showing 33 related works from this author
Sample size planning of two-arm superiority and noninferiority survival studies with discrete follow-up
2016
In clinical trials using lifetime as primary outcome variable, it is more the rule than the exception that even for patients who are failing in the course of the study, survival time does not become known exactly since follow-up takes place according to a restricted schedule with fixed, possibly long intervals between successive visits. In practice, the discreteness of the data obtained under such circumstances is plainly ignored both in data analysis and in sample size planning of survival time studies. As a framework for analyzing the impact of making no difference between continuous and discrete recording of failure times, we use a scenario in which the partially observed times are assig…
Testing for goodness rather than lack of fit of an X–chromosomal SNP to the Hardy-Weinberg model
2019
The problem of checking the genotype distribution obtained for some diallelic marker for compatibility with the Hardy-Weinberg equilibrium (HWE) condition arises also for loci on the X chromosome. The possible genotypes depend on the sex of the individual in this case: for females, the genotype distribution is trinomial, as in the case of an autosomal locus, whereas a binomial proportion is observed for males. Like in genetic association studies with autosomal SNPs, interest is typically in establishing approximate compatibility of the observed genotype frequencies with HWE. This requires to replace traditional methods tailored for detecting lack of fit to the model with an equivalence test…
Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer.
2005
OBJECTIVES To report the long-term follow-up of patients with locally advanced bladder cancer treated with either adjuvant combined chemotherapy with methotrexate, vinblastine, doxorubicin/epirubicin, and cisplatin (MVAC/MVEC) or no additional treatment after radical cystectomy, to examine various survival endpoints and factors associated with long-term survival. PATIENTS AND METHODS Between May 1987 and December 1990, 49 patients undergoing radical cystectomy for locally advanced bladder cancer were randomized to observation only or adjuvant systemic chemotherapy with three cycles of MVAC/MVEC (methotrexate 30 mg/m2 on day 1, 15 and 22; vinblastine 3 mg/m2 on day 2, 15 and 22; doxorubicin …
Sonographic size of uterus and ovaries in pre- and postmenopausal women
1996
Uterine and ovarian size were measured in 765 pre- and postmenopausal women by transvaginal ultrasound. Of these, 263 (premenopausal, n = 155; postmenopausal, n = 108) were found to have neither uterine nor ovarian pathological findings. According to parity, premenopausal women were separated into three groups: nullipara, primipara and multipara. Postmenopausal women were separated into two groups according to years since menopause: 5 years since menopause. In the premenopausal group, a parity-related enlargement in uterine size was observed between nulliparous and parous women. After the menopause, a significant reduction in uterine size and in the corpus-cervix ratio was observed. The red…
A Log-Rank Test for Equivalence of Two Survivor Functions
1993
We consider a hypothesis testing problem in which the alternative states that the vertical distance between the underlying survivor functions nowhere exceeds some prespecified bound delta0. Under the assumption of proportional hazards, this hypothesis is shown to be (logically) equivalent to the statement [beta[log(1 + epsilon), where beta denotes the regression coefficient associated with the treatment group indicator, and epsilon is a simple strictly increasing function of delta. The testing procedure proposed consists of carrying out in terms of beta (i.e., the standard Cox likelihood estimator of beta) the uniformly most powerful level alpha test for a suitable interval hypothesis about…
Vorschläge zur Reformulierung der statistischen Definition von Bioäquivalenz
1990
Gegen das herkommliche, nur die Erwartungswerte berucksichtigende Bioaquivalenzkriterium last sich der Einwand mangelnder Relevanz fur den Emzelfall geltend machen. Beide zur Behebung dieses Mangels vorgeschlagenen Ansatze betrachten als primar interessierende Grose die Wahrscheinlichkeit eines Ereignisses, das die individuelle Reaktion gegenuber der Test (T) — und der Referenzformulierung (R) eines gegebenen Wirkstoffs beschreibt. Ansatz (I) fuhrt auf einen einfachen Binomialtest mit der Anzahl von Probanden, bei denen der individuell beobachtete Bioverfugbarkeitsquotient im Sinne des 80–120%-Kriteriums akzeptabel ist. Der Test ist gleichmasg bester unter allen verteilungsfreien Tests zur …
