bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calibrated phase II clinical trials in oncology
Authors: Herson Jay , Carter Stephen K. 
Published: April 2007

AbstractThis paper proposes the use of calibrated designs in phase II oncological clinical trials and evaluates their statistical properties in terms of power recovery and cost. A calibrated phase II design for a new cancer treatment for a specific tumour, e.g. colo‐rectal, consists of random allocation of patients to receive either the investigational treatment or a standard treatment known to have activity at a certain level in phase II trials (e.g. 5 FU, expected response proportion = 0.20). Patients assigned to the standard treatment form the calibration group. The calibration group is not a control group in the traditional sense and one does not conduct a formal efficacy comparison between the investigational treatment group and the calibration group. Instead, one uses the calibration group to evaluate whether the sample of patients who receive the investigational treatment has the capability of showing a response. If the data do not support the hypothesis that the expected response proportion prevails in the calibration group, one declares the investigational group results suspect and recommends a second trial. Assuming acceptable results of the second trial, we use binomial calculations to find the effect of the calibration design on power recovery and relative cost. We show that when an unrepresentative sample occurs, calibration designs generally recover 90 per cent or more of nominal power at a cost of three to fivefold increase in sample size. We recommend for calibrated phase II trials a ‘master protocol’ approach in which several investigational treatment arms share one concurrent calibration group.
Age, period and cohort models: The use of individual records
Authors: Robertson Chris , Boyle Peter 
Published: April 2007

AbstractProblems with the interpretation of age‐period‐cohort models are dlscussed. If individual records are available as for cancer incidence in Scotland, then a solution is obtainable. An example using incidence data for cancers of the lung and larynx in Scotland is presented to illustrate the models.
Confronting publication bias: A cohort design for meta‐analysis
Authors: Simes Robert John 
Published: April 2007

AbstractIn evaluating therapies, clinical investigators often need to rely on the published clinical trial literature which may be biased in favour of studies with positive or ‘encouraging’ results and this may lead to erroneous conclusions of therapeutic effectiveness. The problem of publication bias can be magnified when the evaluation is based on a pooled analysis of clinical trial results, since in this case even small differences between treatment groups may reach statistical significance.In this paper a model is developed for pooling the results of clinical trials which is free from publication bias. It is proposed that an international registry of all clinical trials be established with the objectives and endpoints of each trial clearly defined in the register. In this way for each therapeutic issue researchers can select a cohort of clinical trials independently from the trial results.The approach is illustrated using the International Cancer Research Data Bank (ICRDB) registry of cancer clinical trials to evaluate the effect of chemotherapy on survival in advanced ovarian cancer. In this example, the conclusions based on a pooled analysis of registered trials have important differences from a more traditional review of the published trials. Implications of the results and problems in implementing the model are discussed.
The role of overviews in cancer therapeutics
Authors: Simon Richard 
Published: April 2007

AbstractThe implications of pooling based overviews for the design and conduct of cancer clinical trials are discussed. Because the results of overviews may be highly publicized and disruptive to ongoing trials, the timing of overviews should be carefully considered. Pooling based overviews can be valuable supplements to major clinical trials if the trials are themselves quite similar in design and quality. Such overviews may be essential for addressing subset questions based on results from such trials. Pooling based overviews are not, however, satisfactory alternatives to major clinical trials. Pooled results of many small dissimilar studies may be misleading with regard to the efficacy of treatments contributing to the average. For toxic cancer treatments, the assumption that unexpected qualitative interactions are unlikely does not provide a satisfactory justification for pooling results of trials that are dissimilar in design or quality of conduct.
Sample size requirements for reliability studies
Authors: Donner Allan , Eliasziw Michael 
Published: April 2007

AbstractThis paper provides exact power contours to guide the planning of reliability studies, where the parameter of interest is the coefficient of intraclass correlation p derived from a one‐way analysis of variance model. The contours display the required numbers of subjects k and number of repeated measurements n that provide 80 per cent power for testing Ho:ρ ⩽ ρo versus H1: ρ > ρo at the 5 per cent level of significance for selected values of po. We discuss the design considerations of these results.
Models for temporal variation in cancer rates. I: Age–period and age–cohort models
Authors: Clayton D. , Schifflers E. 
Published: April 2007

AbstractA main concern of descriptive epidemiologists is the presentation and interpretation of temporal variations in cancer rates. In its simplest form, this problem is that of the analysis of a set of rates arranged in a two‐way table by age group and calendar period. We review the modern approach to the analysis of such data which justifies traditional methods of age standardization in terms of the multiplicative risk model. We discuss the use of this model when the temporal variations are due to purely secular (period) influences and when they are attributable to generational (cohort) influences. Finally we demonstrate the serious difficulties which attend the interpretation of regular trends. The methods described are illustrated by examples for incidence rates of bladder cancer in Birmingham, U.K., mortality from bladder cancer in Italy, and mortality from lung cancer in Belgium.
Some methodological problems in the assessment of complementary therapy
Authors: Anthony Honor M. 
Published: April 2007

