ◽  
T Copula

Skewed t-copulas recently became popular as a modeling tool of non-linear dependence in statistics. In this paper we consider three different versions of skewed t-copulas introduced by Demarta and McNeill; Smith, Gan and Kohn; and Azzalini and Capitanio. Each of these versions represents a generalization of the symmetric t-copula model, allowing for a different treatment of lower and upper tails. Each of them has certain advantages in mathematical construction, inferential tools and interpretability. Our objective is to apply models based on different types of skewed t-copulas to the same financial and insurance applications. We consider comovements of stock index returns and times-to-failure of related vehicle parts under the warranty period. In both cases the treatment of both lower and upper tails of the joint distributions is of a special importance. Skewed t-copula model performance is compared to the benchmark cases of Gaussian and symmetric Student t-copulas. Instruments of comparison include information criteria, goodness-of-fit and tail dependence. A special attention is paid to methods of estimation of copula parameters. Some technical problems with the implementation of maximum likelihood method and the method of moments suggest the use of Bayesian estimation. We discuss the accuracy and computational efficiency of Bayesian estimation versus MLE. Metropolis-Hastings algorithm with block updates was suggested to deal with the problem of intractability of conditionals.

scholarly journals Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1284
Author(s):  
Nicolas Delanoy ◽  
Debbie Robbrecht ◽  
Mario Eisenberger ◽  
Oliver Sartor ◽  
Ronald de Wit ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Post Hoc Analysis ◽  
Psa Response ◽  
Phase Iii Study ◽  
Psa Progression ◽  
Previously Treated ◽  
Post Hoc

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

scholarly journals Container Throughput Forecasting Using Dynamic Factor Analysis and ARIMAX Model

2017 ◽  
Vol 29 (5) ◽  
pp. 529-542 ◽  
Author(s):  
Marko Intihar ◽  
Tomaž Kramberger ◽  
Dejan Dragan
Keyword(s):  
Factor Analysis ◽  
Goodness Of Fit ◽  
Moving Average ◽  
Real Data ◽  
Information Criteria ◽  
Dynamic Factor Analysis ◽  
Forecasting Model ◽  
Dynamic Factor ◽  
Macroeconomic Indicators ◽  
The Impact

The paper examines the impact of integration of macroeconomic indicators on the accuracy of container throughput time series forecasting model. For this purpose, a Dynamic factor analysis and AutoRegressive Integrated Moving-Average model with eXogenous inputs (ARIMAX) are used. Both methodologies are integrated into a novel four-stage heuristic procedure. Firstly, dynamic factors are extracted from external macroeconomic indicators influencing the observed throughput. Secondly, the family of ARIMAX models of different orders is generated based on the derived factors. In the third stage, the diagnostic and goodness-of-fit testing is applied, which includes statistical criteria such as fit performance, information criteria, and parsimony. Finally, the best model is heuristically selected and tested on the real data of the Port of Koper. The results show that by applying macroeconomic indicators into the forecasting model, more accurate future throughput forecasts can be achieved. The model is also used to produce future forecasts for the next four years indicating a more oscillatory behaviour in (2018-2020). Hence, care must be taken concerning any bigger investment decisions initiated from the management side. It is believed that the proposed model might be a useful reinforcement of the existing forecasting module in the observed port.

Sign in / Sign up

Export Citation Format

Share Document