No association of alcohol dependence with a NMDA-receptor 2B gene variant
2003
On the use of asymptotic expansion in computing the null distribution of page's L-statistic
1989
Suppose that each out of n randomized complete blocks is obtained by observing a jointly continuous random variable taking values in Rk. Page's L-statistic is given then as a sum of i.i.d. lattice variables with finite moments of any order. Applying a well-known theorem on asymptotic expansions for the distribution function of such a sum yields higher order approximations to the significance probability of any observed value of L. The formula obtained by discarding terms smaller than o(n –1) is still very simple to use. Yet, due to it's strong analytical basis, it can be expected to provide substantial improvement on the traditional normal approximation. The results of extensive numerical i…
Planning and Analysis of Trials Using a Stepped Wedge Design: Part 26 of a Series on Evaluation of Scientific Publications
2019
Background The stepped-wedge design (SWD) of clinical trials has become very popular in recent years, particularly in health services research. Typically, study participants are randomly allotted in clusters to the different treatment options. Methods The basic principles of the stepped wedge design and related statistical techniques are described here on the basis of pertinent publications retrieved by a selective search in PubMed and in the CIS statistical literature database. Results In a typical SWD trial, the intervention is begun at a time point that varies from cluster to cluster. Until this time point is reached, all participants in the cluster belong to the control arm of the trial…
Knowledge about glaucoma in the unselected population: a German survey.
2002
Purpose To determine the general population's knowledge about glaucoma. Materials and methods A representative survey of the German population was conducted in which 2,742 men and women were interviewed face to face. The sample was matched with the German population for age, sex, education, income, and other factors. Questions were asked concerning the nature, occurrence, possible risk factors, and course of glaucoma. Results Fifty-one percent of the population had an active knowledge of the term "glaucoma" and 75% had a passive knowledge of the term. Of those interviewees with a passive knowledge, glaucoma was thought to be associated with raised intraocular pressure (IOP) by 28% and loss …
Basing the Analysis of Comparative Bioavailability Trials on an Individualized Statistical Definition of Equivalence
1993
The conventional definition of bioequivalence in terms of population means only, is criticized for lacking relevance to the individual subject. Both approaches to bioequivalence assessment proposed here for avoiding this shortcoming, focus on the probability of an event induced by the response of a randomly selected subject to two formulations of a given active agent. The first approach leads to converting the basic idea underlying the well-known 75-rule into an exact statistical procedure. The second approach is of a parametric nature. It reduces bioequivalence assessment to testing against the alternative hypothesis that the standardized expected value of a Gaussian distribution is contai…
Equivalence Testing With Particle Size Distribution Data: Methods and Applications in the Development of Inhalative Drugs
2017
ABSTRACTKey criteria of the quality of inhalative drugs are assessed in experiments generating so-called particle size distributions as data. Many experiments of that kind are carried out to demonstrate that necessary modifications to whatever part of the manufacturing process do not substantially change basic characteristics of an inhalable drug product. The equivalence testing procedures we derive for that purpose rely on different models accommodating the specific structure of such data and on different ways of specifying the region of nonrelevant differences. For each hypotheses formulation, three different tests are derived (two parametric and one asymptotically distribution-free proce…
Anforderungen an das Meßskalen-Niveau von Kovariablen im Proportional-Hazards-Modell
1992