AbstractThe increased interest of the public and the medical profession in complementary forms of therapy introduces an urgent need for proper assessment of efficacy. This growth in popularity suggests that complementary therapies are effective in some circumstances, but without objective assessment neither the public nor the medical profession can be sure. Rigorous scientific assessment is required, but the nature of complementary therapy is such that double‐blind randomized controlled trials, as usually conducted, are rarely applicable, and alternative approaches are needed. At its best, complementary therapy is designed individually for each patient, and few treatments can readily be applied ‘blind’. These are the main problems in trial design but complementary therapists are also aware of the importance of body‐mind interactions: they see the ‘placebo effect’ as an integral part of treatment which needs investigation, and they question the validity of clinical trials in which the patient's will is not fully engaged through lack of information, and of those not asking the patients if they feel better. The problems are examined and alternative approaches suggested. The paper raises the question of whether they are only problems for complementary medicine.
The analysis of data from 2 × 2 cross‐over trials with baseline measurements
Authors: Kenward Michael G. , Jones Byron 
Published: April 2007

AbstractAn account is given of the analysis of data from 2 × 2 cross‐over trials which include baseline measurements. We show that most of the previously proposed methods can be incorporated into a general framework of least‐squares estimation with a simple linear model. A simple analysis based on ordinary least‐squares estimators is described which can be used with either two‐sample t‐tests and confidence intervals or with the corresponding non‐parametric procedures. It is shown how the use of generalized least‐squares estimators is equivalent to the use of covariance adjustment. These methods require no assumptions about the covariance structure of the measurements from each subject. The results of assessing the covariance structure present in examples of data from a number of trials are summarized. These results suggest that previously proposed simple covariance structures are unlikely to be appropriate in general.
Confirmatory analysis of survival data using left truncation of the life times of primary survivors
Authors: Keiding Niels , Bayer Thomas , Watt‐Boolsen Steen 
Published: April 2007

AbstractIn survival analysis, as in other branches of applied statistics, confirmatory analysis is often requested before an initial finding can be cleared of suspicion of being due just to mass significance. This paper points out that the special temporal structure of the classical clinical trial with staggered entry allows re‐use of the initial survivors by left‐truncating their remaining survival times. This procedure can often save a considerable amount of calendar time. The procedure is illustrated by data from the Danish Breast Cancer Cooperative Group.
Some points on the use of ‘independent Bayes’ to diagnose acute abdominal pain
Authors: Crichton Nicola J. , Fryer John G. , Spicer Clive C. 
Published: April 2007

AbstractThis paper outlines some of the difficulties encountered when using independent Bayes as a statistical decision aid for acute abdominal pain. Methods of reducing the resultant problems are suggested. Restriction of the number of facets in the system reduces violation of the simplifying assumption of symptom independence without adversely affecting efficiency. Introduction of a realistic utility structure is investigated as is the potential transportability of the decision aid. Generalizations of the results are discussed and potential uses of medical decision aids are considered.
The parameters of death: A consideration of the quantity of information in a life table using a polynomial representation of the survivorship curve
Authors: Anson Jon 
Published: April 2007

AbstractHow much unique information is contained in any life table? The logarithmic survivorship (lx) columns of 360 empirical life tables were fitted by a weighted fifth degree polynomial, and it is shown that six parameters are adequate to reproduce these curves almost flawlessly. However, these parameters are highly intercorrelated, so that a two‐dimensional representation would be adequate to express the similarities and differences among life tables. It is thus concluded that a life table contains but two unique pieces of information, these being the level of mortality in the population which it represents, and the relative shape of the underlying mortality curve.
Exposure—response relationship for a dichotomized response when the continuous underlying variable is not measured
Authors: Irwig L. M. , Groeneveld H. T. 
Published: April 2007

AbstractRadiological assessment of pneumoconiosis is an example of a dichotomized variable, namely one that is analysed as a binary response but in fact has an underlying continuum, which in this case is not measurable. Estimates of exposure—response relationships vary greatly for different observers of a dichotomized response variable because of random error of measurement and differences in the threshold implicitly chosen by each observer for categorizing cases. We present a method of using the biserial correlation coefficient and normal distribution theory to estimate exposure—response relationships at any required threshold for each observer. Exposure—response relationships can also be corrected for random observational error using the reliability coefficient, calculated as the tetrachoric correlation between repeat observations by readers.
Correspondence analysis and logistic modelling: Complementary use in the analysis of a health survey among nurses
Authors: Leclerc A. , Luce D. , Lert F. , Chastang J. F. , Logeay P. 
Published: April 2007

