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Survival Endpoints (survival + endpoint)

Distribution by Scientific Domains
Mathematics and Statistics60%

Selected Abstracts

Modeling Longitudinal Data with Nonparametric Multiplicative Random Effects Jointly with Survival Data

BIOMETRICS, Issue 2 2008
Jimin Ding
Summary In clinical studies, longitudinal biomarkers are often used to monitor disease progression and failure time. Joint modeling of longitudinal and survival data has certain advantages and has emerged as an effective way to mutually enhance information. Typically, a parametric longitudinal model is assumed to facilitate the likelihood approach. However, the choice of a proper parametric model turns out to be more elusive than models for standard longitudinal studies in which no survival endpoint occurs. In this article, we propose a nonparametric multiplicative random effects model for the longitudinal process, which has many applications and leads to a flexible yet parsimonious nonparametric random effects model. A proportional hazards model is then used to link the biomarkers and event time. We use B-splines to represent the nonparametric longitudinal process, and select the number of knots and degrees based on a version of the Akaike information criterion (AIC). Unknown model parameters are estimated through maximizing the observed joint likelihood, which is iteratively maximized by the Monte Carlo Expectation Maximization (MCEM) algorithm. Due to the simplicity of the model structure, the proposed approach has good numerical stability and compares well with the competing parametric longitudinal approaches. The new approach is illustrated with primary biliary cirrhosis (PBC) data, aiming to capture nonlinear patterns of serum bilirubin time courses and their relationship with survival time of PBC patients. [source]

Analysis of Survival Data from Case,Control Family Studies

BIOMETRICS, Issue 3 2002
Joanna H. Shih
Summary. In case,control family studies with survival endpoint, age of onset of diseases can be used to assess the familial aggregation of the disease and the relationship between the disease and genetic or environmental risk factors. Because of the retrospective nature of the case-control study, methods for analyzing prospectively collected correlated failure time data do not apply directly. In this article, we propose a semiparametric quasi-partial-likelihood approach to simultaneously estimate the effect of covariates on the age of onset and the association of ages of onset among family members that does not require specification of the baseline marginal distribution. We conducted a simulation study to evaluate the performance of the proposed approach and compare it with the existing semiparametric ones. Simulation results demonstrate that the proposed approach has better performance in terms of consistency and efficiency. We illustrate the methodology using a subset of data from the Washington Ashkenazi Study. [source]

Investigating the Incidence of type i errors for chronic whole effluent toxicity testing using Ceriodaphnia dubia

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2000
Timothy F. Moore
Abstract The risk of Type I error (false positives) is thought to be controlled directly by the selection of a critical p value for conducting statistical analyses. The critical value for whole effluent toxicity (WET) tests is routinely set to 0.05, thereby establishing a 95% confidence level about the statistical inferences. In order to estimate the incidence of Type I errors in chronic WET testing, a method blank-type study was performed. A number of municipal wastewater dischargers contracted 16 laboratories to conduct chronic WET tests using the standard test organism Ceriodaphnia dubia. Unbeknownst to the laboratories, the samples they received from the wastewater dischargers were comprised only of moderately hard water, using the U.S. Environmental Protection Agency's standard dilution water formula. Because there was functionally no difference between the sample water and the laboratory control/dilution water, the test results were expected to be less than or equal to 1 TUc (toxic unit). Of the 16 tests completed by the biomonitoring laboratories, two did not meet control performance criteria. Six of the remaining 14 valid tests (43%) indicated toxicity (TUc > 1) in the sample (i.e., no-observed-effect concentration or IC25 < 100%). This incidence of false positives was six times higher than expected when the critical value was set to 0.05. No plausible causes for this discrepancy were found. Various alternatives for reducing the rate of Type I errors are recommended, including greater reliance on survival endpoints and use of additional test acceptance criteria. [source]

Sample size considerations for Japanese patients in a multi-regional trial based on MHLW guidance

PHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 2 2010
Hui Quan
Abstract Since the publication of the International Conference on Harmonization E5 guideline, new drug approvals in Japan based on the bridging strategy have been increasing. To further streamline and expedite new drug development in Japan, the Ministry of Health, Labour and Welfare, the Japanese regulatory authority, recently issued the ,Basic Principles on Global Clinical Trials' guidance to promote Japan's participation in multi-regional trials. The guidance, in a Q&A format, provides two methods as examples for recommending the number of Japanese patients in a multi-regional trial. Method 1 in the guidance is the focus of this paper. We derive formulas for the sample size calculations for normal, binary and survival endpoints. Computations and simulation results are provided to compare different approaches. Trial examples are used to illustrate the applications of the approaches. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Adjuvant chemotherapy for bladder cancer does not alter cancer-specific survival after cystectomy in a matched case-control study

BJU INTERNATIONAL, Issue 11 2008
Jochen Walz
OBJECTIVE To assess the effect of adjuvant chemotherapy (ACHT; methotrexate, vinblastine, adriamycin and cisplatin, MVAC, or gemcitabine/cisplatin, GC) on the rate of cancer-specific survival and overall survival, as the benefit of ACHT after radical cystectomy (RC) for bladder cancer is controversial. PATIENTS AND METHODS Within a study group of 958 patients treated with RC between 1984 and 2003, we identified 274 (29.0%) with a high risk of progression due to pT3 or pT4 and/or pN1-3 stages. Of these, 129 (46.6%) received ACHT (MVAC in 103, GC in 26). These patients were then matched with the remaining patients who were unexposed to ACHT. Exact matches were made for pT stage, tumour grade, pN stage and lymphovascular invasion. Age (±5 years) and year of surgery (±5 years) were calliper-matched. Matching resulted in 62 patients treated with RC/ACHT and 65 treated with RC alone. Kaplan-Meier, life-table and Cox regression analyses were used to assess cancer-specific and overall survival. RESULTS There was no statistically significant difference in cancer-specific survival probabilities at 5 years after RC between the two groups (relative risk 1.2; P = 0.5). There was also no difference in overall survival at 5 years (1.1; P = 0.7). In multivariable analyses the delivery of adjuvant chemotherapy was not an independent predictor for survival endpoints (P = 0.3 for cancer-specific and 0.3 for overall survival). CONCLUSIONS This matched case-control analysis showed that either MVAC or GC chemotherapy had no effect on cancer-specific or overall survival after RC in high-risk patients. Further randomized long-term studies are necessary to confirm these results. [source]