Die Frage nach dem erforderlichen Messkalen-Niveau der Kovariablen in einem Proportional-Hazards-Modell (PHM) wird in der Literatur uber die Anwendung der Methodologie der Cox-Regression bei der Auswertung klinischer Studien kaum je in einem technisch prazisen Sinne gestellt. Nach den kurzlich publizierten Empfehlungen der Arbeitsgruppe „Statistische Methoden in der Medizin“ der DR der Biometrischen Gesellschaft und der GMDS zu schliesen [ULM et al. (1989)], scheint dennoch mittlerweile ein relativ breiter Konsens daruber zu bestehen, das explanatorische Variablen mit ordinaler Struktur bei der Handhabung des PHM als Auswertungsinstrument fur klinische Studien problematisch sein konnen. An …
Radical cystectomy with or without adjuvant polychemotherapy for non-organ-confined transitional cell carcinoma of the urinary bladder: prognostic im…
1996
To analyze the effectiveness of adjuvant polychemotherapy after radical cystectomy for non-organ-confined transitional cell bladder cancer (Stages pT3b, pT4a, and/or pN1 or pN2).Of 166 consecutive patients undergoing cystectomy at two institutions from 1987 to 1993, 80 received adjuvant polychemotherapy with methotrexate, vinblastine, and cisplatin plus doxorubicin (MVAC) or epirubicin (MVEC), whereas 86 had cystectomy only. The patients were evaluated for relapse-free survival and length of progression-free interval on the basis of follow-up data obtained in 1995 and 1996.Kaplan-Meier analysis revealed a significantly higher progression-free rate for patients after adjuvant chemotherapy (P…
DNA image cytometry in stomach carcinoma. Its relation to histomorphologic parameters and its influence on prognosis
1992
BACKGROUND The influence of DNA content on the prognosis in stomach cancer is controversial. METHOD After curative resection of stomach carcinomas (adenocarcinomas [n = 58]; signet ring cell carcinomas [n = 24]; undifferentiated carcinomas [n = 21]), the influence of the DNA content and histomorphologic parameters on the prognosis was examined. RESULTS In the multivariate regression analysis, the prognosis depended on the lymph node status (P = 0.0009), pT stage (P = 0.02), tumor localization (P = 0.03), and histologic type (P = 0.05). The prognosis was independent of the DNA content. Furthermore, the degree of differentiation, operative procedure, safety distance, size of the tumor, and se…
Prognostic value of DNA analysis in colorectal carcinoma.
1993
BACKGROUND Reported experiences regarding the prognostic significance of DNA content in colorectal carcinoma have been a matter of controversy. METHODS DNA analysis with image cytometry was performed in 137 patients with colorectal cancer. Only patients who had resection without tumor residual and who did not die postoperatively as a consequence of the operation were entered in the study. At the time of DNA analysis, neither the histomorphologic data nor the relapse-free survival time of the patients were known. RESULTS In this investigation the DNA content of tumor cells had no univariate or multivariate influence on the relapse-free survival time. The prognosis was dependent on the tumor …
EP11.09: Are femur and humerus lengths measured exactly by 3D ultrasound reliable parameters for the detection of Trisomy 21 in the second trimester?
2018
Author response to the contributors to the discussion on “A critical evaluation of the current ‘p -value controversy’”
2017
Establishing Equivalence or Non-Inferiority in Clinical Trials
2012
Background: An increasing number of clinical trials are being performed to show the absence of relevant differences between the effects of two treatments. The primary care physician makes use of the results of so-called equivalence studies, at least indirectly, practically every day. Equally important are active control clinical trials in which the efficacy of a new treatment has to be proven through demonstrating non-inferiority as compared to a standard treatment. Methods: Explanation of basic principles and statistical techniques with reference to the original literature; selective searches in the medical literature. Results: First of all, a suitable distributional parameter must be chos…
Factors influencing survival after resection of pancreatic cancer. A DNA analysis and a histomorphologic study
1994