AbstractLogistic or other modelling approaches are often appropriate for studying epidemiological data. However, health surveys may be more complex. With numerous variables, there is a need for exploratory analysis. Parsimonious description of the data is also a useful complement to modelling. Correspondence analysis may be useful in such exploratory phases. An example of the complementary use of the two approaches is presented in the context of a health survey among nurses, which focused on the relationship between shift and night work, and declared health problems.
A statistical methodology for postmarketing surveillance of adverse drug reaction reports
Authors: Norwood Paula K. , Sampson Allan R. 
Published: April 2007

AbstractThis paper presents a statistically optimal exact hypothesis testing procedure for detecting changes in sales adjusted adverse drug reaction (ADR) rates between historical and current periods, with a computer program that implements this test appended. We provide discussions and illustrations on how to monitor ADR rates for product lines that consist of several pharmacologically equivalent dosage forms.
Modelling the 1985 influenza epidemic in France
Authors: Flahault A. , Letrait S. , Blin P. , Hazout S. , Ménarés J. , Valleron A. J. 
Published: April 2007

AbstractThe Rvachev—Baroyan—Longini model is a space—time predictive model of the spread of influenza epidemics. It has been applied to 128 cities of the USSR, and more recently, to forecasting the spread of the pandemic of 1968–1969 throughout 52 large cities. It is a deterministic, mass‐action, space and time continuous model.The model has been applied to the simulation of the influenza epidemic of 1984–1985 in the 22 French Metropolitan districts and results are presented. Estimates of the parameters of the model were made using the French Communicable Diseases Network data. These parameters are the contact rate, a, (estimate = 0.55) which is the number of people with whom an infectious individual will make contact daily sufficient to pass infection and the infectious period, 1/b, estimated as 2.49 days. The mean annual railroad passenger traffic from district i to district j varies from 0 to 1,991,000 persons depending on the districts. The computer spread of the epidemic is presented on weekly maps. Results are also presented on district charts, giving the size of district epidemics and the time of peak of the epidemic. The precision of the computer fittings was judged satisfactory by the calculated size of peak differing from the real one by less than 100 per cent, in 17 out of 18 districts, and by the calculated time of peak differing from the observed by less than two weeks in 14 out of 18 districts. Although precision could be improved with more detailed information about passenger traffic, the French use of the model has been satisfactory.
Toward greater understanding of market orientation and the resource‐based view
Authors: Ketchen David J. , Hult G. Tomas M. , Slater Stanley F. 
Published: April 2007

AbstractConnor's commentary offers a series of thoughtful comments on the ideas presented in Hult, Ketchen, and Slater (2005). We focus on two of his contentions in our response. First, we argue that the theory underlying our study—the resource‐based view—is not tautological. This is because resources and performance are not directly related. Instead, realizing the potential value of resources depends on those resources being exploited through a firm's strategic actions. Second, we disagree with Connor's contention that market‐oriented and customer‐led firms lie along a continuum. We propose a richer conceptualization centered on a two‐by‐two matrix that contains market‐oriented firms, customer‐led firms, and two additional types. Copyright © 2007 John Wiley & Sons, Ltd.
SECCOX, a novel x‐ray characterization bench for Bragg crystals and x‐rays optics
Authors: Caillaud T. , Manson M. , Desenne D. , Goze B. , Rivet A. , Derouineau Ph. 
Published: April 2007

AbstractLaser programs require the use of a large number of calibrated x‐ray crystals implemented inside spectrometers and microscopes used in diagnostics. In this context, a new apparatus was designed in collaboration with CELIA laboratory, Saint‐Gobain Crystals and Detectors and CEA to characterize x‐ray Bragg crystals. Station d'Etude et de Caractérisation des Cristaux pour les Optiques X (SECCOX) is based on a micrometric x‐ray source and an automated spectrometer equipped with a CCD camera. Properties such as homogeneity, resolution, radius of curvature and reflectivity are measured to guarantee diagnostic performance in laser‐plasma physics experiments. We will present the experimental device, techniques and results of the calibration obtained. Copyright © 2007 John Wiley & Sons, Ltd.
Mid‐term Results of Stapled Hemorrhoidopexy for Third‐ and Fourth‐degree Hemorrhoids—Correlation with the Histological Features of the Resected Tissue
Authors: Ohana Gil , Myslovaty Boris , Ariche Arie , Dreznik Zeev , Koren Rumelia , Rath‐Wolfson Lea 
Published: April 2007