BACKGROUND The influence of DNA content on prognosis in stomach cancer has been investigated rarely, and the results are controversial. METHOD The prognostic relevance of the DNA content and histomorphologic parameters was evaluated in 41 patients after resection of pancreatic cancer. RESULTS In the univariate analysis, the DNA content, tumor size, lymph node status, tumor stage, nuclear grade, and type of resection had a statistically significant influence on the prognosis. No association was found between the DNA content and the histomorphologic features. Apart from the operative procedure, the DNA content was the strongest indicator of prognosis in the multivariate analysis. CONCLUSIONS …
On easily interpretable multivariate reference regions of rectangular shape
2011
Till now, multivariate reference regions have played only a marginal role in the practice of clinical chemistry and laboratory medicine. The major reason for this fact is that such regions are traditionally determined by means of concentration ellipsoids of multidimensional Gaussian distributions yielding reference limits which do not allow statements about possible outlyingness of measurements taken in specific diagnostic tests from a given patient or subject. As a promising way around this difficulty we propose to construct multivariate reference regions as p-dimensional rectangles or (in the one-sided case) rectangular half-spaces whose edges determine univariate percentile ranges of the…
Prognostisch relevante Faktoren nach kurativer Resektion von Magenkarzinomen unter besonderer Berücksichtigung des DNS-Gehaltes
1992
Bei 103 Patienten wurde nach kurativer Resektion von Magenkarzinomen (Adenokarzinome n = 58, Siegelringzellkarzinome n = 24, undifferenzierte Karzinome n = 21) der Einflus des DNS-Gehaltes der Tumorzellen sowie der ublichen histomorphologischen Beurteilungsparameter auf die Prognose uberpruft. In der multivariaten Regressionsanalyse war die Prognose vom Lymphknotenstatus (p =0,0009), vom pT-Stadium (p = 0,02), von der Tumorlokalisation (p = 0,03) und vom histologischen Typ (p = 0,05) aber nicht vom DNS-Gehalt abhangig. Weiterhin hatten keinen Einflus auf die Prognose der Differenzierungsgrad, das operative Vorgehen, der Sicherheitsabstand, die Tumorgrose, das Geschlecht und das Alter des Pa…
Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study…
1995
A total of 83 patients with nonorgan-confined bladder cancer with or without lymph node metastases (tumor stages pT3b, pT4a and/or pN1, pN2) was evaluated in November 1993 for relapse-free and overall survival. All patients underwent radical cystectomy between 1987 and 1991, 38 underwent adjuvant polychemotherapy with methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC). Of the 83 patients 49 had entered a prospective randomized trial comparing adjuvant to no adjuvant treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognosti…
Advanced Bladder Cancer (Stages pT3b, pT4a, pN1 and pN2): Improved Survival after Radical Cystectomy and 3 Adjuvant Cycles of Chemotherapy. Results o…
1992
A total of 49 bladder cancer patients with tumor stages pT3b, pT4a and/or pelvic lymph node involvement without microscopic or macroscopic evidence of residual tumor was randomized into 2 comparative groups: the chemotherapy group was to receive 3 adjuvant cycles of methotrexate, vinblastine and cisplatin plus doxorubicin (M-VAC) or epirubicin (M-VEC) after radical cystectomy. The control group received no additional treatment. The protocol was activated in May 1987. Patient recruitment was concluded in December 1990 because an interim analysis of the 49 randomized patients revealed a significant prognostic advantage in favor of 26 patients randomized to the chemotherapy group compared to 2…
Nearly exact sample size calculation for powerful non-randomized tests for differences between binomial proportions
2015
In the case of two independent samples, it turns out that among the procedures taken in consideration, BOSCHLOO'S technique of raising the nominal level in the standard conditional test as far as admissible performs best in terms of power against almost all alternatives. The computational burden entailed in exact sample size calculation is comparatively modest for both the uniformly most powerful unbiased randomized and the conservative non-randomized version of the exact Fisher-type test. Computing these values yields a pair of bounds enclosing the exact sample size required for the Boschloo test, and it seems reasonable to replace the exact value with the middle of the corresponding inter…
Analysis of genetic variations of protein tyrosine kinase fyn and their association with alcohol dependence in two independent cohorts.
2003
Abstract Background Decreased sensitivity to and increased tolerance for the effects of alcohol is a phenotype, which was shown to be associated with an increased risk for alcoholism in humans and was observed in protein tyrosine kinase (PTK) fyn knockout mice. Methods We performed an association study of genetic variations of PTK fyn in 430 alcohol-dependent patients and 365 unrelated control subjects from two independent samples. Results In a combined analysis, we found an association of alcohol dependence with the single nucleotide polymorphism (SNP) T137346C in the 5′ untranslated region (UTR) of the gene. A relevant association could be excluded for the remaining two informative SNPs. …
Multivariate equivalence tests for use in pharmaceutical development.
2014
Statistical equivalence analyses are well-established parts of many studies in the biomedical sciences. Also in pharmaceutical development and manufacturing equivalence testing methods are required in order to statistically establish similarities between machines, process components, or complete processes. This article presents a choice of multivariate equivalence testing procedures for normally distributed data as generalizations of existing univariate methods. In all derived methods, variability is interpreted as nuisance parameter. The use of the proposed methods in pharmaceutical development is demonstrated with a comparative analysis of dissolution profiles.
On powerful exact nonrandomized tests for the Poisson two-sample setting.
2020
In the case of two independent samples from Poisson distributions, the natural target parameter for hypothesis testing is the ratio of the two population means. The conditional tests which have been derived for this class of problems already in the 1940s are well known to be optimal in terms of power only when randomized decisions between hypotheses are admitted at the boundary of the respective rejection regions. The major objective of this contribution is to show how the approach used by Boschloo in 1970 for constructing a powerful nonrandomized version of Fisher’s exact test for hypotheses about the odds ratio between two binomial parameters can successfully be adapted for the Poisson c…
A critical evaluation of the current “p-value controversy”
2017
This article has been triggered by the initiative launched in March 2016 by the Board of Directors of the American Statistical Association (ASA) to counteract the current p-value focus of statistical research practices that allegedly "have contributed to a reproducibility crisis in science." It is pointed out that in the very wide field of statistics applied to medicine, many of the problems raised in the ASA statement are not as severe as in the areas the authors may have primarily in mind, although several of them are well-known experts in biostatistics and epidemiology. This is mainly due to the fact that a large proportion of medical research falls under the realm of a well developed bo…
Is the p-Value a Suitable Basis for the Construction of Measures of Evidence? Comment on “The Role of p-Values in Judging the Strength of Evidence an…
2020
Dr. Gibson has to be congratulated for having enriched the wealth of articles written in response to the ASA statement on p-values of 2016 by a valuable and thoughtful contribution. We particularly...
Testing for goodness rather than lack of fit of continuous probability distributions.
2021
The vast majority of testing procedures presented in the literature as goodness-of-fit tests fail to accomplish what the term is promising. Actually, a significant result of such a test indicates that the true distribution underlying the data differs substantially from the assumed model, whereas the true objective is usually to establish that the model fits the data sufficiently well. Meeting that objective requires to carry out a testing procedure for a problem in which the statement that the deviations between model and true distribution are small, plays the role of the alternative hypothesis. Testing procedures of this kind, for which the term tests for equivalence has been coined in sta…
Blood flow velocity waveforms of the fetal middle cerebral artery in a normal population: reference values from 18 weeks to 42 weeks of gestation
2002
The aim of this prospective cross-sectional study was to establish new Doppler reference curves for peak blood flow velocities (Vmax, Vmean, Vmin) and impedance indices (PI, RI) of the middle cerebral artery at 18-42 weeks of gestation by an automatic wave form analysis integrated into the ultrasound device. In 962 low-risk pregnancies, blood flow velocities were derived from the middle cerebral artery with pulsed color Doppler ultrasonography. Reference curves were constructed for the individual parameters based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle for maximum blood flow velocities, as well as on a pol…
SMM900901 Supplemental material - Supplemental material for On powerful exact nonrandomized tests for the Poisson two-sample setting
2020
Supplemental material, SMM900901 Supplemental material for On powerful exact nonrandomized tests for the Poisson two-sample setting by Stefan Wellek in Statistical Methods in Medical Research