AbstractBackgroundStapled hemorrhoidopexy is used to remove a circumferential strip of mucosa and submucosa about 4 cm above the dentate line, in order to restore the correct anatomical relationships of the anal canal structures. We evaluated the histological features of the resected tissue obtained after stapled hemorrhoidopexy with correlation to the short‐term and mid‐term results.MethodsThis retrospective study evaluated 234 cases of stapled hemorrhoidopexy. Data concerning postoperative bleeding, anal pain, incontinence, stenosis, and recurrence of hemorrhoids were collected from hospital and outpatient clinic records. Histologic slides were examined for the type of epithelium, presence of muscle fibers, nerve endings, and degree of vascular ectasia.ResultsSome 52% of the biopsies revealed on the surface a combination of glandular with squamous epithelium, meaning a stapling line at the level of the transitional zone/dentate line. Smooth muscle fibers were more frequent as the stapling line approached the level of the dentate line/transitional zone (p = 0.0028). Internal sphincter fibers were present in 36% of the cases, yet there were no cases of anal incontinence. Inclusion of merely squamous epithelium in the resected tissue correlated with severe postoperative pain persisting one week after surgery (p < 0.0001), whereas the concurrent presence of squamous and glandular epithelium correlated only with severe pain on the first postoperative day (p = 0.018). Nerve endings were more frequent in patients with anal pain one week after surgery (p = 0.02). The rate of recurrence of symptoms was 3%, which did not correlate with any of the histological parameters tested.ConclusionsThough stapled hemorrhoidopexy is performed according to well‐established technical guidelines, it is too difficult to be standardized.
Antihyperalgesic and analgesic properties of the N‐methyl‐d‐aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic hyperalgesia
Authors: Klein Thomas , Magerl Walter , Hanschmann Angelika , Althaus Michael , Treede Rolf‐Detlef 
Published: April 2007

AbstractNMDA‐receptors are a major target in the prevention and treatment of hyperalgesic pain states in neuropathic pain. However, previous studies revealed equivocal results depending on study design and efficacy parameters.We tested the analgesic (generalized reduction of generation and processing of nociceptive signalling) and anti‐hyperalgesic (prevention of central sensitization) properties of the NMDA‐receptor antagonist neramexane and the potassium channel opener flupirtine in the intradermal capsaicin injection model. Furthermore, we tested the effect on pain summation (wind up). Eighteen healthy subjects received either a single dose of neramexane (40mg p.o.), flupirtine (100mg) or placebo in a double‐blind, randomized, cross‐over study.Pain evoked by intradermal capsaicin injection as well as pain evoked by pinpricks was significantly reduced by neramexane (−22% to −30% vs. placebo) in the non‐sensitized skin indicating a marked analgesic effect. Moreover, dynamic mechanical allodynia (pain to light touch) was also significantly attenuated by neramexane (−28% vs. placebo). However, static secondary hyperalgesia to pinprick stimuli after capsaicin injection was not significantly reduced (−9% vs. placebo). Flupirtine showed no analgesic or anti‐hyperalgesic effect. Mechanically‐evoked wind up of pain sensation was not affected by any treatment.The results suggests that in a human surrogate model of neurogenic hyperalgesia a single low‐dose of neramexane had a marked analgesic effect in the sensitized and in the non‐sensitized state and thus may be a useful drug to treat the enhanced pain sensitivity in neuropathic pain patients. Its efficacy may be based on analgesia rather than anti‐hyperalgesia or anti‐windup. In contrast, flupirtine showed neither an analgesic nor an anti‐hyperalgesic effect at a dose used for the treatment of postoperative pain.
An estimate of the total worldwide societal costs of dementia in 2005
Authors: Wimo Anders , Winblad Bengt , Jönsson Linus 
Published: April 2007

BackgroundThe aim of this report was to estimate the worldwide cost of dementia in 2005 from a societal viewpoint.MethodsCosts were estimated by combining prevalence estimates, country and region specific data on Gross Domestic Product per person, and average wage with results from previously published cost‐of‐illness studies in different countries. Direct medical and nonmedical costs as well as costs for informal care were included.ResultsThe total worldwide societal cost of dementia, on the basis of a dementia population of 29.3 million persons, was estimated to be US$315.4 billion in 2005, including US$105 billion for informal care (33%). Seventy‐seven percent of the total costs occurred in the more developed regions, with 46% of the prevalence.ConclusionsWorldwide costs for dementia are enormous, and informal care constitutes a major cost component, in particular in less developed regions. The health economics of dementia is a highly relevant area for further research.